Cerebral Oxygenation during Pediatric Cardiac Surgery Using Deep Hypothermic Circulatory Arrest

Background: Deep hypothermic circulatory arrest is a widely used technique in pediatric cardiac surgery that carries a risk of neurologic injury. Previous work in neonates identified distinct changes in cerebral oxygenation during surgery. This study sought to determine whether the intraoperative changes in cerebral oxygenation vary between neonates, infants, and children and whether the oxygenation changes are associated with postoperative cerebral dysfunction.

Methods: The study included eight neonates, ten infants, and eight children without preexisting neurologic disease. Cerebrovascular hemoglobin oxygen saturation (ScO2), an index of brain oxygenation, was monitored intraoperatively by near-infrared spectroscopy. Body temperature was reduced to 15 degrees Celsius during cardiopulmonary bypass (CPB) before commencing circulatory arrest. Postoperative neurologic status was judged as normal or abnormal (seizures, stroke, coma).

Results: Relative to preoperative levels, the age groups experienced similar changes in ScO2 during surgery: Sco sub 2 increased 30 plus/minus 4% during deep hypothermic CPB, it decreased 62 plus/minus 5% by the end of arrest, and it increased 20 plus/minus 5% during CPB recirculation (all P < 0.001); after rewarming and removal of CPB, ScO2 returned to preoperative levels. During arrest, the half-life of ScO2 was 9 plus/minus 1 min in neonates, 6 plus/minus 1 min in infants, and 4 plus/minus 1 min in children (P < 0.001). Postoperative neurologic status was abnormal in three (12%) patients. The ScO2 increase during deep hypothermic CPB was less in these patients than in the remaining study population (3 plus/minus 2% versus 33 plus/minus 4%, P < 0.00l). There were no other significant ScO2 differences between outcome groups.     

Hypothermic Asanguineous Circulatory Arrest in Adult Dogs

A new technique for the institution of hypothermic asanguineous circulatory arrest (HACA) is described and evaluated. It employs rapid cooling and hemodilution at high flow rates. Survival and protection of neurologic and other organ function were obtained using asanguineous circulatory arrest, and the method appears to be an improvement over circulatory arrest using conventional methods for cooling. The total duration of extracorporeal circulation is much shorter than with currently used methods of circulatory arrest. Applications of this technique in general and transplantation surgery as well as cardiac surgery are discussed.     

腋动脉侧接人工血管插管法在深低温停循环手术中的应用

目的介绍腋动脉侧接人工血管插管法在深低温停循环手术中的应用,总结其经验。方法2006年1月至2008年12月,我们在36例A型主动脉夹层的患者中应用腋动脉侧接人工血管插管法建立体外循环中的动脉灌注;将右侧腋动脉游离,全身肝素化,前后阻断腋动脉,于腋动脉前壁作一长约8～10mm切口,用一直径8～10mm、长约6～8cm的人工血管与腋动脉行端侧吻合,侧接人工血管与普通升主动脉插管连接。结果施行腋动脉侧接人工血管顺利,成功率为100%,体外循环及选择性脑灌注满意。无腋动脉插管的相关并发症发生,除2例苏醒延迟外,其余均无神经系统并发症。手术死亡3例,死亡原因与腋动脉侧接人工血管插管无关。结论腋动脉侧接人工血管插管法作为心脏大血管深低温停循环手术中建立体外循环的动脉灌注及选择性脑灌注,其方法简单、疗效可靠、无插管相关并发症,值得临床应用。     

Cerebral Consequences of Hypothermic Circulatory Arrest in Adults

Despite widespread use of hypothermic circulatory arrest (HCA) in aneurysm surgery and for repair of congenital heart defects, there is continued concern about possible adverse cerebral sequelae. The search for ways to improve implementation of HCA has inspired retrospective clinical studies to try to identify risk factors for cerebral injury, and clinical and laboratory investigations to explore the physiology of HCA. At present, risk factors associated with less favorable cerebral outcome after HCA include: prolonged duration of HCA (usually greater than 60 min); advanced patient age; rapid cooling (less than 20 min); hyperglycemia either before HCA or during reperfusion; preoperative cyanosis or lack of adequate hemodilution; evidence of increased oxygen extraction before HCA or during reperfusion; and delayed reappearance of electroencephalogram (EEG) or marked EEG abnormality. Strategies advocated to increase safety of HCA include: pretreatment with barbiturates and steroids; use of alpha-stat pH regulation during cooling and rewarming; intraoperative monitoring of EEG; slow and adequate cooling, including packing of the head in ice; monitoring of jugular venous oxygen content; hemodilution; and avoidance of hyperglycemia. Current investigation focuses on delineating the relationship of cerebral blood flow (CBF) to cerebral oxygen consumption and glucose metabolism during cooling, HCA, rewarming, and later recovery, and identifying changes in acute intraoperative parameters, including the presence of intracerebral enzymes in cerebral spinal fluid, with cerebral outcome as assessed by neurological evaluation, quantitative EEG, and postmortem histology. Clinically, intraoperative monitoring of EEG and measurement of CBF by tracer washout or Doppler flows are contributing to better understanding of the physiology of HCA, and in the laboratory, nuclear magnetic resonance (NMR) spectroscopy has provided valuable insights into the kinetics of intracerebral energy metabolism. Promising strategies for the future include investigation of other pharmacological agents to increase cerebral protection, and use of "cerebroplegia" or intermittent perfusion between intervals of HCA to improve cerebral tolerance for longer durations of HCA.     

