Modifiable Factors During Cardiopulmonary Bypass in Children and Neonates: What Predicts Early-Onset Neurocomplications After Cardiac Surgery?

Document Type: Original Article

Authors

1 Department of Pediatric Neurology, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, IR Iran.

2 Department of Pediatric Cardiac Surgery, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, IR Iran.

3 Department of Pediatric Cardiology, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, IR Iran.

4 Department of Pediatric Cardiology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.

Abstract

Background: Despite the great progress in the surgery of complex congenital heart diseases, there is still concern regarding adverse neurological events. We aimed to determine the pre- and on-pump modifiable factors that could predict the neurocomplications after pediatric cardiac surgery.
Methods: In a prospective study, modifiable factors such as arterial blood gas, serum lactate, serum glucose, mean arterial pressure, and nasopharyngeal temperature were measured before and during cardiopulmonary bypass (CPB). Moreover, the CPB time, the aortic cross-clamp time, and the deep hypothermic circulatory arrest time were recorded. If there were adverse neurological complications, brain computed tomography scan was done.
Results: From 435 patients with congenital heart diseases that underwent cardiac surgery, 364 patients at a mean age of 22 months were enrolled in the study. Thirty-three (9%) patients had adverse early-onset neurological events. Seizure and hemorrhage were the most common clinical and neuroimaging findings, respectively. Although the pre-pump oxygen saturation (P = 0.03), the blood CO2 level (P = 0.04), and the serum glucose level (P = 0.03) showed statistical significance in the univariate analysis, the only predictive variables of neurocomplications in the multivariate analysis of logistic regression were the on-pump serum glucose level (P = 0.001) and the nasopharyngeal temperature (P = 0.004).
Conclusions: Among several modifiable factors exerting an influence on the neurological outcome of children undergoing cardiac surgery, special attention should be paid to the control of the intraoperative serum glucose level and the provision of the optimal cooling temperature. (Iranian Heart Journal 2020; 21(2): 48-56)

