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• W1986306295 abstract "Deep hypothermic circulatory arrest (DHCA) has been used for the past 50 years in the surgical repair of complex congenital cardiac malformations and operations involving the aortic arch; it enables the surgeon to achieve precise anatomical reconstructions by creating a bloodless operative field. Nevertheless, DHCA has been associated with immediate and late neurodevelopmental morbidities. This review provides an overview of the pathophysiology of neonatal hypoxic brain injury after DHCA, focusing on cellular mechanisms of necrosis, apoptosis, and glutamate excitotoxicity. Techniques and strategies in neonatal brain protection include hypothermia, acid base blood gas management during cooling, and pharmacologic interventions such as the use of volatile anesthetics. Surgical techniques consist of intermittent cerebral perfusion during periods of circulatory arrest and continuous regional brain perfusion. Deep hypothermic circulatory arrest (DHCA) has been used for the past 50 years in the surgical repair of complex congenital cardiac malformations and operations involving the aortic arch; it enables the surgeon to achieve precise anatomical reconstructions by creating a bloodless operative field. Nevertheless, DHCA has been associated with immediate and late neurodevelopmental morbidities. This review provides an overview of the pathophysiology of neonatal hypoxic brain injury after DHCA, focusing on cellular mechanisms of necrosis, apoptosis, and glutamate excitotoxicity. Techniques and strategies in neonatal brain protection include hypothermia, acid base blood gas management during cooling, and pharmacologic interventions such as the use of volatile anesthetics. Surgical techniques consist of intermittent cerebral perfusion during periods of circulatory arrest and continuous regional brain perfusion. Since its introduction in the 1940s, deep hypothermic circulatory arrest (DHCA) has facilitated complex cardiac surgery, especially in very small patients. At that time, technical expertise and cardiopulmonary bypass hardware were such that there was no safe alternative. The use of DHCA enabled the surgeon to attain a bloodless operative field, so that precise anatomical reconstruction could be achieved. However, DHCA turned out to be a double-edged sword: on the one hand, surgical results were markedly improved, but on the other, the use of DHCA has been associated with immediate and late neurodevelopmental morbidities [1Newburger J.W. Jonas R.A. Wernovsky G. et al.A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery.N Engl J Med. 1993; 329: 1057-1064Crossref PubMed Scopus (592) Google Scholar, 2Bellinger D.C. Jonas R.A. Rappaport L.A. et al.Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass.N Engl J Med. 1995; 332: 549-555Crossref PubMed Scopus (608) Google Scholar, 3Bellinger D.C. Wypij D. Kuban K.C. 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: 526-532Crossref PubMed Scopus (470) Google Scholar, 4Bellinger D.C. Wypij D. duDuplessis A.J. et al.Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries the Boston Circulatory Arrest Trial.J Thorac Cardiovasc Surg. 2003; 126: 1385-1396Abstract Full Text Full Text PDF PubMed Scopus (543) Google Scholar, 5Wypij D. Newburger J.W. Rappaport L.A. et al.The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment the Boston Circulatory Arrest Trial.J Thorac Cardiovasc Surg. 2003; 126: 1397-1403Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar]. In the current era, however, alternatives to DHCA exist, giving surgeons the option in essentially all cases to either use or avoid DHCA. At this time, it seems relevant to review the real and theoretical risks related to the use of DHCA so that practicing pediatric heart surgeons can take advantage of the most recent knowledge regarding DHCA when making decisions relating to the management of extracorporeal circulation in the operating room.Pharmacologic and surgical strategies have evolved to minimize ischemic brain injury after DHCA; nevertheless, although experimental data are abundant, controversy still exists regarding