Xenon impairs neurocognitive and histologic outcome after cardiopulmonary bypass combined with cerebral air embolism in rats

BACKGROUND: The neuroprotective properties of xenon may improve cerebral outcome after cardiac surgery using cardiopulmonary bypass (CPB). However, its disposition to expand gaseous bubbles that during CPB present as cerebral air emboli (CAE) could abolish any beneficial effect or even worsen cerebral outcome. Therefore, the authors studied the impact of xenon on neurologic, cognitive, and histologic outcome after CPB combined with CAE in rats. METHODS: With institutional review board approval, 40 rats were assigned to four groups (n = 10). In two CPB-CAE groups, rats were subjected to 90 min of normothermic CPB with 10 repetitively administered CAEs (0.3 microl/bolus). Rats in two sham groups were not exposed to CPB and CAE. Groups were further subdivided into xenon (56%; 20 min before, during, and 30 min after CPB) and nitrogen groups. Neurologic and cognitive function was tested until postoperative day 14, when cerebral infarct volumes were determined. RESULTS: Animals of the CPB-CAE groups showed transient deficits in gross neurologic function. Further, rats of the CPB-CAE-xenon group demonstrated impaired fine motor and cognitive performance persisting until postoperative day 14. Consistently, infarct volumes were larger in the CPB-CAE-xenon group compared with the CPB-CAE-nitrogen group (P = 0.03). CONCLUSIONS: This is the first demonstration in which the neurologic effects of CAE have been examined in a rat model of CPB. Xenon exposure aggravated the neurologic dysfunction that is produced by CAE during CPB; potential neuroprotective effects of xenon may have been masked by the effects of xenon on CAE.     

Cerebral injury during cardiopulmonary bypass: emboli impair memory

OBJECTIVES: Cognitive deficits occur in up to 80% of patients after cardiac surgery. We investigated the influence of cerebral perfusion and embolization during cardiopulmonary bypass on cognitive function and recovery. METHODS: Cerebrovascular reactivity was measured in 70 patients before coronary operations in which nonpulsatile bypass was used. Throughout the operations, middle cerebral artery flow velocity and embolization were recorded by transcranial Doppler and regional oxygen saturation was recorded by near-infrared spectroscopy. Cognitive function was measured by a computerized battery of tests before the operation and 1 week, 2 months, and 6 months after surgery. Elderly patients undergoing urologic surgery served as controls. RESULTS: Cerebrovascular reactivity was impaired preoperatively in 49 patients. Median (interquartile range) regional cerebral oxygen saturation fell during bypass by 10% (6%-15%), indicating increased oxygen extraction, whereas mean middle cerebral flow velocity increased significantly by a median of 6 cm/s (both P <.0001, Wilcoxon), suggesting increased arterial tone. More than 200 emboli were detected in 40 patients, mainly on aortic clamping and release, when bypass was initiated, and during defibrillation. Cognitive function deteriorated more in patients having cardiopulmonary bypass than in control patients having urologic operations but recovered in most tests by 2 months. Measures of cerebral perfusion (poor cerebrovascular reactivity, low arterial pressures, and flow velocity in the middle cerebral artery) predicted poor attention at 1 week (r = 0.3, P <.01, Spearman). Emboli were associated with memory loss (r = 0.3, P <.02, Spearman). CONCLUSIONS: Cognitive deficits were common after cardiopulmonary bypass. Occult cerebrovascular disease was more severe than expected and predisposed to attention difficulties, whereas emboli caused memory deficits. We believe this to be the first report of differing cognitive effects from emboli and hypoperfusion.     

