Assessment of cerebral oxygen balance during deep hypothermic circulatory arrest by continuous jugular bulb venous saturation and near-infrared spectroscopy

OBJECTIVE: The purpose of this study was to compare jugular venous bulb saturation (SjvO(2)) and regional cerebral oximetry (rSO(2)) by near-infrared spectroscopy (NIRS) during procedures with deep hypothermic circulatory arrest (DHCA). DESIGN: Prospective observational study. SETTING: Academic hospital. PARTICIPANTS: Patients undergoing aortic reconstructive surgery with DHCA from July 2001 to January 2005. INTERVENTION: The authors examined cerebral oxygenation by continuous NIRS monitoring and by blood gas analysis of intermittently sampled jugular bulb blood (SjvO(2)). Data were obtained during various stages of the procedure in 29 patients. NIRS measurements were compared with SjvO(2). MEASUREMENTS AND MAIN RESULTS: NIRS and SjvO(2) trends were similar. Overall, cerebral venous oxygen saturation obtained from NIRS was lower compared with SjvO(2) (p < 0.05), especially during periods of low temperature. The mean correlation between NIRS and SjvO(2) was 0.363, and the individual correlations varied from -0.11 to 0.91. The low mean correlation was because of a high degree of variability in the NIRS data between patients. CONCLUSION: It was concluded that NIRS does not closely correlate with SjvO(2) in this patient population. Cerebral oximetry measured by NIRS could not replace jugular bulb saturation as an intraoperative marker of adequate metabolic suppression.     

Modified ultrafiltration may not improve neurologic outcome following deep hypothermic circulatory arrest.

OBJECTIVE: Modified ultrafiltration (MUF) improves systolic blood pressure and left ventricular performance, as well as lowering transfusion requirements, after cardiopulmonary bypass (CPB). MUF has also been shown to enhance acute cerebral metabolic recovery after deep hypothermic circulatory arrest (DHCA), but whether this improves neurologic outcome is unknown. METHODS: Sixteen neonatal piglets underwent CPB and 90 min of DHCA. The hematocrit was maintained between 25 and 30%. Alpha-stat blood gas management was used. After separation from CPB, animals were randomized to 15 min of MUF (n = 8) or no intervention (n = 8). Neurologic injury was assessed with behavior scores and histologic examination. Standardized behavior scores were obtained on post-operative days 1, 3, and 6 (0 = no deficit to 95 = brain death). The percentage of injured neurons by hematoxylin and eosin staining and the degree of reactive astrocytosis by glial filbrillary acidic protein (GFAP) immunohistochemistry were assessed to determine histologic scores in the neocortex and hippocampus (0 = no injury to 4 = diffuse injury). RESULTS: There were no statistically significant differences between groups during CPB. After MUF, the hematocrit was significantly higher (40% +/- 5.7 vs. 28% +/- 3.9, P < 0.001). There were no significant differences in behavior scores between groups (p > 0.1). There was resolution of deficits by day 6 in all animals. Neuronal injury was present in 81% (13/16) of the animals with no statistically significant differences between groups in incidence or severity. CONCLUSIONS: Use of MUF after DHCA does not prevent neuronal injury or improve neurologic outcome in this neonatal swine model.     

Kinetics of cerebral deoxygenation during deep hypothermic circulatory arrest in neonates.

Brain injury associated with neonatal congenital heart operations performed during deep hypothermia and/or total circulatory arrest is often attributed to cerebral hypoxia. We studied the kinetic changes in cerebrovascular hemoglobin O2 saturation (HbO2%) and total hemoglobin concentration (Hbtotal) in 17 neonates undergoing cardiac surgery as they were cooled to 15 degrees C, underwent total circulatory arrest, and were rewarmed. HbO2% and Hbtotal in brain vasculature were monitored noninvasively by near-infrared spectroscopy. Neonates were cooled over 12 min and rewarmed over 15 min while being perfused using cardiopulmonary bypass (CPB). Total circulatory arrest lasted from 20 to 70 min. We found that HbO2% in brain vasculature increased during the initial 8 min of CPB as nasopharyngeal temperature decreased, and then remained constant until circulatory arrest. After the onset of circulatory arrest, cerebrovascular HbO2% decreased curvilinearly for 40 min; no further hemoglobin desaturation was observed from 40 to 70 min of arrest. The changes in cerebrovascular Hbtotal were quite different from those in HbO2%, as Hbtotal decreased during the initial minute of CPB and circulatory arrest and then remained constant until recirculation. Brain intravascular HbO2% and Hbtotal increased within 3 min after the onset of recirculation to prearrest levels, and during rewarming, HbO2% decreased to normothermic baseline values. The results demonstrate that cerebral oxygenation increased during CPB cooling; O2 was consumed by the neonatal brain during the initial 40 min of deep hypothermic circulatory arrest; and cerebral oxygenation was restored on recirculation. These observations may be important in identifying the etiologies of brain injury during neonatal congenital heart surgery.     

