Clinical Neurologic and Developmental Studies after Cardiac Surgery Utilizing Hypothermic Circulatory Arrest and Cardiopulmonary Bypass

  • Gil Wernovsky
  • Richard A. Jonas
  • Paul R. Hickey
  • Adre J. du Plessis
  • Jane W. Newburger
Part of the Developments in Critical Care Medicine and Anesthesiology book series (DCCA, volume 31)


The dramatic reduction in surgical mortality associated with repair of congenital heart anomalies in recent decades has been accompanied by a growing recognition of adverse neurologic sequelae in some survivors. Central nervous system (CNS) abnormalities may be a function of coexisting brain abnormalities (1, 2) or acquired events unrelated to surgical management (e.g., paradoxical embolus, brain infection, effects of chronic cyanosis) (3), but CNS insults appear to occur most frequently during or immediately after surgery. In particular, support techniques used during neonatal and infant cardiac surgery—cardiopulmonary bypass (CPB), profound hypothermia and circulatory arrest—have been implicated as important causes of brain injury. This paper will review the effects of CPB and deep hypothermic circulatory arrest (DHCA) on neurodevelopmental outcome.


Cardiopulmonary Bypass Intelligence Quotient Circulatory Arrest Arterial Switch Operation Neonatal Seizure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Berthrong M, Sabiston DC: Cerebral lesions in congenital heart disease: A review of autopsies on one hundred and sixty-two cases. Bull John Hopkins Hospital 89:384–401, 1951Google Scholar
  2. 2.
    Glauser TA, Rorke LB, Weinberg PM, Clancy RR: Congenital brain anomalies associated with the hypoplastic left heart syndrome. Pediatrics 85:984–990, 1990PubMedGoogle Scholar
  3. 3.
    Terplan KL: Patterns of brain damage in infants and children with congenital heart disease. AJDC 125:175, 1973Google Scholar
  4. 4.
    Slogoff ST, Girgis KZ, Keats AS: Etiologic factors in neuro-psychiatric complications associated with cardiopulmonary bypass. Anesth Analg 61:903–911, 1982PubMedCrossRefGoogle Scholar
  5. 5.
    Bellinger DC, Wernovsky G, Rappaport LA, et al: Cognitive development of children following early repair of transposition of the great arteries using deep hypothermic circulatory arrest. Pediatrics 87:701–707, 1991PubMedGoogle Scholar
  6. 6.
    Watanabe T, Masamichi M, Orito H, Kobayasi M, Washio M: Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg 100:274–280, 1990PubMedGoogle Scholar
  7. 7.
    Watanabe T, Miura M, Inui K, et al: Blood and brain tissue gaseous strategy for profoundly hypothermic total circulatory arrest. J Thorac Cardiovasc Surg 102:497–504, 1991PubMedGoogle Scholar
  8. 8.
    Johnston WE, Vinten-Johansen J, DeWitt DS, O’Steen WK, Stump DA, Prough DS: Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension. Ann Thorac Surg 52:479–489, 1991PubMedCrossRefGoogle Scholar
  9. 9.
    Willford DC, Moores WY, Ji S, Zhung TC, Palencia A, Daily PO: Importance of acid-base strategy in reducing myocardial and whole body oxygen consumption during perfusion hypothermia. J Thorac Cardiovasc Surg 100:699–707, 1990PubMedGoogle Scholar
  10. 10.
    Jonas RA, Newburger JW, Wernovsky G, Farrell DM, Rappaport LA, Bellinger DC: Alkaline pH strategy during core cooling worsens developmental outcome after circulatory arrest. Circulation 84 (suppl 11):121A, 1991Google Scholar
  11. 11.
    Settergren G, Ohqvist G, Lundberg S, et al: Cerebral blood flow and cerebral metabolism in children following cardiac surgery with deep hypothermia and circulatory arrest. Clinical course and follow-up of psychomotor development. Scan J Thor CV Surg 16:209–215, 1982Google Scholar
  12. 12.
    Wright JS, Hicks RG, Newman DC: Deep hypothermic arrest: observations on later development in children. J Thorac Cardiovasc Surg 77:466–468, 1979PubMedGoogle Scholar
  13. 13.