Cerebral hyperthermia in children after cardiopulmonary bypass

BACKGROUND: Cerebral hyperthermia after hypothermic cardiopulmonary bypass has been poorly documented for adults and never in children. This study was designed to monitor brain temperature during and up to 6 h after cardiopulmonary bypass in infants and children. METHODS: Fifteen infants and children, between 3 months and 6 yr of age, were studied. A right retrograde jugular bulb catheter was used to measure the jugular venous bulb temperature (JVBT) during the procedure and the first 6 h in the critical care unit. The temperature of the blood from the bypass machine was measured at the aorta through the cannula using an indwelling temperature probe. All data were acquired every minute. RESULTS: The age of the patients ranged from 3 to 71 months (median, 15 months). The mean weight was 11.5 +/- 8.4 kg. The mean JVBT recorded at the end of cardiopulmonary bypass was 36.9 +/- 1.4 degrees C but reached 39.6 +/- 0.8 degrees C after six h (P < 0.01). The kinetics of brain rewarming was determined by the slope of the mean JVBT and corresponded to y +/- 0.006x + 37.21 (r2 = 0.97). The JVBT differed from the tympanic temperature after 200 min (P < 0.01) and the lower esophageal (P < 0.05) and rectal (P < 0.001) temperatures after 300 min. After 6 h, the tympanic, rectal, and lower esophageal temperatures were 37.8 +/- 0.9, 37.7 +/- 0.6, and 38.4 +/- 0.7 degrees C, respectively, whereas the JVBT was 39.6 +/- 0.8 degrees C (P < 0.001). However, the correlation coefficients between the JVBT and the tympanic, rectal, and esophageal temperatures were 0.98, 0. 85, and 0.97, respectively. No complications were recorded with placement of the jugular bulb catheter. CONCLUSIONS: Mean JVBT was significantly increased over the mean core temperature at all times from rewarming by cardiopulmonary bypass onward. Although the lower esophageal, rectal, and tympanic temperatures correlated well with JVBT, all three failed to reflect JVBT during recovery. This observation might help to elucidate factors involved in the functional and structural neurologic injury known to occur in pediatric patients.     

Cerebral microemboli during cardiopulmonary bypass: increased emboli during perfusionist interventions.

BACKGROUND: Microemboli to the cerebral circulation occur during cardiopulmonary bypass (CPB) and can contribute to postoperative neurologic dysfunction. Cerebral microemboli are known to occur during specific surgical interventions, but the source of a large proportion of emboli remains unexplained. We investigated whether interventions by the perfusionist could account for the appearance of cerebral microemboli. METHODS: Transcranial Doppler ultrasonography was used to continuously monitor the middle cerebral artery of 18 patients undergoing coronary artery bypass grafting. The CPB circuit consisted of a softshell venous reservoir, a hollow-fiber membrane oxygenator, and a 32-microm arterial filter. The mean embolic rate was calculated for three time periods: (1) during surgical interventions (aortic cannulation and decannulation, cross-clamp application and removal, CPB start and end, and start of cardiac ejection); (2) during perfusionist interventions (blood sampling and drug administration into the venous reservoir); and (3) during baseline (all other time periods during CPB). RESULTS: Microemboli were detected in all patients (mean +/- standard deviation, 207+/-142 per patient, median, 132). The number of emboli per minute was significantly (p < 0.001) higher during perfusionist interventions (6.9+/-4.5) than during surgical interventions (1.5+/-1.5) or during baseline (0.4+/-0.5). Drug administration resulted in a higher embolic rate than blood sampling. CONCLUSIONS: Interventions by the perfusionist account for a large proportion of previously unexplained cerebral microemboli during CPB. These emboli likely represent air bubbles that are not eliminated by the arterial line filter. Although further studies of additional types of CPB circuits are required, we believe that air in the venous reservoir should be avoided whenever possible to minimize the risk of neurologic injury.     

Cerebral emboli during cardiopulmonary bypass: effect of perfusionist interventions and aortic cannulas

Neuropsychological impairment is a very common complication of cardiopulmonary bypass (CPB). The principal cause of postoperative cognitive impairment is thought to be cerebral microemboli during CPB. We recently investigated the effects of perfusionist interventions and aortic cannulation techniques on cerebral emboli production during coronary bypass (CABG) surgery. Patients undergoing isolated CABG were monitored with continuous transcranial Doppler ultrasonography of the middle cerebral artery. Perfusionist interventions were defined as injections of drugs into the CPB circuit or acquisition of blood samples from the CPB circuit. Patients were randomized to receive either standard cannulation of the ascending aorta or cannulation of the distal aortic arch. Cerebral emboli were detected in all patients. The number of emboli per minute was markedly higher during perfusionist interventions than during other time periods. Patients with increased perfusionist interventions had worse neuropsychological outcomes. Cannulation of the distal aortic arch, with placement of the cannula tip beyond the cerebral vessels, resulted in significantly less cerebral emboli than cannulation of the ascending aorta. Perfusionist interventions are a common source of cerebral microemboli during CPB, and may contribute to postoperative neuropsychological impairment. Care should be taken to minimize the introduction of air into the bypass circuit during CPB. Provided it is performed safely, distal aortic arch cannulation is a useful technique for reducing cerebral emboli during cardiac surgery.     