Keywords


1. Aberg T, Kihlgren M. Cerebral protection during open-heart surgery. Thorax. 1977; 32(5): 525-33.
2. Laussen PC. Neonates with congenital heart disease. Curr Opin Pediatr. 2001; 13(3): 220-6.
3. Cooley DA. Early development of congenital heart surgery: open heart procedures. Ann Thorac Surg. 1997; 64(5): 1544-8.
4. Branthwaite MA. Prevention of neurological damage during open-heart surgery. Thorax. 1975; 30(3): 258-61.
5. Russell RW, Bharucha N. The recognition and prevention of border zone cerebral ischaemia during cardiac surgery. Q J Med. 1978; 47(3): 303-23.
6. Arrowsmith JE, Grocott HP, Reves JG, Newman MF. Central nervous system complications of cardiac surgery. Br J Anaesth. 2000; 84(3): 378-93.
7. Menache CC, du Plessis AJ, Wessel DL, Jonas RA, Newburger JW. Current incidence of acute neurologic complications after open-heart operations in children. Ann Thorac Surg. 2002; 73(6): 1752-8.
8. Sotaniemi KA. Brain damage and neurological outcome after open-heart surgery. J Neurol Neurosurg Psychiatry. 1980; 43(2): 127-35.
9. Hsia TY, Gruber PJ. Factors influencing neurologic outcome after neonatalcardiopulmonary bypass: what we can and cannot control. Ann Thorac Surg. 2006; 81(6):S2381-8.
10. Ehyai A, Fenichel GM, Bender HW Jr. Incidence and prognosis of seizures in infants after cardiac surgery with profound hypothermia and circulatory arrest. JAMA. 1984; 252: 3165-7.
11. Ferry PC. Neurologic sequelae of open-heart surgery in children. An 'irritating question'. Am J Dis Child. 1990;144(3): 369-73.
12. Miller G, Eggli KD, Contant C, Baylen BG, Myers JL. Postoperative neurologic complications after open heart surgery on young infants. Arch Pediatr Adolesc Med. 1995; 149(7): 764-8.
13. Fallon P, Aparício JM, Elliott MJ, Kirkham FJ. Incidence of neurological complications of surgery for congenital heart disease. Arch Dis Child. 1995; 72(5): 418-22.
14. Bellinger DC, Wypij D, Kuban KC, et al. Developmental and neurological status of children at 4 years of age after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. Circulation. 1999; 100(5): 526-32.
15. Pérez-Vela JL, Ramos-González A, López-Almodóvar LF, et al. Neurologic complications in the immediate postoperative period after cardiac surgery. Role of brain magnetic resonance imaging. Rev Esp Cardiol. 2005; 58(9): 1014-21.
16. Wong PC, Barlow CF, Hickey PR, et al. Factors associated with choreoathetosis after cardiopulmonary bypass in children with congenital heart disease Circulation. 1992; 86(5 Suppl): 18-26.
17. Trittenwein G, Nardi A, Pansi H, et al. Early postoperative prediction of cerebral damage after pediatric cardiac surgery. Ann Thorac Surg. 2003; 76(2): 576-80.
18. Dominguez TE, Wernovsky G, Gaynor JW. Cause and prevention of central nervous system injury in neonates undergoing cardiac surgery. Semin Thorac Cardiovasc Surg. 2007;19:269-77.
19. Doenst T, Wijeysundera D, Karkouti K, et al. Hyperglycemia during cardiopulmonary bypass is an independent risk factor for mortality in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2005; 130(4):1144.
20. Duncan AE . Hyperglycemia and perioperative glucose management. Curr Pharm Des. 2012; 18(38):6195-203.
21. Huang MT, Lee CF, Dobson GP. Epinephrine enhances glycogen turnover and depresses glucose uptake in vivo in rat heart. FASEBJ. 1997; 11(12):973–80.
22. Lee KU, Lee HK, Koh CS, Min HK. Artificial induction of intravascular lipolysis by lipid-heparin infusion leads to insulin resistance in man. Diabetologia. 1988; 31(5): 285–90.
23. Wittnich C, Dewar ML, Chiu RC. Myocardial protection: heparin induced free fatty acid elevation during cardiopulmonary bypass andits prevention. J Surg Res. 1984; 36(6): 527–31.
24. Hotamisligil GS, Shargill N, Spiegelman BM. Adipose Expression of tumor necrosis factor alpha: direct role in obesity-linked insulin resistance. Science.1993; 259(5091): 87-91.
25. Davies MG, Hagen PO. Alterations in venous endothelial cell and smooth muscle cell relaxation induced by high glucose concentrations can be prevented by aminoguanidine. J Surg Res. 1996 1; 63(2): 474-9.
26. Li PA, Siesjö BK. Role of hyperglycaemia-related acidosis in ischaemic brain damage. Acta Physiol Scand. 1997; 161(4): 567-80.
27. Kawai N, Stummer W, Ennis SR, Betz AL, Keep RF. Blood-brain barrier glutamine transport during normoglycemic and hyperglycemic focal cerebral ischemia. J Cereb Blood Flow Metab. 1999; 19(1): 79-86.
28. Alvarez-Sabín, J., Molina, C. A., Montaner, J., Arenillas, J. F., Huertas, R., Ribo, M., et al. (2003). Effects of admission hyperglycemia on stroke outcome in reperfused tissue plasminogen activator-treated patients. Stroke, 34, 1235–1241.
29. Parsons, M. W., Barber, P. A., Desmond, P. M., Baird, T. A., Darby, D.G., Byrnes, G., et al. (2002). Acute hyperglycemia adversely affects stroke outcome: A magnetic resonance imaging and spectroscopy study. Annals of Neurology, 52, 20–28.
30. Song, E., Chu, K., Jeong, S., Jung, K., Kim, S., Kim, M., et al. (2003). Hyperglycemia exacerbates brain edema and perihematomal cell death after intracerebral hemorrhage. Stroke, 34, 215–2220.
31. Capes, S., Hunt, D., Malmberg, K., Pathak, P., & Gerstein, H. (2001). Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: A systemic overview. Stroke, 32, 2426–2432.
32. Krinsley, J. (2003). Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. Mayo Clinic Proceedings, 78(, 1471–1478.
33. Mora CT, Henson MB, Weintraub WS, et al. The effect of temperature management during cardiopulmonary bypass on neurologic and
neuropsychologic outcomes in patients undergoing coronary revascularization. J Thorac Cardiovasc Surg. 1996; 112(2): 514-22.
34. Michenfelder JD. The hypothermic brain in Anesthesia and the brain. New York, Churchill Livingstone; 1988: 23-34.
35. Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neurotoxicity in cortical cell culture. J Neurosci. 1987; 7(2): 357-68.
36. Small DL, Morley P, Buchan AM. Biology of ischemic cerebral cell death.Prog Cardiovasc Dis. 1999; 42(3): 185-207 9.
37. Schaller B, Graf R.Hypothermia and stroke: the pathophysiological background. Pathophysiology. 2003; 10(1): 7-35.
38. Ma H, Sinha B, Pandya RS, et al. Therapeutic hypothermia as a neuroprotective strategy in neonatal hypoxic-ischemic brain injury and traumatic brain injury. Curr Mol Med. 2012; 12(10): 1282-96.
39. Perlman JM. Intervention strategies for neonatal hypoxic-ischemic cerebral injury. Clin Ther. 2006; 28(9): 1353-65.
40. Jiang JY, Xu W, Li WP, et al. Effect of long-term mild hypothermia or short-term mild hypothermia on outcome of patients with severe traumatic brain injury. J Cereb Blood Flow Metab. 2006 Jun. 26 (6):771-6.
41. Horn CM, Sun CH, Nogueira RG, et al. Endovascular reperfusion and cooling in cerebral acute ischemia (ReCCLAIM I). J Neurointerv Surg. 2014 Mar. 6 (2):91-5.
42. Battin MR, Penrice J, Gunn TR, Gunn AJ. Treatment of term infants with head cooling and mild systemic hypothermia (35.0 degrees C and 34.5 degrees C) after perinatal asphyxia. Pediatrics. 2003 Feb. 111 (2):244-51.
43. Negovsky VA. Postresuscitation disease. Crit Care Med. 1988 Oct. 16 (10):942-6.
44. Seltzer L, Swartz MF, Kwon J, et al. Neurodevelopmental outcomes after neonatal cardiac surgery: Role of cortical isoelectric activity. J Thorac Cardiovasc Surg. 2016; 151(4): 1137-42.