    Wells FC, Coghill S, Caplan HL, Lincoln C: Duration of circulatory arrest does influence the psychological development of children after cardiac operation in early life. J Thorac Cardiovasc Surg 86:823–831, 1983PubMedGoogle Scholar
  14. 14.
    Muraoka R, Yokota M, Aoshima M, et al: Subclinical changes in brain morphology following cardiac operations as reflected by computed tomographic scans of the brain. J Thorac Cardiovasc Surg 81:364–369, 1981PubMedGoogle Scholar
  15. 15.
    Fisk GC, Wright JS, Hicks RG, et al: The influence of duration of circulatory arrest at 20OC on cerebral changes. Anaesth Intens Care 4:126–134, 1976Google Scholar
  16. 16.
    Jonas RA, Wernovsky G, Ware J, et al: The Boston circulatory arrest study: perioperative neurologic outcome after the arterial switch operation. Circulation 86 (suppl 1):360A, 1992Google Scholar
  17. 17.
    Barry YA, Labow RS, Keon WJ, Tocchi M, Rock G: Perioperative exposure to plasticizers in patients undergoing cardiopulmonary bypass. J Thorac Cardiovasc Surg 97:900–905, 1989PubMedGoogle Scholar
  18. 18.
    Blauth CI, Smith PL, Arnold JV, Jagoe JR, Wootton R, Taylor KM: Influence of oxygenator type on the prevalence and extent of mircroembolic retinal ischemia during cardiopulmonary bypass. J Thorac Cardiovasc Surg 99:61–69, 1990PubMedGoogle Scholar
  19. 19.
    Fish KJ: Microembolization: etiology and prevention. In: Hilberman M, ed. Brain injury and protection during heart surgery. Boston: Martinus Nijhoff Publishing, 1988, pp 67–84Google Scholar
  20. 20.
    Nussmeier MA, McDermott JP: Macroembolization: prevention and outcome modification. In: Hilberman M, ed. Brain injury and protection during heart surgery. Boston: Martinus Nijhoff Publishing, 1988, pp 85–108Google Scholar
  21. 21.
    Padayachee TS, Parsons S, Theobold R, Gosling RG, Deverall PB: The effect of arterial filtration on reduction of gaseous microemboli in the middle cerebral artery during cardiopulmonary bypass. Ann Thorac Surg 45:647–649, 1988PubMedCrossRefGoogle Scholar
  22. 22.
    Wilson GJ, Rebeyka IM, Coles JG, et al: Loss of the somatosensory evoked response as an indicator of reversible cerebral ischemia during hypothermic, low-flow cardiopulmonary bypass. Ann Thorac Surg 45:206–209, 1988PubMedCrossRefGoogle Scholar
  23. 23.
    Kern FH, Jonas RA, Mayer JE, et al: Temperature monitoring during CPB in infants: does it predict efficient brain cooling? Ann Thorac Surg 54:749–754, 1992PubMedCrossRefGoogle Scholar
  24. 24.
    Coselli JS, Crawford ES, Beall AC, Mizrahi EM, Hess KR, Patel VM: Determination of brain temperatures for safe circulatory arrest during cardiovascular operation. Ann Thorac Surg 45:638–642, 1988PubMedCrossRefGoogle Scholar
  25. 25.
    Busto R, Dietrich WD, Globus MYT, et al: Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J Cerbrl Blood Flow and Met 7:729–738, 1987CrossRefGoogle Scholar
  26. 26.
    Pulsinelli WA, Waldman S, Rawlinson D, Plum F: Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. Neur 32:1239, 1982Google Scholar
  27. 27.
    Steward DJ, DaSilva CA, Flegel T: Elevated blood glucose levels may increase the danger of neurological deficit following profoundly hypothermic cardiac arrest. Anesth 68:653, 1988CrossRefGoogle Scholar
  28. 28.
    Whitman V, Drotar D, Lambert S, et al: Effects of cardiac surgery with extracorporeal circulation on intellectual function in children. Circulation 160–163, 1973Google Scholar
  29. 29.
    Hammeke TA, Hastings JE: Neuropsychologic alterations after cardiac operation. J Thorac Cardiovasc Surg 96:326–331, 1989Google Scholar
  30. 30.