optimal protective strategies. Several contemporary issues are contemplated, including the type of blood gas management to be undertaken during cooling, how long to cool and to what temperature, the “safe” duration of DHCA, continuous regional brain perfusion (CRBP), and the use of intermittent cerebral brain perfusion during DHCA.The purpose of this review is to summarize the experimental and clinical data available in the field of neonatal brain protection during DHCA. We will outline the pathophysiology of neonatal hypoxic brain injury associated with cardiopulmonary bypass and DHCA and will discuss the issue of selective vulnerability of the neonatal brain compared with the adult brain. Current techniques and limitations in neonatal brain protection will be described; additionally, we will discuss alternatives to DHCA. We will try to formulate, based on the available data, guidelines that might be helpful.To that extent, an extensive literature search was conducted through “Pub-Med” using several main key word combinations, including circulatory arrest, cardiopulmonary bypass, neonate, brain injury, neurologic damage, hypothermia, hemodilution, alpha stat, pH stat, and more. The search was conducted as far back as 1965 and as recently as May 2004.Pathophysiology of Neonatal Brain InjuryMechanisms of Cell DeathSeveral cellular and molecular mechanisms are responsible for the pathogenesis of neonatal hypoxic brain injury [6Johnston M.V. Trescher W.H. Ishida A. Nakajima W. Neurobiology of hypoxic-ischemic injury in the developing brain.Pediatr Res. 2001; 49: 735-741Crossref PubMed Scopus (383) Google Scholar]. Most of the available data originate from normothermic brain ischemia models. Neuronal cell death occurs by two distinct mechanisms, apoptosis and necrosis, that evolve over a period of hours to days. Prolonged ischemic injury leads to cell necrosis caused by adenosine triphosphate (ATP) depletion, and is characterized histologically by pyknotic nuclei, swollen eosinophilic cytoplasm, and the presence of an inflammatory reaction secondary to injury. Adenosine triphosphate depletion causes a failure of the Na+/K+ pump, leading to a massive osmotic diffusion of Na+, Cl-, and water into the cell, resulting in cellular swelling [7Murdoch J. Hall R. Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury.Can J Anaesth. 1990; 37: 663-671Crossref PubMed Scopus (40) Google Scholar]. The high intracellular Na+ concentration causes depolarization of the cell membrane, opening the voltage-sensitive Ca+2 channels, and a massive accumulation of Ca+2 ensues. Calcium ions activate intracellular proteases and lipases, which disrupt the cellular membrane and intracellular organelles. In summary, cellular necrosis is due to failure of the energy mechanisms that maintain cellular integrity.The second mechanism of cell death is by apoptosis, or programmed cell death, where cell death occurs despite adequate cellular energetics. Apoptosis is due to activation of specific genes, receptors, and enzymes that break down the cell in a programmed manner [8Thompson C.B. Apoptosis in the pathogenesis and treatment of disease.Science. 1995; 267: 1456-1462Crossref PubMed Scopus (6172) Google Scholar]; and it is characterized by nuclear karyorrhexis, margination of chromatin in the nucleus, but with minimal cytoplasmic and inflammatory changes. Apoptosis is mediated by a series of proteins that are sequentially activated and have a final common pathway leading to the generation of a family of cysteine proteases called caspases. The principal cysteine proteases involved in apoptosis are caspase 3 and caspase 8 [9Thornberry N.A. Lazebnik Y. Caspases enemies within.Science. 1998; 281: 1312-1316Crossref PubMed Scopus (6133) Google Scholar]. Caspase 3 can be activated by two principal pathways. The extrinsic pathway is initiated by the classic inflammatory response: soluble factors such as Fas and tumor necrosis factor alpha (TNF-α) bind to cell surface receptors and activate caspase 8, which in turn activates caspase 3. Intrinsic activation of caspase 3 is initiated by the release of cytochrome c from nonlethally damaged mitochondria.Apoptosis plays a crucial role in neuronal cell death after DHCA. Ditsworth and colleagues [10Ditsworth D. Priestley M.A. Loepke A.W. et al.Apoptotic neuronal death following deep hypothermic circulatory arrest in piglets.Anesthesiology. 