Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

OBJECTIVE: Deep hypothermic circulatory arrest for neonatal heart surgery poses the risk of brain damage. Several studies suggest that pH-stat management during cardiopulmonary bypass improves neurologic outcome compared with alpha-stat management. This study compared neurologic outcome in a survival piglet model of deep hypothermic circulatory arrest between alpha-stat and pH-stat cardiopulmonary bypass. METHODS: Piglets were randomly assigned to alpha-stat (n = 7) or pH-stat (n = 7) cardiopulmonary bypass, cooled to 19 degrees C brain temperature, and subjected to 90 minutes of deep hypothermic circulatory arrest. After bypass rewarming/reperfusion, they survived 2 days. Neurologic outcome was assessed by neurologic performance (0-95, 0 = no deficit and 95 = brain death) and functional disability scores, as well as histopathology. Arterial pressure, blood gas, glucose, and brain temperature were recorded before, during, and after bypass. RESULTS: All physiologic data during cardiopulmonary bypass were similar between groups (pH-stat vs alpha-stat) except arterial pH (7.06 +/- 0.03 vs 7.43 +/- 0.09, P <.001) and arterial PCO (2) (98 +/- 8 vs 36 +/- 8 mm Hg, P <.001). No differences existed in duration of cardiopulmonary bypass or time to extubation. Performance was better in pH-stat versus alpha-stat management at 24 hours (2 +/- 3 vs 29 +/- 17, P = 0.004) and 48 hours (1 +/- 2 vs 8 +/- 9, P =.1). Also, functional disability was less severe with pH-stat management at 24 hours (P =.002) and 48 hours (P =.053). Neuronal cell damage was less severe with pH-stat versus alpha-stat in the neocortex (4% +/- 2% vs 15% +/- 7%, P <.001) and hippocampal CA1 region (11% +/- 5% vs 33% +/- 25%, P =.04), but not in the hippocampal CA3 region (3% +/- 5% vs 16% +/- 23%, P =.18) or dentate gyrus (1% +/- 1% vs 3% +/- 6%, P =.63). CONCLUSIONS: pH-stat cardiopulmonary bypass management improves neurologic outcome with deep hypothermic circulatory arrest compared with alpha-stat bypass. The mechanism of protection is not related to hemodynamics, hematocrit, glucose, or brain temperature.     

Renal hypoxanthine balance in cardiac surgery: effects of felodipine

OBJECTIVE: To test the hypothesis that felodipine, a renal vasodilator, can prevent a release of hypoxanthine during rewarming after moderate hypothermic cardiopulmonary bypass and that this is related to improved renal oxygen supply. DESIGN: A prospective, randomized, and controlled study. SETTING: Operating room in the cardiothoracic surgery department of a university hospital. PARTICIPANTS: Twenty-two patients submitted to elective first-time coronary bypass surgery. INTERVENTIONS: A catheter was placed in the left renal vein for thermodilution renal blood flow (RBF) measurement and blood sampling. In 11 patients, felodipine was infused during the hypothermic period of cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Renal uptake (renal arteriovenous concentration difference x RBF) of hypoxanthine was maintained during rewarming in felodipine-treated patients but not in control patients (55+/-28 v. -39+/-1 nmol/min, p<0.05). Oxygen consumption was higher after felodipine infusion despite unchanged total RBF. A positive correlation between renal oxygen consumption and hypoxanthine uptake and release (r = 0.74, p<0.01) was observed. CONCLUSIONS: Felodipine maintained renal uptake of hypoxanthine during rewarming after hypothermic cardiopulmonary bypass. This maintenance is the effect of improved renal oxygen supply secondary to improved nutritive blood flow at the expense of nonnutritive renal blood flow.     

Myocardial substrate uptake and oxidation during and after routine cardiac surgery.

