Response of cerebral blood flow to phenylephrine infusion during hypothermic cardiopulmonary bypass: influence of PaCO2 management

Twenty-eight adult patients anesthetized with fentanyl, then subjected to hypothermic cardiopulmonary bypass (CPB), were studied to determine the effect of phenylephrine-induced changes in mean arterial pressure (MAP) on cerebral blood flow (CBF). During CPB patients managed at 28 degrees C with either alpha-stat (temperature-uncorrected PaCO2 = 41 +/- 4 mmHg) or pH-stat (temperature-uncorrected PaCO2 = 54 +/- 8 mmHg) PaCO2 for blood gas maintenance received phenylephrine to increase MAP greater than or equal to 25% (group A, n = 10; group B, n = 6). To correct for a spontaneous, time-related decline in CBF observed during CPB, two additional groups of patients undergoing CPB were either managed with the alpha-stat or pH-stat approach, but neither group received phenylephrine and MAP remained unchanged in both groups (group C, n = 6; group D, n = 6). For all patients controlled variables (nasopharyngeal temperature, PaCO2, pump flow, and hematocrit) remained unchanged between measurements. Phenylephrine data were corrected based on the data from groups C and D for the effect of diminishing CBF over time during CPB. In patients in group A CBF was unchanged as MAP rose from 56 +/- 7 to 84 +/- 8 mmHg. In patients in group B CBF increased 41% as MAP rose from 53 +/- 8 to 77 +/- 9 mmHg (P less than 0.001). During hypothermic CPB normocarbia maintained via the alpha-stat approach at a temperature-uncorrected PaCO2 of approximately equal to 40 mmHg preserves cerebral autoregulation; pH-stat management (PaCO2 approximately equal to 57 mmHg uncorrected for temperature, or 40 mmHg when corrected to 28 degrees C) causes cerebrovascular changes (i.e., impaired autoregulation) similar to those changes produced by hypercarbia in awake, normothermic patients.     

Differences in cerebral blood flow between alpha-stat and pH-stat management are eliminated during periods of decreased systemic flow and pressure. A study during cardiopulmonary bypass in rabbits

Prior reports suggest cerebral blood flow (CBF) responses to changing bypass (systemic) flow rates may differ between alpha-stat and pH-stat management. To compare the effect of blood gas management upon CBF responses to changing systemic flow and pressure, 15 New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent nonpulsatile cardiopulmonary bypass at 25 degrees C. One group of animals (n = 8) was randomized to alpha-stat blood gas management that maintained arterial carbon dioxide tension (PaCO2) approximately 40 mmHg when measured at 37 degrees C. A second group (n = 7) was managed with pH-stat technique, maintaining PaCO2 approximately 40 mmHg when corrected to the animal's actual temperature. Bypass was initiated at a flow rate of 100 ml.kg-1.min-1 and, after approximately 20 min, control hemodynamic and CBF measurements (radioactive microspheres) were made. Thereafter, bypass flow rate was changed in random order at 15-min intervals to 50, 70, and 100 ml.kg-1.min-1. CBF and hemodynamic measurements were repeated at the end of each period of altered bypass flow. Groups differed significantly with respect to both pHa and PaCO2. There were no significant differences between groups with respect to bypass flow rate, mean arterial pressure (MAP), central venous pressure, temperature, hematocrit, arterial oxygen tension (PaCO2), or bypass duration at any measurement point. MAP decreased significantly, from approximately 80 to approximately 65 mmHg with decreasing bypass flow (P = 0.0001). Over the entire range of bypass flows, CBF decreased with decreasing bypass flow (P = 0.001), and the degree of change was equivalent among regions and between groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension

Cerebral blood flow (radioactive microspheres), intracranial pressure (subdural bolt), and retinal histopathology were examined in 20 dogs undergoing 150 minutes of hypothermic (28 degrees C) cardiopulmonary bypass to compare alpha-stat (arterial carbon dioxide tension, 40 +/- 1 mm Hg; n = 10) and pH-stat (arterial carbon dioxide tension, 61 +/- 1 mm Hg; n = 10) techniques of arterial carbon dioxide tension management. Pump flow (80 mL.kg-1.min-1), mean aortic pressure (78 +/- 2 mm Hg), and hemoglobin level (87 +/- 3 g/L [8.7 +/- 0.3 g/dL]) were maintained constant. During bypass, intracranial pressure progressively increased in the alpha-stat group from 6.0 +/- 1.0 to 13.9 +/- 1.8 mm Hg (p less than 0.05) and in the pH-stat group from 7.7 +/- 1.1 to 14.7 +/- 1.4 mm Hg (p less than 0.05), although there was no evidence of loss of intracranial compliance or intracranial edema formation as assessed by brain water content. With cooling, cerebral blood flow decreased by 56% to 62% in the alpha-stat group (p less than 0.05) and by 48% to 56% in the pH-stat group (p less than 0.05). However, 30 minutes after rewarming to 37 degrees C, cerebral blood flow in both groups failed to increase and remained significantly depressed compared with baseline values. Both groups showed similar amounts of ischemic retinal damage, with degeneration of bipolar cells found in the inner nuclear layer in 67% of animals. We conclude that, independent of the arterial carbon dioxide tension management technique, (1) cerebral perfusion decreased comparably during prolonged hypothermic bypass, (2) intracranial pressure increases progressively, (3) ischemic damage to retinal cells occurs despite maintenance of aortic pressure and flow, and (4) a significant reduction in cerebral perfusion persists after rewarming.     

Use of a pH-stat strategy during retrograde cerebral perfusion improves cerebral perfusion and tissue oxygenation

BACKGROUND: Although it is well documented that the use of a pH-stat strategy during hypothermic cardiopulmonary bypass improves cerebral blood flow, an alpha-stat strategy has been almost exclusively used during retrograde cerebral perfusion. We investigated the effects of pH-stat and alpha-stat management on brain tissue blood flow and oxygenation during retrograde cerebral perfusion in a porcine model to determine if the use of a pH-stat strategy during retrograde cerebral perfusion improves brain tissue perfusion. METHODS: Fourteen pigs were managed by an alpha-stat strategy (alpha-stat group, n = 7) or by a pH-stat strategy (pH-stat group, n = 7) during 120 minutes of hypothermic retrograde cerebral perfusion. Retrograde cerebral perfusion was established through the superior vena cava. Brain tissue blood flow and oxygenation were measured continuously with a laser flowmeter and near infrared spectroscopy, respectively. Brain tissue water content was determined at the end of the experiments. RESULTS: During cooling, brain tissue blood flow was significantly higher with use of the pH-stat strategy than with the alpha-stat strategy (86% +/- 10% versus 40% +/- 3% of baseline). During retrograde cerebral perfusion, brain tissue blood flow was also significantly higher (about three times higher) in the pH-stat group than in the alpha-stat group (15% +/- 4% versus 5% +/- 1% of baseline at 60 minutes of retrograde cerebral perfusion). Tissue oxygen saturation appeared to be higher during retrograde cerebral perfusion in the pH-stat group than in the alpha-stat group. Brain tissue blood flow during rewarming remained significantly higher with the use of pH-stat than with the use of alpha-stat. Brain tissue water contents were similar in both groups. CONCLUSIONS: In our pig model, the use of a pH-stat strategy during retrograde cerebral perfusion significantly improves brain tissue perfusion. Therefore, to improve retrograde cerebral blood flow during retrograde cerebral perfusion, it may be preferable to use a pH-stat strategy, rather than an alpha-stat strategy.     

pH-Stat Management Reduces the Cerebral Metabolic Rate for Oxygen during Profound Hypothermia (17 degrees Celsius): A Study during Cardiopulmonary Bypass in Rabbits

Background: Greater cerebral metabolic suppression may increase the brain's tolerance to ischemia. Previous studies examining the magnitude of metabolic suppression afforded by profound hypothermia suggest that the greater arterial carbon dioxide tension of pH-stat management may increase metabolic suppression when compared with alpha-stat management.