    Grote CL, Shanahan PT, Salmon P, et al: Cognitive outcome after cardiac operations. J Thorac Cardiovasc Surg 104:1405–1409, 1992PubMedGoogle Scholar
  31. 31.
    Aberg T: Cerebral injury during open heart surgery: studies using functional, biochemical, and morphological methods. In: Hilberman M, ed. Brain injury and protection during heart surgery. Boston: Martinus Nijhoff Publishing, 1988, pp 1–12Google Scholar
  32. 32.
    Kirklin JK, Westaby S, Blackstone EH, et al: Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 86:845–857, 1983PubMedGoogle Scholar
  33. 33.
    Jonas RA: Pathophysiology of cardiopulmonary bypass and its relation to age: metabolic response. In: Jonas RA, Elliott ME, eds. Cardiopulmonary Bypass for Neonates, Infants and Small Children. London: Butterworth-Heinemann, 1993Google Scholar
  34. 34.
    Mathews K, Bale JF, Clark EB, et al: Cerebral infarction complicating Fontan surgery for cyanotic congenital heart disease. Petitur Cartel 7:161–166, 1986Google Scholar
  35. 35.
    McConnell JR, Fleming W, Chi W-K, et al: Magnetic resonance imaging of the brain in infants and children before and after cardiac surgery. A prospective study. AJDC 144:374–378, 1990PubMedGoogle Scholar
  36. 36.
    Moody DM, Belal MA, Calla VR, Johnston WE, Prough DS: Brain microemboli during cardiac surgery or aortography. Ann Neurol 28:477–486, 1990PubMedCrossRefGoogle Scholar
  37. 37.
    Ekroth R, Thompson RJ, Lincoln C, Scallan M, Rossi R, Tsang V: Elective deep hypothermia with total circulatory arrest: changes in plasma creatine kinase BB, blood glucose, and clinical variables. J Thorac Cardiovasc Surg 97:30–35, 1989PubMedGoogle Scholar
  38. 38.
    Mezrow CK, Sadeghi AM, Gandsas A, et al: Cerebral blood flow and metabolism in hypothermic circulatory arrest. Ann Thorac Surg 54:609–616, 1992PubMedCrossRefGoogle Scholar
  39. 39.
    Greeley WJ, Kern FH, Ungerleider RM, et al: The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants and children. J Thorac Cardiovasc Surg 101:783–794, 1991PubMedGoogle Scholar
  40. 40.
    Lundar T, Lindberg H, Lindegaard KF, et al: Cerebral Perfusion during Major Cardiac Surgery in Children. Pediatric Cardiology 8:161–65, 1987PubMedCrossRefGoogle Scholar
  41. 41.
    Greely W, Ungerleider RM, Smith LR, Reves JG: The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children. J Thorac Cardiovasc Surg 97:737–745, 1989Google Scholar
  42. 42.
    Greeley WJ, Ungerleider RM, Kern FH, et al: Effects of cardiopulmonary bypass on cerebral blood flow in neonates, infants, and children. Circulation 80:209–215, 1989Google Scholar
  43. 43.
    Soma Y, Hirotani T, Yozu R, et al: A clinical study of cerebral circulation during extracorporeal circulation. J Thorac Cardiovasc Surg 97:187–193, 1989PubMedGoogle Scholar
  44. 44.
    Kern FH, Ungerleider RM, Quill TJ, et al: Cerebral blood flow response to changes in arterial carbon dioxide tension during hypothermic cardiopulmonary bypass in children. J Thorac Cardiovasc Surg 101:618–622, 1991PubMedGoogle Scholar
  45. 45.
    Mault JR, Ohtake S, Klingensmith ME, et al: Cerebral metabolism and circulatory arrest: effects of duration and strategies for protection. Ann Thorac Surg 55:57–64, 1993PubMedCrossRefGoogle Scholar
  46. 46.
    Folkerth TL, Angell WW, Fosburg RG, Oury JH: Effect of deep hypothermia, limited cardiopulmonary bypass, and total arrest on growing puppies. In: Recent advances in studies on cardiac structure, Vol. 10. Baltimore: University Park, 1975, pp 411–421Google Scholar
  47. 47.
    Kramer RS, Sanders AP, Lesage AM, Woodhall B, Sealy WC: The effect of profound hypothermia on preservation of cerebral ATP content during circulatory arrest. J Thorac Cardiovasc Surg 56:699, 1968PubMedGoogle Scholar
  48. 48.