2003; 98: 1119-1127Crossref PubMed Scopus (49) Google Scholar] demonstrated in a piglet model of DHCA that the apoptotic process starts within a few hours after reperfusion and continues for several days. In this study, piglets were subject to 90 minutes of DHCA at 19°C. After reperfusion and disconnection from cardiopulmonary bypass (CPB), the animals were sacrificed at several time points ranging from 4 hours to 1 week. Damaged neurons were observed as early as 8 hours after reperfusion and as long as 72 hours later. Cortical ATP levels were unchanged from control animals that underwent surgical preparation and were then sacrificed without being subjected to cardiopulmonary bypass or DHCA. In addition, caspase 3 and 8 concentration and activities were significantly higher in the DHCA group, as were cytosolic cytochrome c and Fas, which were significantly elevated 1 and 4 hours after DHCA [10Ditsworth D. Priestley M.A. Loepke A.W. et al.Apoptotic neuronal death following deep hypothermic circulatory arrest in piglets.Anesthesiology. 2003; 98: 1119-1127Crossref PubMed Scopus (49) Google Scholar].Ischemia and hypoxia have also been linked to excessive neuronal stimulation and hyperactivity, initiating a cascade of cellular events leading to neuronal cell death [11Choi D.W. Rothman S.M. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death.Annu Rev Neurosci. 1990; 13: 171-182Crossref PubMed Scopus (2021) Google Scholar, 12Olney J.W. Ho O.L. Rhee V. DeGubareff T. Neurotoxic effects of glutamate.N Engl J Med. 1973; 289 ([Letter]): 1374-1375Crossref PubMed Scopus (48) Google Scholar]. Excitotoxicity is a term applied to the death of cells caused by overstimulation of excitatory amino acids, mainly glutamate, and is believed to be a fundamental process involved in postischemic neuronal cell damage [6Johnston M.V. Trescher W.H. Ishida A. Nakajima W. Neurobiology of hypoxic-ischemic injury in the developing brain.Pediatr Res. 2001; 49: 735-741Crossref PubMed Scopus (383) Google Scholar, 13Baumgartner W.A. Walinsky P.L. Salazar J.D. et al.Assessing the impact of cerebral injury after cardiac surgery will determining the mechanism reduce this injury?.Ann Thorac Surg. 1999; 67: 1871-1874Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar]. Compromised synaptic reuptake of excitatory amino acids and membrane depolarization associated with ischemia cause a lethal flood of Ca+2 and Na+ into the neuron [6Johnston M.V. Trescher W.H. Ishida A. Nakajima W. Neurobiology of hypoxic-ischemic injury in the developing brain.Pediatr Res. 2001; 49: 735-741Crossref PubMed Scopus (383) Google Scholar, 11Choi D.W. Rothman S.M. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death.Annu Rev Neurosci. 1990; 13: 171-182Crossref PubMed Scopus (2021) Google Scholar]. High calcium concentrations activate nitric oxide synthetase (NOS), which leads to the production of nitric oxide (NO), a neuromodulator that in excess is thought to cause cell death [13Baumgartner W.A. Walinsky P.L. Salazar J.D. et al.Assessing the impact of cerebral injury after cardiac surgery will determining the mechanism reduce this injury?.Ann Thorac Surg. 1999; 67: 1871-1874Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar].The role of excitatory amino acids and NOS in the pathogenesis of ischemic brain injury after DHCA has been studied in a circulatory arrest model of mature dogs (7 to 12 months old) [14Redmond J.M. Gillinov A.M. Zehr K.J. et al.Glutamate excitotoxicity a mechanism of neurologic injury associated with hypothermic circulatory arrest.J Thorac Cardiovasc Surg. 1994; 107: 776-787PubMed Google Scholar, 15Tseng E.E. Brock M.V. Lange M.S. et al.Neuronal nitric oxide synthase inhibition reduces neuronal apoptosis after hypothermic circulatory arrest.Ann Thorac Surg. 1997; 64: 1639-1647Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar, 16Tseng E.E. Brock M.V. Kwon C.C. et al.Increased intracerebral excitatory