Methods: New Zealand White rabbits, anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary bypass (CPB) at a brain temperature of 17 degrees Celsius with alpha-stat (group A, n = 9) or pH-stat (group B, n = 9) management. Measurements of brain temperature, systemic hemodynamics, arterial and cerebral venous blood gases and oxygen content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95 min of CPB. To control for arterial pressure and CBF differences between techniques, additional rabbits underwent CPB at 17 degrees Celsius. In group C (alpha-stat, n = 8), arterial pressure was decreased with nitroglycerin to values observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure was increased with angiotensin II to values observed with alpha-stat management. In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after (95 min of CPB) arterial pressure manipulation.

Results: In groups A (alpha-stat) and B (pH-stat), arterial pressure; hemispheric CBF (44 plus/minus 17 vs. 21 plus/minus 4 ml *symbol* 100 g sup -1 *symbol* min sup -1 [median plus/minus quartile deviation]; P = 0.017); and CMRO2 (0.54 plus/minus 0.13 vs. 0.32 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.0015) were greater in alpha-stat than in pH-stat animals, respectively. As a result of arterial pressure manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure (75 plus/minus 2 vs. 78 plus/minus 2 mm Hg) nor hemispheric CBF (40 plus/minus 10 vs. 48 plus/minus 6 ml *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.21) differed between alpha-stat and pH-stat management, respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat animals (0.71 plus/minus 0.10 vs. 0.45 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.002).     

Arterial blood gas management in retrograde cerebral perfusion: the importance of carbon dioxide.

OBJECTIVES: Many interventional physiological assessments for retrograde cerebral perfusion (RCP) have been explored. However, the appropriate arterial gas management of carbon dioxide (CO2) remains controversial. The aim of this study is to determine whether alpha-stat or pH-stat could be used for effective brain protection under RCP in terms of cortical cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and distribution of regional cerebral blood flow. METHODS: Fifteen anesthetized dogs (25.1+/-1.1 kg) on cardiopulmonary bypass (CPB) were cooled to 18 degrees C under alpha-stat management and had RCP for 90 min under: (1), alpha-stat; (2), pH-stat; or (3), deep hypothermic (18 degrees C) antegrade CPB (antegrade). RCP flow was regulated for a sagittal sinus pressure of around 25 mmHg. CBF was monitored by a laser tissue flowmeter. Serial analyses of blood gas were made. The regional cerebral blood flow was measured with colored microspheres before discontinuation of RCP. CBF and CMRO2 were evaluated as the percentage of the baseline level (%CBF, %CMRO2). RESULTS: The oxygen content of arterial inflow and oxygen extraction was not significantly different between the RCP groups. The %CBF and %CMRO2 were significantly higher for pH-stat RCP than for alpha-stat RCP. The regional cerebral blood flow, measured with colored microspheres, tended to be higher for pH-stat RCP than for alpha-stat RCP, at every site in the brain. Irrespective of CO2 management, regional differences were not significant among any site in the brain. CONCLUSIONS: CO2 management is crucial for brain protection under deep hypothermic RCP. This study revealed that pH-stat was considered to be better than alpha-stat in terms of CBF and oxygen metabolism in the brain. The regional blood flow distribution was considered to be unchanged irrespective of CO2 management.     

Cerebral vasoreactivity to carbon dioxide during cardiopulmonary perfusion at normothermia and hypothermia