    Fisk GC, Wright JS, Turner BB: Cerebral effects of circulatory arrest at 200 C in the infant pig. Anaesth Intens Care 2:33, 1974Google Scholar
  49. 49.
    Wolin LR, Massopust LC Jr, White RJ: Behavioral effects of autocerebral perfusion, hypothermia and arrest of cerebral blood flow in the rhesus monkey. Exp Neurol 39:336, 1973PubMedCrossRefGoogle Scholar
  50. 50.
    Treasure T, Naftel DC, Conger KA, Garcia JH, Kirklin JW, Blackstone EH: The effect of hypothermic circulatory arrest time on cerebral function, morphology, and biochemistry. J Thorac Cardiovasc Surg 86:761, 1983PubMedGoogle Scholar
  51. 51.
    Coles JG, Taylor MJ, Pearce JM, et al: Cerebral monitoring of somatosensory evoked potentials durinq profoundly hypothermic circulatory arrest. Circulation 70 (suppl): 1-96–1-102, 1984CrossRefGoogle Scholar
  52. 52.
    Weiss M, Weiss J, Cotton J, Nicolas F, Binet JP: A study of the electroencephalogram during surgery with deep hypothermia and circulatory arrest in infants. J Thorac Cardiovasc Surg 70:316–329, 1975PubMedGoogle Scholar
  53. 53.
    Rossi R, Ekroth R, Lincoln C, et al: Detection of cerebral injury after total circulatory arrest and profound hypothermia by estimation of specific creatinine kinase isoenzyme levels using monoclonal antibody techniques. Am J Cartel 58:1236–1241, 1986CrossRefGoogle Scholar
  54. 54.
    Hicks RG, Poole JL: Electroencephalographic changes with hypothermia and cardiopulmonary bypass in children. J Thorac Cardiovasc Surg 81:781–786, 1992Google Scholar
  55. 55.
    Nussmeier NA, Arlund C, Slogoff ST: Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate. Anesth 64:165–170, 1986CrossRefGoogle Scholar
  56. 56.
    Shewmon DA: What is a neonatal seizure? Problems in definition and quantification for investigative and clinical purposes. J Clin Neurophysiol 7:315–368, 1993Google Scholar
  57. 57.
    Volpe JJ: Neonatal seizures: current concepts and revised classification. Pediatrics 84:422–428, 1989PubMedGoogle Scholar
  58. 58.
    Scher MS, Painter MJ: Controversies concerning neonatal seizures. Ped Clncs of NA 36:281–310, 1989Google Scholar
  59. 59.
    Zelnik N, Nir A, Amit S, lancu TC: Autonomic seizures in an infant: unusual cutaneous and cardiac manifestations. Dev Med Child Neurol 32:74–78, 1990PubMedCrossRefGoogle Scholar
  60. 60.
    Clancy RR, Legido A, Lewis D: Occult neonatal seizures. Epilepsia 29:256–261, 1988PubMedCrossRefGoogle Scholar
  61. 61.
    Ehyai A, Fenichel GM, Bender HWJr: Incidence and prognosis of seizures in infants after cardiac surgery with profound hypothermia and circulatory arrest. JAMA 252:3165–3167, 1984PubMedCrossRefGoogle Scholar
  62. 62.
    Wernovsky G, Jonas RA, Newburger JW, et al: The Boston circulatory arrest study: hemodynamics and hospital course after the arterial switch operation. Circulation 86 (suppl 1):237A, 1992Google Scholar
  63. 63.
    Brunberg JA, Really EL, Doty DB: Central nervous system consequences in infants of cardiac surgery using deep hypothermia and circulatory arrest. Circulation 50 (suppl 11):60–68, 1974Google Scholar
  64. 64.
    Barratt-Bodes BG: Choreoathetosis as a complication of cardiopulmonary bypass. Ann Thorac Surg 50:693–694, 1990CrossRefGoogle Scholar
  65. 65.
    Robinson RO, Samuels M, Pohl KRE: Choreic syndrome after cardiac surgery. Arch Dis Child 63:1466–1469, 1988PubMedCrossRefGoogle Scholar
  66. 66.