amino acids and nitric oxide after hypothermic circulatory arrest.Ann Thorac Surg. 1999; 67: 371-376Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar]. Brain regions vulnerable to injury during prolonged circulatory arrest were found to have the highest density of glutamate receptors [14Redmond J.M. Gillinov A.M. Zehr K.J. et al.Glutamate excitotoxicity a mechanism of neurologic injury associated with hypothermic circulatory arrest.J Thorac Cardiovasc Surg. 1994; 107: 776-787PubMed Google Scholar]. Using intracerebral microdialysys techniques, Tseng and colleagues [17Tseng E.E. Brock M.V. Lange M.S. et al.Nitric oxide mediates neurologic injury after hypothermic circulatory arrest.Ann Thorac Surg. 1999; 67: 65-71Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar] demonstrated that DHCA increases intracerebral glutamate and aspartate concentrations along with the concentration of the coagonist glycine. Citrulline, which is produced in stoichiometric equivalent amounts with NO, was used as a marker of NO production, and was found to be elevated in parallel to the elevated concentrations of glutamate and aspartate [17Tseng E.E. Brock M.V. Lange M.S. et al.Nitric oxide mediates neurologic injury after hypothermic circulatory arrest.Ann Thorac Surg. 1999; 67: 65-71Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar]. The use of N-methyl-D-aspartate (NMDA) receptor blocker MK-801 significantly reduced citrulline production and apoptosis [14Redmond J.M. Gillinov A.M. Zehr K.J. et al.Glutamate excitotoxicity a mechanism of neurologic injury associated with hypothermic circulatory arrest.J Thorac Cardiovasc Surg. 1994; 107: 776-787PubMed Google Scholar, 18Tseng E. Brock M. Lange M.S. et al.NMDA receptor antagonist MK-801 reduces neuronal apoptosis in a canine model of hypothermic circulatory arrest.Surg Forum. 1996; 47: 266-269Google Scholar]; and the use of the neuronal nitric oxide inhibitor (7-nitroindsazole) in a canine model of DHCA significantly inhibited neuronal apoptosis as seen on hematoxylin-eosin staining, TUNEL (TdT-dNTP terminal nick-end labeling), and electron microscopy [15Tseng E.E. Brock M.V. Lange M.S. et al.Neuronal nitric oxide synthase inhibition reduces neuronal apoptosis after hypothermic circulatory arrest.Ann Thorac Surg. 1997; 64: 1639-1647Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar].Selective Vulnerability of the Developing BrainDeep hypothermic circulatory arrest inflicts a global and diffuse ischemic insult to the brain; nevertheless, damage is most likely to occur in select groups of structures in the immature brain [19Volpe J.J. Brain injury in the premature infant Neuropathology, clinical aspects, pathogenesis, and prevention.Clin Perinatol. 1997; 24: 567-587PubMed Google Scholar, 20Rivkin M.J. Hypoxic-ischemic brain injury in the term newborn Neuropathology, clinical aspects, and neuroimaging.Clin Perinatol. 1997; 24: 607-625PubMed Google Scholar]. Clinically, in adults, generalized Jacksonian type seizures follow severe hypoxic ischemic insults, whereas in neonates focal seizures are more common. Among infants aged 6 to 12 months, choreoathetosis can be a manifestation of ischemic neurologic postoperative insult, usually secondary to basal ganglia damage [21Jonas R.A. Neurological protection during cardiopulmonary bypass/deep hypothermia.Pediatr Cardiol. 1998; 19: 321-330Crossref PubMed Scopus (42) Google Scholar].The topography of selective neuronal cell death associated with DHCA has been shown in an adult canine experimental model of DHCA. It closely corresponded with the distribution of excitatory amino acid receptors in the pyramidal cells of the CA-1 region of the hippocampus, the molecular layer of the dentate nucleus the entorhinal cortex, and the molecular layer of the cerebellum [14Redmond J.M. Gillinov A.M. Zehr K.J. et al.Glutamate excitotoxicity a mechanism of neurologic injury associated with hypothermic circulatory arrest.J Thorac Cardiovasc Surg. 1994; 107: 776-787PubMed Google Scholar, 22Redmond J.M. Gillinov A.M. Blue M.E. et al.The monosialoganglioside, GM1, reduces neurologic injury associated with hypothermic circulatory arrest.Surgery. 