OBJECTIVE: This study was designed to clarify whether myocardial substrate uptake and oxidation change after a period of hypothermic cardioplegic arrest during coronary artery bypass grafting procedures. METHODS: In 30 patients arterial and coronary sinus blood was sampled and coronary sinus flow measurements were performed before and after sternotomy and 10 minutes, 20 minutes, 50 minutes, and 6 hours after release of the aortic crossclamp. Measurement of free fatty acids, lactate, glucose, oxygen content, and carbon dioxide content in arterial and coronary sinus blood allowed calculations of myocardial substrate use, respiratory quotients, and myocardial oxidation rates of carbohydrates and fat. RESULTS: Uptake of free fatty acids and lactate was significant throughout the study and did not change in association with release of the crossclamp. Free fatty acid and lactate uptake measured 6 +/- 4 micromol/min and 23 +/- 26 micromol/min, respectively, before crossclamping compared with 8 +/- 7 micromol/min and 19 +/- 21 micromol/min, respectively, after release of the clamp. Glucose uptake was significant only during the first hour after crossclamp release and increased from 7 +/- 50 to 28 +/- 34 micromol/L after crossclamp release. Myocardial oxygen consumption did not change significantly (0.5 +/- 0.2 mmol/L compared with 0.35 +/- 0.2 mmol/L) after release of the crossclamp. Myocardial oxygen extraction ratio decreased from 58% +/- 8% to 41% +/- 13% after crossclamp release. Respiratory quotient increased after crossclamp release (0.85 +/- 0. 2 compared with 1.00 +/- 0.2), which implies that carbohydrate oxidation increased at the expense of free fatty acid oxidation. CONCLUSION: We conclude that hypothermic cardioplegic arrest during coronary artery bypass graft operations is associated with a transiently increased uptake and oxidation of carbohydrates during the immediate reperfusion phase.     

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia.

BACKGROUND AND OBJECTIVE: Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. METHODS: Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. RESULTS: Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 +/- 13 ng mL(-1), during bypass: 77 +/- 40 ng mL(-1); 1 h after bypass: 57 +/- 42 ng mL(-1); 6 h after bypass: 32 +/- 15 ng L(-1), 24 h after bypass; 62 +/- 21 ng mL(-1); mean +/- SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass; r=0.793, P=0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass; r=0.795, P=0.0035). CONCLUSIONS: Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.     

Correlation between cerebral and mixed venous oxygen saturation during moderate versus tepid hypothermic hemodiluted cardiopulmonary bypass

OBJECTIVE: This study was undertaken to compare cerebral oxygen saturation (RsO(2)) and mixed venous oxygen saturation (SvO(2)) in patients undergoing moderate and tepid hypothermic hemodiluted cardiopulmonary bypass (CPB). DESIGN: Prospective study. SETTINGS: University hospital operating room. PARTICIPANTS: Fourteen patients undergoing elective coronary artery bypass graft surgery using hypothermic hemodiluted CPB. INTERVENTIONS: During moderate (28 degrees -30 degrees C) and tepid hypothermic (33 degrees -34 degrees C) hemodiluted CPB, RsO(2) and SvO(2) were continuously monitored with a cerebral oximeter via a surface electrode placed on the patient's forehead and with the mixed venous oximeter integrated in the CPB machine, respectively. MEASUREMENTS AND MAIN RESULTS: Mean +/- standard deviation of RsO(2), SvO(2), PaCO(2), and hematocrit were determined prebypass and during moderate and tepid hypothermic phases of CPB while maintaining pump flow at 2.4 L/min/m(2) and mean arterial pressure in the 60- to 70-mmHg range. Compared with a prebypass value of 76.0% +/- 9.6%, RsO(2) was significantly decreased during moderate hypothermia to 58.9% +/- 6.4% and increased to 66.4% +/- 6.7% after slow rewarming to tepid hypothermia. In contrast, compared with a prebypass value of 78.6% +/- 3.3%, SvO(2) significantly increased to 84.9% +/- 3.6% during moderate hypothermia and decreased to 74.1% +/- 5.6% during tepid hypothermia. During moderate hypothermia, there was poor agreement between RsO(2) and SvO(2) with a gradient of 26%; however, during tepid hypothermia, there was a strong agreement between RsO(2) and SvO(2) with a gradient of 6%. The temperature-uncorrected PaCO(2) was maintained at the normocapnic level throughout the study, whereas the temperature-corrected PaCO(2) was significantly lower during the moderate hypothermic phase (26.8 +/- 3.1 mmHg) compared with the tepid hypothermic phase (38.9 +/- 3.7 mmHg) of CPB. There was a significant and positive correlation between RsO(2) and temperature-corrected PaCO(2) during hypothermia. CONCLUSIONS: During moderate hypothermic hemodiluted CPB, there was a significant increase of SvO(2) associated with a paradoxic decrease of RsO(2) that was attributed to the low temperature-corrected PaCO(2) values. During tepid CPB after slow rewarming, regional cerebral oxygen saturation was increased in association with an increase with the temperature-corrected PaCO(2) values. The results show that during hypothermic hemodiluted CPB using the alpha-stat strategy for carbon dioxide homeostasis, cerebral oxygen saturation is significantly higher during tepid than moderate hypothermia.     

Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

OBJECTIVES: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass. METHODS: Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass. RESULTS: The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin. CONCLUSIONS: These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.     

Superior hepatic mitochondrial oxidation-reduction state in normothermic cardiopulmonary bypass

OBJECTIVE: This study is the first comparative investigation of hepatic blood flow and oxygen metabolism during normothermic and hypothermic cardiopulmonary bypass. METHODS: Twenty-four patients undergoing coronary bypass operations were randomly divided into 2 groups according to their perfusion temperatures, either normothermia (36 degrees C) or hypothermia (30 degrees C). The clearance of indocyanine green was measured at 3 points. Arterial and hepatic venous ketone body ratios (an index of mitochondrial redox potential) and hepatic venous saturation were measured. RESULTS: Hepatic blood flow in both groups was identical before, during, and after cardiopulmonary bypass (normothermia, 499 +/- 111, 479 +/- 139, and 563 +/- 182 mL/min, respectively; hypothermia, 476 +/- 156, 491 +/- 147, and 560 +/- 202 mL/min, respectively). The hepatic venous saturation levels were significantly lower during cardiopulmonary bypass in the normothermic group (normothermia, 41% +/- 13%; hypothermia, 61% +/- 18%; P <.01), indicating a higher level of oxygen extraction use. The arterial ketone body ratio in the hypothermic group decreased severely after the onset of cardiopulmonary bypass (P <.01) and did not return to its subnormal value (>0.7) until the second postoperative day. However, the reduction in arterial ketone body ratio was less severe in the normothermic group. The difference in hepatic venous ketone body ratios was more obvious, and the hepatic venous ketone body ratios in the normothermic group were statistically superior to those of the hypothermic group throughout the course (P <.05-.01). CONCLUSIONS: Normothermic cardiopulmonary bypass provides adequate liver perfusion and results in a better hepatic mitochondrial redox potential than hypothermic cardiopulmonary bypass. Because arterial ketone body ratios reflect hepatic energy potential, normothermia was considered to be physiologically more advantageous for hepatic function.     

Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion

BACKGROUND: The purpose of this study was to compare the results of total aortic arch replacement using two different methods of brain protection, particularly with respect to neurologic outcome. METHODS: From June 1997, 60 consecutive patients who underwent total arch replacement through a midsternotomy were alternately allocated to one of two methods of brain protection: deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and postoperative (3 weeks) brain CT scan, neurological examination, and cognitive function tests were performed. Serum 100b protein was assayed before and after the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation. RESULTS: Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2 in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in 2 (6.6%) of the SCP group (p = 0.6). The incidence of transient brain dysfunction was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4, 13.3%, p = 0.05). Except in patients with strokes, S-100b values showed no significant differences in the two groups (RCP: SCP, prebypass 0.01+/-0.04: 0.05+/-0.16, postbypass 2.17+/-0.94: 1.97+/-1.00, 24 hours 0.61+/-0.36: 0.60+/-0.37, 48 hours 0.36+/-0.45: 0.46+/-0.40 microg/L, p = 0.7). There were no intergroup differences in the scores of memory decline (RCP 0.74+/-0.99; SCP 0.55+/-1.19, p = 0.6), orientation (RCP 1.11+/-1.29; SCP 0.50+/-0.76, p = 0.08), or intellectual function (RCP 1.21+/-1.27; SCP 1.05+/-1.15, p = 0.7). CONCLUSIONS: Both methods of brain protection for patients undergoing total arch replacement resulted in acceptable levels of mortality and morbidity. However, the prevalence of transient brain dysfunction was significantly higher in patients with the RCP.     

The effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest

OBJECTIVE: The purpose of this study was to determine the effects of a leukocyte-depleting filter on cerebral and renal recovery after deep hypothermic circulatory arrest. METHODS: Sixteen 1-week-old piglets underwent cardiopulmonary bypass, were cooled to 18 degrees C, and underwent 60 minutes of circulatory arrest, followed by 60 minutes of reperfusion and rewarming. Global and regional cerebral blood flow, cerebral oxygen metabolism, and renal blood flow were determined before cardiopulmonary bypass, after the institution of cardiopulmonary bypass, and at 1 hour of deep hypothermic circulatory arrest. In the study group (n = 8 piglets), a leukocyte-depleting arterial blood filter was placed in the arterial side of the cardiopulmonary bypass circuit. RESULTS: With cardiopulmonary bypass, no detectable change occurred in the cerebral blood flow, cerebral oxygen metabolism, and renal blood flow in either group, compared with before cardiopulmonary bypass. In control animals, after deep hypothermic circulatory arrest, blood flow was reduced to all regions of the brain (P <.004) and the kidneys (P =.02), compared with before deep hypothermic circulatory arrest. Cerebral oxygen metabolism was also significantly reduced to 60.1% +/- 11.3% of the value before deep hypothermic circulatory arrest (P =.001). In the leukocyte-depleting filter group, the regional cerebral blood flow after deep hypothermic circulatory arrest was reduced, compared with the value before deep hypothermic circulatory arrest (P <.01). Percentage recovery of cerebral blood flow was higher in the leukocyte filter group than in the control animals in all regions but not significantly so (P >.1). The cerebral oxygen metabolism fell to 66.0% +/- 22.3% of the level before deep hypothermic circulatory arrest, which was greater than the recovery in the control animals but not significantly so (P =.5). After deep hypothermic circulatory arrest, the renal blood flow fell to 81.0% +/- 29.5% of the value before deep hypothermic circulatory arrest (P =.06). Improvement in renal blood flow in the leukocyte filter group was not significantly greater than the recovery to 70.2% +/- 26.3% in control animals (P =.47). CONCLUSIONS: After a period of deep hypothermic circulatory arrest, there is a significant reduction in cerebral blood flow, cerebral oxygen metabolism, and renal blood flow. Leukocyte depletion with an in-line arterial filter does not appear to significantly improve these findings in the neonatal piglet.     

Neurologic monitoring for special cardiopulmonary bypass techniques

Low flow hypothermic cardiopulmonary bypass, deep hypothermic circulatory arrest, and regional low-flow cerebral perfusion are special techniques used to facilitate complex intracardiac and aortic surgery in neonates and infants. Each carries a risk of cerebral hypoxia and neurologic morbidity. Neurologic monitoring in the form of near-infrared spectroscopy for cerebral oxygenation, transcranial Doppler ultrasound, and the bispectral index electroencephalogram can monitor the brain during these techniques to determine the minimum acceptable bypass flow rates or maximum acceptable duration of deep hypothermic circulatory arrest. The use of this monitoring has the potential to improve long-term neurologic and developmental outcome.     

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.     

Hypothermic circulatory arrest is not a risk factor for neurologic morbidity in aortic surgery: a propensity score analysis