Cerebral physiology in paediatric cardiopulmonary bypass

Purpose  To analyze studies of neurological injury after open-heart surgery in infants and children and to discuss the effects of cardiopulmonary bypass, hypothermia and deep hypothermic circulatory arrest on cerebral blood flow, cerebral metabolism and brain temperature. Source  Articles were obtained from the databases, Current Science and Medline, from 1966 to present. Search terms include cardiopulmonary bypass(CPB), hypothermia, cerebral blood flow(CBF), cerebral metabolism and brain temperature. Information and abstracts obtained from meetings on the topic of brain and cardiac surgery helped complete the collection of information. Principal findings  In adults the incidence of neurological morbidity is between 7 to 87% with stroke in about 2–5%, whereas the incidence of neurological morbidity increases to 30% in infants and children undergoing cardiopulmonary bypass. Besides the medical condition of the patient, postoperative cerebral dysfunction and neuronal ischaemia associated with cardiac surgery in infants and small children are a combination of intraoperative factors. Deep hypothermic circulatory arrest impairs CBF and cerebral metabolism even after termination of CPB. Inadequate and/or non-homogenous cooling of the brain before circulatory arrest, as well as excessive rewarming of the brain during reperfusion are also major contributory factors. Conclusion  Newer strategies, including the use of low-flow CPB, pulsatile CPB, pH-stat acid-base management and a cold reperfusion, are being explored to ensure better cerebral protection. Advances in monitoring technology and better understanding of the relationship of cerebral blood flow and metabolism during the different modalities of cardiopulmonary bypass management will help in the medical and anaesthetic development of strategies to improve neurological and developmental outcomes.

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Résumé Objectif  Examiner les études portant sur les atteintes neurologiques survenues après une chirurgie à cœur ouvert chez les bébés et les enfants et discuter des effets de la circulation extracorporelle, de l’hypothermie et de l’arrêt circulatoire sous hypothermie profonde sur le débit sanguin cérébral, sur le métabolisme cérébral et sur la température du cerveau. Sources documentaires  Des articles ont été choisis à partir de bases de données, Current Science et Medline, de 1966 à aujourd’hui. Les mots-clés utilisés étaient: circulation extracorporelle (CEC), hypothermie, débit sanguin cérébral (DSC), métabolisme cérébral et température du cerveau. Les informations et les résumés obtenus à la suite de séminaires sur le cerveau et la chirurgie cardiaque ont permis de compléter la cueillette de données. Données principales  Chez les adultes, l’incidence de morbidité neurologique avec accident vasculaire est de 7 à 87 % dans 2 à 5 % des cas tandis que l’incidence de morbidité neurologique augmente à 30 % chez les bébés et les enfants subissant une circulation extracorporelle. La condition médicale du patient mise à part, le dérèglement cérébral postopératoire et l’ischémie neuronale associés à la chirurgie cardiaque chez les enfants et les nouveau-nés sont une combinaison de facteurs peropératoires. L’arrêt circulatoire sous hypothermie profonde altère le DSC et le métabolisme cérébral même après la CEC. Un refroidissement du cerveau incomplet et/ou non homogène avant l’arrêt circulatoire, de même qu’un réchauffement excessif du cerveau pendant la reperfusion, constituent également des facteurs importants. Conclusion  Des stratégies nouvelles comprenant la CEC à faible débit, la CEC pulsatile, le traitement acidobasique par pH-stat et une reperfusion froide sont à l’étude pour assurer une meilleure protection cérébrale. Des progrès dans la technologie du monitorage et une meilleure connaissance de la relation entre le débit sanguin cérébral et le métabolisme cérébral pendant les différentes étapes de la circulation extracorporelle pourront favoriser l’élaboration de stratégies médicales et anesthésiques visant à diminuer les atteintes neurologiques et à améliorer le développement de l’enfant.

     

Incidence and outcome of gastrointestinal complications after cardiopulmonary bypass

Gastrointestinal complications (GI-complications) after CPB are rare, but are associated with high mortality and hospital cost. This retrospective analysis investigates the incidence, patient profile and post-operative course of GI-complications after CPB. The charts of 8869 adult patients, operated on CPB between 1995 and 2002, were reviewed. Patients with post-OP GI-complications were compared to a control group of 1057 consecutive patients operated on CPB between 05/2000 and 04/2001. The incidence of GI-complications was 0.79% with an overall mortality of 21.5% (vs. 3% in controls, P<0.05). Most frequent were upper GI-tract-bleeding (58%), followed by pancreatitis (11%) and cholecystitis (10%). GI-complications were diagnosed 9.2+/-5.9 days after surgery, with 58.5% after a primarily uneventful post-op course. Compared to control, patients with GI-complications showed no difference in pre-operative comorbidity and EuroSCORE. However, surgery of the thoracic aorta, prolonged CPB time, and necessity for re-thoracotomy was significantly more frequent in patients with GI-complications (P<0.05). GI-complications after CPB remain a rare, but dreaded complication associated with high mortality. Early diagnosis may require a high degree of clinical vigilance as the majority of GI-complications occurred after a primarily uneventful post-op course. Age, co-morbidity, and EuroSCORE were not different between patients with GI-complications and control.     