Immediate-early Gene Expression in Ovine Brain after Cardiopulmonary Bypass and Hypothermic Circulatory Arrest

Background: Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are associated with neurological injury. Altered immediate-early gene expression occurs rapidly in the brain in response to ischemia, hypoxia, and severe metabolic stress, which results in long-term changes in the molecular phenotype of neurons. This study determined the effects of CPB and HCA on the expression of the immediate-early gene c-fos.

Methods: Neonatal lambs were subjected to 2 h of CPB at 38 degrees Celsius (n = 4) or 60 min (n = 6), 90 min (n = 7), and 120 min (n = 6) of HCA at 15 degrees Celsius. One hour after terminating CPB at 38 degrees Celsius, the brains were analyzed for FOS-encoding mRNA and FOS-like immunoreactivity in the hippocampal formation. Other animals (n = 15), subjected to the same CPB and HCA protocol, were allowed to survive 3-5 days before their brains were examined for dead neurons.

Results: Minimal c-fos mRNA and FOS proteins were observed in neurons of animals subjected to normothermic bypass and of those that served as controls. Non-neuronal FOS proteins were observed in the choroid plexus, ependyma, and blood vessels at all times, including normothermic CPB, but not in the control animals without CPB. The magnitude of c-fos mRNA expression in hippocampal neurons increased directly with the duration of HCA. In contrast, expression of FOS proteins peaked after 90 min of HCA and declined significantly thereafter. Dead neurons were seen in surviving animals after 2 h of HCA only.     

Deep Brain Hyperthermia While Rewarming from Hypothermic Circulatory Arrest

Abstract   Background: Neurologic injury is a feared and serious long-term complication of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Postoperative hyperthermia was found to enhance postischemic neurologic injury. The use of core temperature as the reference point through CPB assumes parallel changes in brain temperature. We tested the hypothesis that regional and deep brain temperature (DBT) differ during cooling, DHCA, and rewarming. Methods: Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature (RT) of 18 °C, 30 minutes of DHCA were initiated, and subsequently the piglets were rewarmed to RT of 36.5 °C and weaned from CPB. Temperature probes were inserted into the DBT targeting the caudate and thalamic nuclei, their position confirmed by pathology. Superficial brain temperature was measured by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and tympanic (TT) temperatures were recorded. Results: During cooling the deep brain cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT accurately. During rewarming DBT was significantly higher than RT and TT. By the end of rewarming the difference between the deep brain and the RT reached statistical significance (30 minutes: 35.1 ± 0.7 vs. 32.3 ± 0.7 p < 0.05, respectively, 40 minutes: 37.5 ± 0.3 vs. 34.7 ± 0.8 p < 0.05, respectively). Conclusion: Deep brain hyperthermia routinely occurs during the last stages of rewarming following DHCA. DBT is accurately reflected by NPT and is directly correlated with inflow temperature. Therefore, during rewarming inflow temperatures should not exceed 36 °C and NPT should be closely monitored.     

Differential Immediate-early Gene Expression in Ovine Brain after Cardiopulmonary Bypass and Hypothermic Circulatory Arrest

Background: This study determined the induction profiles of immediate-early genes in the ovine brain after cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA), and the effects of the noncompetitive N-methyl-D-aspartate antagonist, aptiganel, on immediate-early gene expression, neuronal necrosis, and functional outcome.

Methods: Cannulas were inserted into isoflurane-anesthetized neonatal lambs undergoing CPB. One group received 2.5 mg/kg intravenous aptiganel. Animals underwent 90 or 120 min of HCA at 16 [degree sign]C, were rewarmed to 38 [degree sign]C, and were weaned from CPB. One hour after CPB was discontinued, brain perfusion was fixed and removed for immunohistochemical analysis in one half of the animals. The other half survived 2 or 3 days before their brains were evaluated for neuronal degeneration. Data were analyzed using analysis of variance; P < 0.05 was considered significant.

Results: Cardiopulmonary bypass and HCA differentially induced c-Jun and Fos proteins in the hippocampal formation, with c-Jun expression increasing with the duration of HCA, whereas Fos protein expressions were greatest after 90 min of HCA. The c-Jun protein was expressed in all neurons except the dentate gyrus. The Fos proteins were expressed in all neurons, including the dentate gyrus. Neuronal necrosis was observed in CA1 (73%) and CA3 (29%) neurons but not in the dentate gyrus after 120 min of HCA. Aptiganel completely inhibited c-Jun expression (P < 0.001) but not Fos, improved functional outcome, and attenuated neuronal necrosis (P < 0.05).