The postoperative care of adult patients exposed to deep hypothermic circulatory arrest

Deep hypothermic circulatory arrest with cardiopulmonary bypass is indicated for complex surgical operations in adult patients involving the aortic arch, thoracoabdominal aorta, cerebral vasculature, and tumors extending into the vena cava and heart. Understanding the principles of ischemic-reperfusion injury and the effects of hypothermia in attenuating this process is fundamental to the delivery of effective postoperative care. Neurologic injury is the most troublesome adverse effect after the use of deep hypothermic circulatory arrest and cardiopulmonary bypass, presenting as either a transient neurologic deficit (5.9% to 28.1%) or an irreversible neurologic injury (1.8% to 13.6%). In patients with neurological injury, early postoperative mortality is markedly increased (18.2%), and for those patients that survive, long-term cognitive disability is still evident 6 months later. Early postoperative support of organ function, along with timely diagnosis and treatment of organ injury, is essential in minimizing perioperative morbidity, particularly neurologic morbidity. Meticulous management of fluids, maintaining stable cardiovascular hemodynamics with particular attention to systolic blood pressure, optimizing oxygen delivery, limiting ventilator-associated lung injury, intensive insulin therapy for control of blood glucose levels, and avoidance of hyperthermia are essential in limiting organ injury and reducing perioperative morbidity and mortality.     

Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermic circulatory arrest.

OBJECTIVE: The aim of this study was to assess the effects of preoperative high dose methylprednisolone on cerebral recovery following a period of deep hypothermic circulatory arrest (DHCA). METHODS: Sixteen 1-week-old piglets were randomized to placebo (n=8), or 30 mg/kg intramuscular methylprednisolone sodium succinate (MPRED) given at 8 and 2 h before induction of anaesthesia. All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 min of circulatory arrest followed by 60 min of reperfusion and rewarming. The radiolabelled microsphere method was used to determine the global and regional cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) at baseline before DHCA and after 60 min of reperfusion. RESULTS: In controls, mean global CBF (+/-1 standard error) before DHCA was 53.7+/-2.4 ml/100 g per min and fell to 23.8+/-1.2 ml/100 g per min following DHCA (P<0.0001). This represents a post-DHCA recovery to 45.1+/-3.3% of the pre-DHCA value. In the MPRED group recovery of global CBF post-DHCA was significantly higher at 63.6+/-5.2% of the pre-DHCA value (P=0.009). The regional recovery of CBF in the cerebellum, brainstem and basal ganglia was 80, 75 and 69% of pre-DHCA values in the MPRED group respectively compared to 66, 60 and 55% in controls (P<0.05). Global CMRO(2) in controls fell from 3.9+/-0.2 ml/100 g per min before to 2. 3+/-0.2 ml/100 g per min after DHCA (P=0.0001). This represents a post-DHCA recovery to 58.6+/-4.4% of the pre-DHCA value. In the MPRED group, however, recovery of global CMRO(2) post-DHCA was significantly higher at 77.9+/-7.1% of the pre-DHCA value (P=0.04). CONCLUSIONS: Treatment with high dose methylprednisolone at 8 and 2 h preoperatively attenuates the normal cerebral response to a period of deep hypothermic ischaemia. This technique may therefore offer a safe and inexpensive strategy for cerebral protection during repair of congenital heart defects with the use of DHCA.     