OBJECTIVE: Hypothermic circulatory arrest has been an important tool in aortic arch surgery, even though its use has recently been discussed controversially. We sought to clarify the role of hypothermic circulatory arrest as a risk factor for mortality and neurologic morbidity in aortic surgery by using a propensity score-matching analysis. METHODS: Five hundred eleven patients (60 +/- 13 years, 349 male patients) who underwent replacement of the ascending aorta with (n = 273) or without (n = 238) arch involvement were analyzed by means of multivariate analysis. Using propensity score matching, we identified comparable patient groups: HCA(+) group and HCA(-) group (n = 110 each). For aortic arch replacement, hypothermic circulatory arrest was used with a mean duration of 14 +/- 9 minutes: 12 +/- 7 minutes or 26 +/- 8 minutes for partial or total arch replacement, respectively. RESULTS: In the entire cohort multivariate analysis identified acute dissection and duration of cardiopulmonary bypass as significant predictors for hospital death. Predictors for stroke were acute dissection, diabetes mellitus, peripheral arterial disease, and concomitant mitral valve surgery, and predictors for temporary neurologic dysfunction were peripheral arterial disease and age. After propensity score matching, the incidence of death (HCA[+]: 0.9% vs HCA[-]: 2.7%), stroke (0% vs 1.8%, respectively), and temporary neurologic dysfunction (15.5% vs 13.6%, respectively) was comparable between the 2 groups. Multivariate analysis identified age, diabetes mellitus, peripheral arterial disease, and concomitant coronary artery bypass grafting as the independent risk factors for temporary neurologic dysfunction. CONCLUSIONS: In a standard clinical setting (hypothermic circulatory arrest of <30 minutes and nasopharyngeal temperature of <20 degrees C), hypothermic circulatory arrest constitutes no significant risk for mortality or neurologic morbidity and thus appears clinically safe. Patient-related risk factors primarily determine clinical outcome.     

Superior extension of intraoperative brain damage in case of normothermic systemic perfusion during coronary artery bypass operations.

OBJECTIVE: Despite the controversies on the potential detrimental effects of normothermic cardiopulmonary bypass on neurologic outcome, to date no correlation between the severity of intraoperative brain lesions and the cardiopulmonary bypass temperature used at operation has been reported. This study compares the prevalence and the severity of brain lesions in patients who underwent operation in condition of normothermic versus hypothermic systemic perfusion. METHODS: Data are derived from the analysis of 2987 consecutive primary isolated myocardial revascularizations performed at our institution between April 1990 and January 1997. Of these cases, 1385 procedures were hypothermic and 1602 procedures were normothermic systemic perfusion. In all cases the neurologic outcome and extent of ischemic areas were prospectively recorded. RESULTS: Overall, 31 patients had a perioperative stroke (1.0%). The prevalence of neurologic events was similar in the 2 groups (15 cases in the hypothermic group and 16 cases in the normothermic perfusion group; P, not significant). However, the mean Glasgow Outcome Scale score and computed tomography-demonstrated extent of brain lesions were significantly worse in the normothermic group. CONCLUSIONS: Although the prevalence of intraoperative stroke was similar with hypothermic or normothermic cardiopulmonary bypass, the use of normothermic systemic perfusion was associated with more extended brain damage at computed tomographic scan and with a worse neurologic outcome. These results demand caution in the use of normothermic cardiopulmonary bypass and claim further investigation on the neurologic safety of normothermia.     

Comparison of alpha-stat and pH-stat cardiopulmonary bypass in relation to jugular venous oxygen saturation and cerebral glucose-oxygen utilization

Jugular venous oxygen saturation (SJVO(2)) reflects the balance between cerebral blood flow and metabolism. This study was designed to compare the effects of two different acid-base strategies on jugular venous desaturation (SJVO(2) <50%) and cerebral arteriovenous oxygen-glucose use. We performed a prospective, randomized study in 52 patients undergoing cardiopulmonary bypass (CPB) at 27 degrees C with either alpha-stat (n = 26) or pH-stat (n = 26) management. A retrograde internal jugular vein catheter was inserted, and blood samples were obtained at intervals during CPB. There were no differences in preoperative variables between the groups. SJVO(2) was significantly higher in the pH-stat group (at 30 min CPB: 86.2% +/- 6.1% versus 70.6% +/- 9.3%; P < 0.001). The differences in arteriovenous oxygen and glucose were smaller in the pH-stat group (at 30 min CPB: 1.9 +/- 0.82 mL/dL versus 3.98 +/- 1.12 mL/dL; P < 0.001; and 3.67 +/- 2.8 mL/dL versus 10.1 +/- 5.2 mL/dL; P < 0.001, respectively). All episodes of desaturation occurred during rewarming, and the difference in the incidence of desaturation between the two groups was not significant. All patients left the hospital in good condition. Compared with alpha-stat, the pH-stat strategy promotes an increase in SJVO(2) and a decrease in arteriovenous oxygen and arteriovenous glucose differences. These findings indicate an increased cerebral supply with pH-stat; however, this strategy does not eliminate jugular venous desaturation during CPB. IMPLICATIONS: A prospective, randomized study in 52 patients during cardiopulmonary bypass revealed that pH-stat increased jugular venous oxygen saturation and decreased arteriovenous oxygen-glucose differences. There was no difference in the incidence of jugular venous desaturation. These findings suggest an increased cerebral blood flow with no protection against jugular venous desaturation during pH-stat.     