Desflurane improves neurologic outcome after low-flow cardiopulmonary bypass in newborn pigs

BACKGROUND: Despite improvements in neonatal heart surgery, neurologic complications continue to occur from low-flow cardiopulmonary bypass (LF-CPB) and deep hypothermic circulatory arrest (DHCA). Desflurane confers neuroprotection against ischemia at normothermia and for DHCA. This study compared neurologic outcome of a desflurane-based with a fentanyl-based anesthetic for LF-CPB. METHODS: Thirty piglets aged 1 week received either fentanyl-droperidol (F/D), desflurane 4.5% (Des4.5), or desflurane 9% (Des9) during surgical preparation and CPB. Arterial blood gases, glucose, heart rate, arterial pressure, brain temperature, and cerebral blood flow (laser Doppler flowmetry) were recorded. After CPB cooling (22 degrees C brain) using pH-stat strategy, LF-CPB was performed for 150 min followed by CPB rewarming, separation from CPB, and extubation. On postoperative day 2, functional and histologic outcomes were assessed. RESULTS: Cardiovascular variables were physiologically similar between groups before, during, and after LF-CPB. Cerebral blood flow during LF-CPB (13% of pre-CPB value) did not differ significantly between the groups. Functional disability was worse in F/D than in Des9 (P = 0.04) but not Des4.5 (P = 0.1). In neocortex, histopathologic damage was greater in F/D than in Des4.5 (P = 0.03) and Des9 (P = 0.009). In hippocampus, damage was worse in F/D than in Des9 (P = 0.01) but not Des4.5 (P = 0.08). The incidences of ventricular fibrillation during LF-CPB were 90, 60, and 10% for F/D, Des4.5 (P = 0.06), and Des9 (P = 0.0002), respectively. CONCLUSIONS: Desflurane improved neurologic outcome following LF-CPB compared with F/D in piglets, indicated by less functional disability and less histologic damage, especially with Des9. Desflurane may have produced cardiac protection, suggested by a lower incidence of ventricular fibrillation.     

Favorable outcome with bivalirudin anticoagulation during cardiopulmonary bypass

An 81-year-old man with previous syncopal episodes, progressive shortness of breath, pulmonary edema, severe calcific aortic stenosis, and a history of heparin-induced thrombocytopenia required aortic valve replacement. Bivalirudin, a thrombin-specific anticoagulant, was used in place of heparin. The patient received a 50 mg bivalirudin bolus followed by an infusion between 1.5 mg x kg(-1) x h(-1) and 1.75 mg x kg(-1) x h(-1). Adequate anticoagulation was readily obtained resulting in an uneventful cardiopulmonary bypass. Activated clotting time (ACT) values steadily declined after discontinuation of the bivalirudin infusion. Bivalirudin is a practical alternative to heparin during cardiac surgical procedures.     

中度低温体外循环对大鼠认知功能影响的初步探讨

目的　观察大鼠中度低温体外循环(CPB)后认知功能变化。方法　雄性SD大鼠随机分为CPB组(n =6 )、假CPB组(Sham组,n =4 )及单纯麻醉组(n =4 )。所有动物在咪唑安定、芬太尼麻醉后经口插管控制呼吸。CPB组和假手术对照组置入颈静脉流出管和尾动脉输入管,肝素抗凝(5 0 0U/kg)。CPB组采用中度低温CPB(2 6℃～2 8℃) ,经尾动脉灌注、颈静脉右心房-腔静脉引流,灌流量16 0ml·kg-1·min-1,总转流时间2h。Sham组除不经历CPB外,其余操作同CPB组相同,单纯麻醉组除麻醉机械通气外不经历任何手术操作。术后3d采用旷场分析(Openfieldtest )观察5min内动物的跨格次数、中央格停留时间、站立次数和排便粒数,分析术后大鼠兴奋性、紧张程度及空间认知功能变化。结果　术后3d ,CPB组大鼠兴奋性、紧张程度及空间认知功能与Sham组和单纯麻醉组相比显著降低。结论　中度低温CPB可引起大鼠认知功能损害。