The impact of deep and moderate body temperatures on end-organ function during hypothermic circulatory arrest

Objective: Hypothermic circulatory arrest (HCA) at different temperatures is a protection technique for operations involving the aortic arch. In combination with selective cerebral perfusion, higher arrest temperatures for the remaining body may be permitted. However, the ischaemic/reperfusion injury (I/R) in various organ systems, other than the brain, related to the specific HCA temperature has so far not been evaluated. Methods: Fourteen pigs were randomly assigned to 60 min of sole HCA at 20 or 30 °C temperature, weaned from cardiopulmonary bypass (CPB) and followed 4 h after HCA. Besides complex haemodynamic monitoring, laser-Doppler spectrophotometry for measuring capillary blood flow, tissue oxygen saturation and post-capillary venous filling pressures of the bowel was installed. At the end of experiment, organs were perfusion fixated and harvested. Results: During the entire experiment, haemodynamics revealed no differences between the groups. CPB bypass times were 177 ± 12 min in the 20 °C and 158 ± 11 min in the 30 °C group, respectively (p = 0.02). During reperfusion, lactate levels were initially significantly higher in the 30 °C animals (p = 0.001) but subsequently declined. Microcirculatory blood flow and velocity in the bowel were significantly reduced during cooling and reperfusion (p < 0.05), but were independent of final HCA temperature. Histological evaluation revealed significantly more oedema formation in the bowel wall of the 30 °C animals (p = 0.05). Conclusions: Higher levels of circulating lactate levels during reperfusion indicate less effective organ protection at 30 than at 20 °C after 60 min of HCA. This is further substantiated by histological evidence for a more pronounced oedema inflammatory response within the bowel wall.     

Hippocampal neuronal death following deep hypothermic circulatory arrest in dogs: involvement of apoptosis.

This study was undertaken to evaluate the histological nature of brain damage caused by deep hypothermic circulatory arrest during cardiopulmonary bypass. Total body cooling to 15 degrees C and rewarming were performed with a conventional cardiopulmonary bypass technique using the femoral artery and vein. Dogs were assigned to one of three groups. In group 1 (n = 4), cardiopulmonary bypass was maintained in a state of deep hypothermia (15 degrees C) for 90 min, group 2 animals (n = 5) underwent 60 min of deep hypothermic circulatory arrest at 15 degrees C, and group 3 (n = 6) underwent 90 min of deep hypothermic circulatory arrest at 15 degrees C. All dogs were killed by perfusion fixation 72 h after cardiopulmonary bypass. The CA1 regions of the hippocampi were examined by light and electron microscopy. Biotinylated dUTP was used for nick-end labeling of apoptotic cells mediated by terminal deoxytransferase. No morphological change was observed in group 1 dogs, and very little in group 2 dogs. More severe neuronal damage was observed in group 3. The nuclei of many cells were shrunken and showed nick-end labeling. Dense chromatin masses were detected electron microscopically in the nuclei of CA1 pyramidal cells. Neuronal cell death observed in CA1 pyramidal cells 72 h after 90 min of deep hypothermic circulatory arrest at 15 degrees C involves apoptosis. Therefore, according to this model, the maximum duration of deep hypothermic circulatory arrest should not be allowed to exceed 60 min.     

Quality of life after interventions on the thoracic aorta with deep hypothermic circulatory arrest.

OBJECTIVE: Assessment of quality of life (QL) in patients undergoing major surgical procedures is of increasing interest. We focused on surgery of the thoracic aorta requiring deep hypothermic circulatory arrest (DHCA). Aim of this study was to assess QL after thoracic aortic surgery with DHCA, using the Short Form 36 Health Survey (SF-36) questionnaire. METHODS: Between 01/94 and 12/99 212 (59.1%) out of a total of 359 interventions on the thoracic aorta were performed under DHCA, with an early mortality of 13.7% (28 patients). During an average follow-up of 3.2+/-1.3 years, 27 patients died (15.2%) and five patients (2.8%) were lost. A total of 145 patients (81.9%) had a complete follow-up. RESULTS: 125 of the 145 SF-36 questionnaire handed out were answered correctly (86.2%). In relation to a standard population (z=0), the most important deficits were found in physical function (z=-0.53) and role limitations because of physical health (z=-0.42). Good results were found regarding the aspect of pain (z=0.28), social functioning (z=0.02) and vitality (z=-0.02). Overall QL in patients having been operated for aortic aneurysm was better than for patients with acute type A-dissection. CONCLUSION: Despite restrictions in physical functioning and role limitation because of physical health, QL in patients after interventions on the thoracic aorta with DHCA is fairly good and, for patients being operated for aortic aneurysm, comparable to an age-matched standard population. Patients having being operated electively for aortic aneurysm enjoyed a better QL than patients having been operated emergently for acute type A dissection.     