    Smith-Wical B, Tomasi LG: A distinctive neurologic syndrome after induced profound hypothermia. Pediatric Neurol 6:202–205, 1990CrossRefGoogle Scholar
  67. 67.
    Brunberg JA, Doty DB, Really EL: Choreoathetosis in infants following cardiac surgery with deep hypothermia and circulatory arrest. J Petitur 84:232–235, 1974Google Scholar
  68. 68.
    Chaves E, Scaltsas-Persson l: Severe choreoathetosis following congenital heart disease surgery. Neur 38 (suppl):284, 1988Google Scholar
  69. 69.
    DeLeon S, llbawi M, Archiia R, et al: Choreoathetosis after deep hypothermia without circulatory arrest. Ann Thorac Surg 50:714–719, 1990PubMedCrossRefGoogle Scholar
  70. 70.
    Treasure T: The safe duration of total circulatory arrest with profound hypothermia. Am Heart J 1991Google Scholar
  71. 71.
    Wong PC, Barlow CF, Hickey PR, et al: Factors associated with choreoathetosis after cardiopulmonary bypass in children with congenital heart disease. Circulation 86 (suppl 11):118–126, 1992Google Scholar
  72. 72.
    Messmer BJ, Schallberger U, Gattiker R, Senning A: Psychomotor and intellectual development after deep hypothermia and circulatory arret in early infancy. J Thorac Cardiovasc Surg 72:495–502, 1976PubMedGoogle Scholar
  73. 73.
    Haka-lkse K, Blackwood MJA, Steward DJ: Psychomotor development of infants and children after profound hypothermia during surgery for congenital heart disease. Develop Med Child Neurol 20:62–70, 1978CrossRefGoogle Scholar
  74. 74.
    Dickinson DF, Sambrooks JE: Intellectual performance in children after circulatory arrest with profound hypothermia in infancy. Arch Dis Child 54:1–6, 1979PubMedCrossRefGoogle Scholar
  75. 75.
    Clarkson PM, MacArthur BA, Bard-Bodes BG, Whitlock RM, Neutze JM: Developmental progress after cardiac surgery in infancy using hypothermia and circulatory arrest. Circulation 62:855–861, 1980PubMedGoogle Scholar
  76. 76.
    Blackwood MJA, Haka-lkse K, Steward DJ: Developmental outcome in children undergoing surgery with profound hypothermia. Anesth 65:437–440, 1986CrossRefGoogle Scholar
  77. 77.
    Ferry PC: Neurologic sequelae of open-heart surgery in children: an “irritating question”. AJDC 144:369–373, 1990PubMedGoogle Scholar
  78. 78.
    Sotaniemi KA: Cerebral outcome after extracorporeal circulation. Comparison between prospective and retrospective evaluations. Arch Neurol 40:75–77, 1989Google Scholar
  79. 79.
    Kern FH, Ungerleider RM, Schulman S, et al: Comparison of two strategies of CPB cooling on jugular venous oxygen saturation. Anesth 77:1136A, 1992CrossRefGoogle Scholar
  80. 80.
    Baraka AS, Baroody MA, Haroun ST, et al: Effect of alpha stat versus pH stat strategy on oxyhemoglobin dissociation and whole-body oxygen consumption during hypothermic cardiopulmonary bypass. Anesth Analg 74:32–37, 1992PubMedCrossRefGoogle Scholar
  81. 81.
    Rogers AT, Prough DS, Roy RC, et al: Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man. J Thorac Cardiovasc Surg 103:363–368, 1992PubMedGoogle Scholar
  82. 82.
    Tuppurainen T, Settergren G, Stensved P: The effect of arterial pH on whole body oxygen uptake during hypothermic cardiopulmonary bypass in man. J Thorac Cardiovasc Surg 98:769–773, 1989PubMedGoogle Scholar
  83. 83.
    Murkin JM: Cerebral hyperperfusion during cardiopulmonary bypass: the influence of PaCO2- In: Hilberman M, ed. Brain injury and protection during heart surgery. Boston: Martinus Nijhoff Publishing, 1988, pp 47–66Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Gil Wernovsky
  • Richard A. Jonas
  • Paul R. Hickey
  • Adre J. du Plessis
  • Jane W. Newburger

There are no affiliations available

Personalised recommendations