The influence of pH strategy on cerebral and collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease: results of a randomized trial and real-time monitoring

OBJECTIVE: The optimal pH strategy during hypothermic cardiopulmonary bypass remains controversial. Systemic pulmonary collateral circulation may develop in patients with cyanotic anomalies. The purpose of this study was to evaluate the effect of pH strategies on cerebral oxygenation and systemic pulmonary collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. METHODS: Forty cyanotic patients (age > 1 year) with heart disease were prospectively randomized into 2 groups. Group 1 (n = 19, 14.3 +/- 1.5 kg) underwent hypothermic cardiopulmonary bypass with alpha-stat strategy and group 2 (n = 21, 12.5 +/- 0.9 kg) with pH-stat. Cardiopulmonary bypass was established with pump-assisted drainage. Cerebral oxygenation was assessed by near-infrared spectroscopy and the systemic pulmonary collateral circulation was calculated by pump flows [% systemic pulmonary collateral circulation = perfusion flow - drainage flow)/perfusion flow x 100]. Lactate was measured as an index of systemic anaerobic metabolism. RESULTS: There were no significant differences in preoperative hematocrit, oxygen saturation, Qp/Qs, cardiopulmonary bypass duration, minimum temperatures, perfusion flow and pressure, urine output, and depth of anesthesia between the groups. Oxyhemoglobin signal and tissue oxygenation index of near-infrared spectroscopy monitoring were significantly lower in group 1 compared with group 2 (P =.008 and P <.0001, respectively), suggesting inadequate cerebral oxygenation with alpha-stat. Deoxygenated hemoglobin signal was significantly higher in group 1 relative to group 2 (P <.0001). The % systemic pulmonary collateral circulation was significantly lower in group 2 compared with group 1, suggesting a reduced pulmonary collateral circulation with pH-stat (P <.0001, average; group 1, 20.1% +/- 1.2%; group 2; 7.7% +/- 0.7%). Serum lactate was significantly lower in group 2 (P <.0001). CONCLUSIONS: The pH-stat strategy results in an improved environment, including sufficient cerebral oxygenation, decreased systemic pulmonary collateral circulation, and lower lactate level during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. Future studies should investigate the long-term neurological outcome.     

Change in plasma glutamate concentration during cardiac surgery is a poor predictor of cognitive outcome

OBJECTIVE: To develop a simple and reliable method for quantitating plasma glutamate concentration and apply this method to monitor systemic glutamate levels during coronary artery bypass graft (CABG) surgery, a procedure associated with neurologic deficits. DESIGN: Prospective serial investigation of cardiac surgery patients. SETTING: Tertiary-care university teaching hospital. PARTICIPANTS: Patients undergoing CABG surgery (n = 33). INTERVENTIONS: Preoperative and postoperative neurologic and neurocognitive testing were done. Intraoperative blood samples for glutamate quantitation were obtained from jugular bulb and pulmonary artery catheters before, during, and after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Glutamate concentrations were determined using a reverse-phase high-pressure liquid chromatography method coupled to precolumn derivatization of the analyte with o-phthalaldehyde. The mean prebypass plasma glutamate concentration was 79.4 +/- 41.8 micromol/L. Plasma glutamate levels fluctuated during surgery with considerable degrees of temporal and quantitative interpatient variability. Neurologic and neurocognitive deficits were observed after CABG surgery. However, neither the occurrence nor the severity of cognitive decline could be predicted by the magnitude of increase in plasma glutamate concentration. CONCLUSION: Fluctuations in intraoperative systemic glutamate levels do not predict post-CABG surgery neurologic outcome.     

Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic left heart syndrome using continuous regional cerebral perfusion

OBJECTIVES: Stage 1 palliation of hypoplastic left heart syndrome requires the interruption of whole-body perfusion. Delayed reflow in the cerebral circulation secondary to prolonged elevation in vascular resistance occurs in neonates after deep hypothermic circulatory arrest. We examined relative changes in cerebral and somatic oxygenation with near-infrared spectroscopy while using a modified perfusion strategy that allowed continuous cerebral perfusion. METHODS: Nine neonates undergoing stage 1 palliation for hypoplastic left heart syndrome had regional tissue oxygenation continuously measured by frontal cerebral and thoraco-lumbar (T10-L2) somatic (renal) reflectance oximetry probes (rSO(2), INVOS; Somanetics, Troy, Mich). Surgery was accomplished using cardiopulmonary bypass with whole-body cooling (18 degrees C-20 degrees C) and regional cerebral perfusion through the innominate artery at flow rates guided by estimated minimum flow requirements and measured rSO(2) during reconstruction of the aortic arch. Data were logged at 1-minute intervals and analyzed using repeated measures analysis of variance. RESULTS: A total of 3176 minutes of data were analyzed. Prebypass cerebral rSO(2) was 65.4 +/- 8.9, and somatic rSO(2) was 58.9 +/- 12.4 (P <.001, cerebral vs somatic). During regional cerebral perfusion, cerebral rSO(2) was 80.7 +/- 8.6, and somatic rSO(2) was 41.4 +/- 7.1 (P <.001). Postbypass cerebral rSO(2) was 53.2 +/- 14.9, and somatic rSO(2) was 76.4 +/- 7.7 (P <.001). The risk of cerebral desaturation was significantly increased after cardiopulmonary bypass. CONCLUSIONS: Cerebral oxygenation was maintained during regional cerebral perfusion at prebypass levels with deep hypothermia. However, after rewarming and separation from cardiopulmonary bypass, cerebral oxygenation was lower compared with prebypass or somatic values. These results indicate that cerebrovascular resistance is increased after deep hypothermic cardiopulmonary bypass, even with continuous perfusion techniques, placing the cerebral circulation at risk postoperatively.     

The effect of hematocrit on cerebral blood flow velocity in neonates and infants undergoing deep hypothermic cardiopulmonary bypass.

Varying degrees of hemodilution are used during deep hypothermic cardiopulmonary bypass. However, the optimal hematocrit (Hct) level to ensure adequate oxygen delivery without impairing microcirculatory flow is not known. In this prospective, randomized study, cerebral blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography in 35 neonates and infants undergoing surgery with deep hypothermic cardiopulmonary bypass. Patients were randomized to low Hct (aiming for 20%) or high Hct (aiming for 30%) during cooling on cardiopulmonary bypass (CPB). Systolic (V(s)), mean (Vm), and diastolic (Vd) cerebral blood flow velocity, as well as pulsatility index (PI = [V(s) - Vd]/Vm) and resistance index (RI = [V(s) - Vd]/V(s)) were recorded at six time points: postinduction, at cannulation, after 10 min cooling on CPB, rewarmed to 35 degrees C on CPB, immediately off CPB, and at skin closure. Vm was significantly lower in the high Hct group compared with that in the low Hct group during cooling (P < 0.01). Postinduction, the high Hct group demonstrated significantly lower Vd immediately off CPB (P < 0.01) and significantly lower Vm and V(s) at skin closure (P < 0.001). We conclude that there is an inverse relation between hematocrit and cerebral blood flow velocity during deep hypothermic cardiopulmonary bypass in neonates and infants. Implications: There is an inverse relation between hematocrit and cerebral blood flow velocity during deep hypothermic cardiopulmonary bypass in neonates and infants. Further studies correlating Hct and cerebral blood flow velocity with cerebral metabolic rate and neurologic outcome are necessary to determine the optimal Hct during deep hypothermic cardiopulmonary bypass.     