Using reagent-supported thromboelastometry (ROTEM((R))) to monitor haemostatic changes in congenital heart surgery employing deep hypothermic circulatory arrest

Objective: Cardiac surgery employing cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) can induce coagulation disturbances and bleeding complications that may be especially severe in infants. A better understanding of the coagulopathy and a quick method for its evaluation would be helpful in the management of patients exposed to CPB and DHCA. This study aimed to monitor coagulation defects in congenital heart surgery using rotational thromboelastometry (ROTEM((R))), standard coagulation tests and platelet flow cytometry. Methods: The study comprised 10 infants undergoing surgery for congenital heart disease on CPB and DHCA. Blood was sampled at skin incision, after heparinisation during CPB (directly pre- and directly post-DHCA) and after protamine administration post-CPB. ROTEM((R)) using different reagents including a heparinase-containing assay to evaluate coagulation during heparinisation, APTT and INR, and flow cytometry to evaluate platelet activation were performed. Results: During CPB, the ROTEM((R)) indicated CPB-induced clotting factor depletion and platelet dysfunction that persisted after CPB and heparin neutralisation. ROTEM((R)) results were available within 15min and therefore much faster than standard tests. ROTEM((R))-guided specific blood product treatment resulted in satisfactory coagulatory function. The highest degree of platelet activation was found directly after DHCA. Conclusions: A major benefit of ROTEM((R)) is the quick detection of a developing coagulopathy already during CPB. ROTEM((R)) guides quick and specific blood product treatment after CPB, which may decrease bleeding complications in cardiac surgery. The finding of maximal platelet activation directly after DHCA suggests that not only CPB but also hypothermia activates platelets in vivo, thereby contributing to platelet dysfunction.     

Repair of acute mediastinoscopic injury to the pulmonary artery using an intravascular approach and deep hypothermic circulatory arrest

A potentially serious but rare complication of mediastinoscopy procedures is acute damage to any of the great vessels in the region of the distal trachea and carina. We report a case of serious hemorrhage from a mediastinoscopic biopsy-injury to the posterior aspects of the right pulmonary artery (RPA), which required sternotomy, cardiopulmonary bypass, division and retraction of the ascending aorta, incision of the RPA, intermittent deep hypothermic circulatory arrest, and suturing from the inside of the RPA for a successful repair.     

Comparison of metabolic responses to deep hypothermic total circulatory arrest and retrograde cerebral perfusion in an experimental model

An experimental study was designed to search the effectiveness of retrograde cerebral perfusion which is presently used as cerebral protection method for the surgery of arcus aorta. Twelve dogs were subjected to the study. Six of them were remained in total circulatory arrest at 20 degrees C for 60 min. Retrograde cerebral perfusion was done again at 20 degrees C for 1 h for the other six dogs.Tumor necrosis factor (TNF), P-selectin, Intracellular Adhesion Molecule (ICAM), Creatine Phosphokinase (CPK-BB) and tissue Adenosine triphosphate (ATP) levels were measured, before the cardiopulmonary bypass at 37 degrees C and during perfusion period at 5, 60 min and 4 h.Tissue ATP level for retrograde cerebral perfusion group was 3.99+/-0.7 mcmol/g tissue and 2.86+/-0.1 mcmol/g tissue for total circulatory arrest group at fourth hour (p<0.05). TNF level was significantly higher in total circulatory arrest group than retrograde cerebral perfusion group (p<0.05). The samples taken at fourth hour of reperfusion showed the TNF level was, 162.55+/-13.1 pcg/ml for total circulatory arrest group and this value was 12.5+/-3.4 pcg/ml for retrograde cerebral perfusion group.ICAM (Intracellular Adhesion Molecule) level was higher in total circulatory arrest group (18.75+/-3.6 ng/ml) when compared to retrograde cerebral perfusion group (8.75+/-1.8 ng/ml) (p<0.05).All parameters showed that retrograde cerebral perfusion preserved the brain functions better comparing with total circulatory arrest. The time necessary for aortic surgery may be provided by the retrograde cerebral perfusion technique.     

Hypothermic circulatory arrest does not increase the risk of ascending thoracic aortic aneurysm resection.