1993; 114: 324-333PubMed Google Scholar]. Blocking these receptors with the specific glutamate NMDA receptor antagonist MK-801 improved the functional recovery of dogs subjected to 120 minutes of DHCA at 18°C and limited selective neuronal necrosis in the CA-1 region of the hippocampus, neocortex, basal ganglia, and cerebellum. Receptor autoradiography revealed significantly better preservation of NMDA glutamate receptor subtypes in the MK-801 treated animals [14Redmond J.M. Gillinov A.M. Zehr K.J. et al.Glutamate excitotoxicity a mechanism of neurologic injury associated with hypothermic circulatory arrest.J Thorac Cardiovasc Surg. 1994; 107: 776-787PubMed Google Scholar]. Selective vulnerability of neuronal populations in neonatal piglets after DHCA has been demonstrated to mainly affect the neocortex and hipoccampus [23Kurth C.D. Priestley M. Golden J. McCann J. Raghupathi R. Regional patterns of neuronal death after deep hypothermic circulatory arrest in newborn pigs.J Thorac Cardiovasc Surg. 1999; 118: 1068-1077Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar].Functional imaging evidence also indicates that normothermic hypoxic ischemic injury is linked to functionally hypermetabolic areas of the brain. Positron emission scans show relatively high metabolic rates of glucose utilization in the basal ganglia, brain stem, and sensory cortex of newborn babies, with much lower rates elsewhere [24Chugani H.T. Metabolic imaging a window at brain development and plasticity.Neuroscientist. 1999; 5: 29-40Crossref Scopus (46) Google Scholar]. Blennow and colleagues [25Blennow M. Ingvar M. Lagercrantz H. et al.Early [18F]FDG positron emission tomography in infants with hypoxic-ischaemic encephalopathy shows hypermetabolism during the postasphyctic period.Acta Paediatr. 1995; 84: 1289-1295Crossref PubMed Scopus (56) Google Scholar] evaluated brain glucose metabolism in infants with normothermic hypoxic ischemic encephalopathy, and found focal elevations in selective metabolism of glucose in the basal ganglia and cerebral cortex of 5 infants who later had severe neurologic deficits. The 1 infant who had normal cerebral glucose metabolism was neurologically normal at follow up [25Blennow M. Ingvar M. Lagercrantz H. et al.Early [18F]FDG positron emission tomography in infants with hypoxic-ischaemic encephalopathy shows hypermetabolism during the postasphyctic period.Acta Paediatr. 1995; 84: 1289-1295Crossref PubMed Scopus (56) Google Scholar].Cerebral EnergeticsMetabolic and cellular energy changes have been found to be associated with low-flow cardiopulmonary bypass and DHCA [26Kramer R.S. Sanders A.P. Lesage A.M. Woodhall B. Sealy W.C. The effect profound hypothermia on preservation of cerebral ATP content during circulatory arrest.J Thorac Cardiovasc Surg. 1968; 56: 699-709PubMed Google Scholar]. Kramer and colleagues [26Kramer R.S. Sanders A.P. Lesage A.M. Woodhall B. Sealy W.C. The effect profound hypothermia on preservation of cerebral ATP content during circulatory arrest.J Thorac Cardiovasc Surg. 1968; 56: 699-709PubMed Google Scholar] evaluated cerebral ATP changes during normothermic and hypothermic circulatory arrest in mature mongrel dogs. In the normothermic circulatory arrest group, ATP levels were found to decrease to half their baseline values after 3.8 minutes (calculated half-life) of circulatory arrest. Electroencephalographioc silence occurred 20 seconds after the initiation of normothermic circulatory arrest, corresponding to a 10% reduction of ATP from baseline levels. The ATP recovery rates inversely correlated with the duration of cerebral ischemia. Deep hypothermic circulatory arrest performed at esophageal temperatures of 7.8 ± 2.5°C and at average cortical temperatures of 13 ± 2.7°C demonstrated a calculated half-life of 13.3 minutes compared with 3.8 minutes observed under normothermic conditions. The disappearance of cortical electrical activity was noted at 16.6 ± 3.5°C during cooling, coinciding with a reduction of less than 10% of control ATP concentrations.In vivo phosphorus-31 nuclear magnetic resonance spectroscopy was used to assess the metabolic state of the brain during circulatory arrest by measuring the concentrations of high-energy phosphate compounds and intracellular pH [27Swain J.A. McDonald Jr, T.J. Robbins R.C. Balaban R.S. Relationship of cerebral and myocardial intracellular pH to blood pH during hypothermia.Am J Physiol. 