Comparison of pH-state and Alpha-stat Cardiopulmonary Bypass on Cerebral Oxygenation and Blood Flow in Relation to Hypothermic Circulatory Arrest in Piglets

Background: Deep hypothermic circulatory arrest is used in neonatal cardiac surgery. Recent work has suggested improved neurologic recovery after deep hypothermic arrest with pH-stat cardiopulmonary bypass (CPB) compared with alpha-stat CPB. This study examined cortical oxygen saturation (ScO(2)), cortical blood flow (CBF), and cortical physiologic recovery in relation to deep hypothermic arrest with alpha-stat or pH-stat CPB.

Methods: Sixteen piglets were cooled with pH-stat or alpha-stat CPB to 19 [degree sign]C (cortex) and subjected to 60 min of circulatory arrest, followed by CPB reperfusion and rewarming and separation from CPB. Near infrared spectroscopy and laser Doppler flowmetry were used to monitor ScO(2) and CBF. Cortical physiologic recovery was assessed 2 h after the piglets were separated from CPB by cortical adenosine triphosphate concentrations, cortical water content, CBF, and ScO(2).

Results: During CPB cooling, ScO(2) increased more with pH-stat than with alpha-stat bypass (123 +/- 33% vs. 80 +/- 25%); superficial and deep CBF were also greater with pH-stat than with alpha-stat bypass (22 +/- 25% vs. -56 +/- 22%, 3 +/- 19% vs. -29 +/- 28%). During arrest, ScO(2) half-life was greater with pH-stat than with alpha-stat bypass (10 +/- 2 min vs. 7 +/- 2 min), and cortical oxygen consumption lasted longer with pH-stat than with alpha-stat bypass (36 +/- 8 min vs. 25 +/- 8 min). During CPB reperfusion, superficial and deep CBF were less with alpha-stat than with pH-stat bypass (-40 +/- 22% vs. 10 +/- 39%, -38 +/- 28% vs. 5 +/- 28%). After CPB, deep cortical adenosine triphosphate and CBF were less with alpha-stat than with pH-stat bypass (11 +/- 6 pmole/mg vs. 17 +/- 8 pmole/mg, -24 +/- 16% vs. 16 +/- 32%); cortical water content was greater with alpha-stat than with pH-stat bypass (superficial: 82.4 +/- 0.3% vs. 81.8 +/- 1%, deep: 79.1 +/- 2% vs. 78 +/- 1.6%).     

Cardiopulmonary bypass and the blood-brain barrier. An experimental study.

The diffuse inflammation produced by cardiopulmonary bypass might disrupt the blood-brain barrier and lead to the transient neurologic dysfunction occasionally seen after cardiac operations. To evaluate this possibility, blood-brain barrier integrity was measured by carbon 14-aminoisobutyric acid tracer technique after 2 hours of cardiopulmonary bypass in piglets. Six animals were cooled to 28 degrees C on cardiopulmonary bypass and then rewarmed to 38 degrees C before carbon 14-aminosisobutyric acid was injected intraarterially. A control group of six animals underwent median sternotomy and heparinization but were not placed on cardiopulmonary bypass. Blood-to-brain transfer coefficients for carbon 14-aminosisobutyric acid were calculated for multiple brain regions; higher coefficients reflect greater flux of carbon 14-aminosisobutyric acid and suggest loss of blood-brain barrier integrity. The brain regions examined and their transfer coefficients (cardiopulmonary bypass versus control mean +/- standard error of the mean ml/gm/min) were middle cerebral artery territory cortex (0.0032 +/- 0.0002 versus 0.0030 +/- 0.0002; p = 0.42), diencephalon (0.0031 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.50), midbrain (0.0028 +/- 0.0002 versus 0.0027 +/- 0.0002; p = 0.86), cerebellum (0.0036 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.22), and spinal cord (0.0035 +/- 0.0003 versus 0.0041 +/- 0.0008; p = 0.48). There were no significant differences in transfer coefficients between animals placed on cardiopulmonary bypass and control animals in any brain region examined. The pituitary gland lacks a blood-brain barrier and had a correspondingly high coefficient in control animals and those undergoing cardiopulmonary bypass (0.077 +/- 0.012 versus 0.048 +/- 0.008; p = 0.07). Two hours of moderately hypothermic cardiopulmonary bypass does not disrupt the blood-brain barrier.