OBJECTIVE: The purpose of this study was to investigate the safety and efficacy of a period of deep hypothermic circulatory arrest (DHCA) during elective replacement of the ascending thoracic aorta. SUMMARY BACKGROUND DATA: DHCA has been implemented in ascending thoracic aortic aneurysm resection whenever the anatomy or pathology of the aorta or arch vessels prevents safe or adequate cross-clamping. Profound hypothermia and retrograde cerebral perfusion have been shown to be neurologically protective during ascending aortic replacement under circulatory arrest. METHODS: The authors conducted a retrospective analysis of 91 consecutive patients who underwent repair of chronic ascending thoracic aortic aneurysms from 1986 to present. The authors hypothesized that patients undergoing DHCA with or without retrograde cerebral perfusion during aneurysm repair were at no greater operative risk than patients who received aneurysm resection while on standard cardiopulmonary bypass. RESULTS: There were no significant differences in hospital mortality, stroke rate, or operative morbidity between patients repaired on DHCA when compared to those repaired on cardiopulmonary bypass. CONCLUSIONS: DHCA with or without retrograde cerebral perfusion does not result in increased morbidity or mortality during the resection of ascending thoracic aortic aneurysms. In fact, this technique may prevent damage to the arch vessels in select cases and avoid the possible complications associated with cross-clamping a friable or atherosclerotic aorta.     

外源性牛磺酸对兔深低温停循环术中脑海马区兴奋性氨基酸的影响

目的　观察兔深低温停循环手术中海马区兴奋性氨基酸 (EAA)的变化及外源性牛磺酸对其影响。方法　将 16只成年新西兰白兔随机分为对照组和治疗组,每组 8只,治疗组在建立体外循环前静脉给予牛磺酸 150mg/kg,建立埋植脑微透析装置的体外循环和深低温停循环模型,平衡透析 2h后每 30min取脑海马区细胞间液 1次。采用高效液相色谱紫外检测法,测定兔在麻醉状态、体外循环降温过程中、深低温停循环前 30min、深低温停循环后 30min、复温前 30min、复温后 30min时脑细胞间液中谷氨酸、天门冬氨酸、甘氨酸、牛磺酸的水平变化。结果　对照组谷氨酸在复温前30min、复温后 30min分别是静息状态 ( 5. 1±1 .5 )和 ( 4. 1±1. 4 )倍,高于治疗组的 ( 2 1±1 5 )和(1 1±0 4)倍(t=3 .74, 5. 45,P均<0 .01)。对照组甘氨酸在深低温停循环后 30min为静息状态的6. 7(3. 6, 13. 6)倍,高于治疗组的 4. 2 (3. 8, 11. 5)倍 (T=75 00,P<0. 05)。治疗组的牛磺酸在深低温停循环后 30min时为静息状态的 6. 9(3. 0, 14. 2)倍,高于对照组的 4. 0 (3. 0, 5. 7)倍 (T=75. 00,P<0. 05),复温前 30min时为静息状态的 10. 6 ( 2. 8, 22. 5 )倍,高于对照组的 3. 2 ( 1. 2, 7. 6 )倍(T=90. 00,P<0. 05)。天门冬氨酸在两组间比较差异无统计学意     

深低温停循环下兔脑内兴奋性氨基酸的早期变化与脑损伤研究

目的　探讨体外循环(CPB)和深低温停循环(DHCA)下脑内兴奋性氨基酸(EAA )早期变化规律,及其“兴奋毒性”作用在脑损伤中的作用。方法　建立应用脑微透析技术的兔CPB和DHCA模型。利用高效液相的电化学检测方法,测定兔脑海马CA1区脑细胞间液中EAA的连续性变化。术后利用透射电子显微镜给予组织学损伤评分。结果　谷氨酸在CPB组各阶段变化差异无统计学意义(P >0 .0 5 ) ;DHCA组在恢复循环早期明显升高(P <0 .0 5 ) ,升高程度DHCA组明显高于CPB组(P <0 .0 1)。天冬氨酸在DHCA组恢复灌注3 0～60min阶段明显升高(P <0 .0 1) ,但与CPB组的组间对照差异无统计学意义(P >0 .0 5 )。透射电镜发现两组脑细胞超微结构均明显损伤,DHCA组损伤重于C组(P <0 .0 5 )。结论　“兴奋毒性”作用与中低温CPB造成的脑损伤无关。DHCA可使再灌注早期兴奋性氨基酸升高,并导致脑损伤加重