1991; 260: H1640-H1644PubMed Google Scholar]. Sheep were cooled to 15°C and were subject to either circulatory arrest or low-flow CPB. Both circulatory arrest and low-flow of 5 mL · kg-1 · min-1 resulted in severe intracellular acidosis and depletion of high energy phosphates However, flows of 10 mL · kg-1 · min-1 maintained both brain high-energy phosphate concentrations and intracellular pH.Human Clinical StudiesNewburger and colleagues [1Newburger J.W. Jonas R.A. Wernovsky G. et al.A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery.N Engl J Med. 1993; 329: 1057-1064Crossref PubMed Scopus (592) Google Scholar] prospectively evaluated 171 neonates with D-transposition of the great arteries who underwent the arterial switch operation between 1988 and 1992 and were randomly assigned either to DHCA or low-flow CPB. In the immediate postoperative period, the use of DHCA was associated with a higher risk of clinical seizures (12%), seizures detected by electroencephalography (EEG [26%]), and with a greater release of brain isoenzyme creatine kinase. Clinical seizures were associated with a longer period of circulatory arrest and with arrest times longer than 35 minutes [1Newburger J.W. Jonas R.A. Wernovsky G. et al.A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery.N Engl J Med. 1993; 329: 1057-1064Crossref PubMed Scopus (592) Google Scholar]. Nevertheless, at the time of hospital discharge, the groups were similar in their overall incidence of neurologic abnormalities. At a 1-year follow-up, infants who underwent surgical repair with DHCA had a 6.5 point deficit on the Bayley Scale of Infant Development (p = 0.01), and a higher percentage of patients had scores that were lower than 80 (27% versus 12%, p = 0.02). A negative correlation between the duration of the circulatory arrest and developmental scores was noted. In addition, the occurrence of perioperative seizures was associated with a lower Psychomotor Developmental Index score and with a significantly higher risk of possible, or definite, abnormalities on magnetic resonance imaging (MRI) [2Bellinger D.C. Jonas R.A. Rappaport L.A. et al.Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass.N Engl J Med. 1995; 332: 549-555Crossref PubMed Scopus (608) Google Scholar]. At 4 years of age, neither IQ scores nor overall neurologic status differed between children repaired with DHCA or low-flow bypass. However, the DHCA group had lower motor scores (gross motor, p = 001; fine motor, p = 0.03) and greater speech abnormalities (oromotor apraxia, 33% versus 18%, p = 0.03) [3Bellinger D.C. Wypij D. Kuban K.C. 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: 526-532Crossref PubMed Scopus (470) Google Scholar]. Again, the occurrence of perioperative seizures was associated with lower IQ scores (mean deficit 12.6, p = 0.01) and increased risk of neurologic abnormalities (odds ratio 8.4, p = 0.05). Treatment groups did not differ in primary endpoints of intelligence, reading, and mathematics, or in many of the neuropsychological outcomes. However, the DHCA group performed worse on tests of fine motor and visual-spatial skills [4Bellinger D.C. Wypij D. duDuplessis A.J. et al.Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries the Boston Circulatory Arrest Trial.J Thorac Cardiovasc Surg. 2003; 126: 1385-1396Abstract Full Text Full Text PDF PubMed Scopus (543) Google Scholar].Neonatal Brain ProtectionTo protect the neonatal brain from injury due to circulatory arrest and ischemia, several anesthetic and surgical strategies have been developed. These include the use of hypothermia, pH stat blood gas management, pharmacologic agents (such as volatile anesthetics, steroids, and aprotinin), and the development of techniques aimed at minimizing and even avoiding circulatory arrest, such as the use of low-flow cardiopulmonary bypass, intermittent cerebral perfusion, and continuous regional brain perfusion. In the following section, each of these strategies is briefly reviewed.Hypothermia and HemodilutionThe brain utilizes up to 20% of total body oxygen consumption, with 40% of its energy consumption used in the preservation of cellular integrity and 60% in the transmission of nerve impulses [28Michenfelder J.D. Theye R.A. Cerebral protection by thiopental during hypoxia.Anesthesiology. 1973; 39: 510-517Crossref PubMed Scopus (152) Google Scholar]. Electrocerebral silence and the disappearance of the somatosensory evoked response occurs at approximately nasopharyngeal temperature of 17°C [29Stecker M.M. Cheung A.T. Pochettino A. et al.Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials.Ann Thorac Surg. 2001; 71: 14-21Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar, 30Ghariani S. Liard L. Spaey J. et al.Retrospective study of somatosensory evoked potential monitoring in deep hypothermic circulatory arrest.Ann Thorac Surg. 1999; 67: 1915-1921Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. Thus, theoretically, lowering brain temperature would reduce much of its metabolic demands. The rate of change of a reaction for every 10°C change in temperature is referred to as Q10. Kern and colleagues [31Kern F.H. Ungerleider R.M. Reves J.G. et al.Effect of altering pump flow rate on cerebral blood flow and metabolism in infants and children.Ann Thorac Surg. 1993; 56: 1366-1372Abstract Full Text PDF PubMed Scopus (50) Google Scholar] evaluated the rate by which cerebral O2 metabolism decreases in relation to pump flow and metabolism. They noted that, as temperatures were lowered, the cerebral oxygen extraction rate and the estimated minimal pump flow rates decreased logarithmically. The Q10 was higher for infants and children (Q10 = 3.65) than for adults (Q10 = 2.6), implying that changes in temperature have greater impact in cerebral oxygen consumption in pediatric subjects than in adults. This finding reflects the greater metabolic suppression by hypothermia in the pediatric population [32Greeley W.J. Kern F.H. Ungerleider R.M. et al.The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children.J Thorac Cardiovasc Surg. 1991; 101: 783-794PubMed Google Scholar].What temperature provides optimal brain protection during DHCA? Early experience with deep hypothermia suggested that using extremely low temperatures resulted in a dramatic increase in neurologic and pulmonary injury [33Brunberg J.A. Doty D.B. Reilly E.L. Choreoathetosis in infants following cardiac surgery with deep hypothermia and circulatory arrest.J Pediatr. 1974; 84: 232-235Abstract Full Text PDF PubMed Scopus (62) Google Scholar, 34DeLeon S. Ilbawi M. Arcilla R. et al.Choreoathetosis after deep hypothermia without circulatory arrest.Ann Thorac Surg. 1990; 50: 714-719Abstract Full Text PDF PubMed Scopus (71) Google Scholar]. DeLeon and colleagues [34DeLeon S. Ilbawi M. Arcilla R. et al.Choreoathetosis after deep hypothermia without circulatory arrest.Ann Thorac Surg. 1990; 50: 714-719Abstract Full Text PDF PubMed Scopus (71) Google Scholar] reported that choreoathetosis developed in 8 of 758 patients operated on using cardiopulmonary bypass and hypothermia, the incidence being significantly higher in the group of patients for whom deep hypothemia (rectal temperature lower than 25°C) was used (8 of 463 versus 0 of 295, p = 0.02) and for whom the cooling time (the time to cool the patient to a target temperature) was longer than 1 hour (7 of 243 versus 1 of 220, p = 0.05) [34DeLeon S. Ilbawi M. Arcilla R. et al.Choreoathetosis after deep hypothermia without circulatory arrest.Ann Thorac Surg. 1990; 50: 714-719Abstract Full Text PDF PubMed Scopus (71) Google Scholar]. On the other hand, recent experimental publications have demonstrated that pr" @default.
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• W1986306295 date "2005-11-01" @default.
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• W1986306295 title "Neonatal Brain Protection and Deep Hypothermic Circulatory Arrest: Pathophysiology of Ischemic Neuronal Injury and Protective Strategies" @default.
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