With the pH-stat acid-base regulation strategy during hypothermic cardiopulmonary bypass (CPB), carbon dioxide (CO2) is generally administered to maintain the partial pressure of arterial CO2 at a higher level than with the alpha-stat method. With preserved CO2 vasoreactivity during CPB, this induction of "respiratory acidosis" can lead to a much higher cerebral blood flow level than is motivated metabolically. To evaluate CO2 vasoreactivity, cerebral blood flow was measured using a xenon 133 washout technique before, during, and after CPB at different CO2 levels in patients who were undergoing coronary artery bypass grafting with perfusion at either hypothermia or normothermia. The overall CO2 reactivity was 1.2 mL/100 g/min/mm Hg. There was no difference between the groups. The CO2 reactivity was not affected by temperature or CPB. The induced hemodilution resulted in higher cerebral blood flow levels during CPB, although this was counteracted by the temperature-dependent decrease in the hypothermia group. After CPB, a transient increase in cerebral blood flow was noted in the hypothermia group, the reason for which remains unclear. The study shows that manipulation of the CO2 level at different temperatures results in similar changes in cerebral blood flow irrespective of the estimated metabolic demand. This finding further elucidates the question of whether alpha-stat or pH-stat is the most physiological way to regulate the acid-base balance during hypothermic CPB.     

Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man.

Recent experimental and clinical investigations provide conflicting evidence regarding the effects of changes in the systemic flow rate from the pump oxygenator on cerebral blood flow and the cerebral metabolic rate of oxygen consumption. However, the results of existing clinical studies are difficult to interpret because of the confounding effects of differences in management of arterial carbon dioxide tension and use of anesthetic and vasoactive agents during cardiopulmonary bypass. To clarify the relationship among perfusion flow rate, cerebral blood flow, and cerebral metabolic rate of oxygen consumption in man during hypothermic cardiopulmonary bypass, we varied perfusion flow rate in random order to either 1.75 or 2.25 L.min-1.m-2 and studied cerebral blood flow (measured by clearance of xenon 133) and cerebral metabolic rate of oxygen consumption (estimated as the product of cerebral blood flow and the cerebral arteriovenous oxygen content difference) in patients managed with both the alpha-stat (group 1) and the pH-stat (group 2) methods of pH and arterial carbon dioxide tension adjustment. We measured the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. In each patient other variables known to exert effects on cerebral blood flow and cerebral metabolic rate of oxygen consumption, including temperature, arterial carbon dioxide tension, arterial oxygen tension, mean arterial pressure, and hematocrit, were maintained constant between measurements. In both groups, mean arterial pressure at both pump flow rates was similar because of spontaneous reciprocal alterations in systemic vascular resistance, that is, as perfusion flow rate declined, systemic vascular resistance increased; as perfusion flow rate increased, systemic vascular resistance declined. Under these tightly controlled conditions, pump flow variation per se exerted no effect on cerebral blood flow or cerebral metabolic rate of oxygen consumption in either group.     

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.     

Cerebral hemodynamics in neonates and infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest: assessment by transcranial Doppler sonography

Profound hypothermic circulatory arrest (PHCA) is followed by a transient period of increased intracranial pressure and a longer period of neurophysiologic dysfunction. To investigate the effect of cardiopulmonary bypass (CPB) with PHCA on cerebral hemodynamics, we used transcranial Doppler sonography to measure cerebral blood flow velocity in 10 neonates and infants before and after PHCA. Cerebral blood flow velocity was compared before and after PHCA during normothermic cardiopulmonary bypass at the same mean arterial pressure, central venous pressure, hematocrit, and arterial carbon dioxide tension. Cerebral blood flow velocity decreased exponentially with decreasing nasopharyngeal temperature before PHCA (P less than 0.05) and remained decreased after PHCA during normothermic CPB, compared with values for normothermic CPB before PHCA (P less than 0.005). During normothermic CPB after PHCA, the modified cerebral vascular resistance (mm Hg.cm.s-1) was increased above values for normothermic CPB before PHCA (P less than 0.05). The results of this study suggest that the observed increase in intracranial pressure during PHCA is not caused by increased cerebral perfusion, but rather that cerebral perfusion is reduced in response to a decreased demand for cerebral metabolic oxygen.     

Carbon dioxide management and the cerebral response to hemodilution during hypothermic cardiopulmonary bypass in dogs

BACKGROUND: Increases in blood flow support oxygen (O2) delivery with hemodilution. However, with alpha-stat management, the cerebral response to hemodilution is blunted. We tested the hypothesis that carbon dioxide (CO2) management is a primary determinant of the cerebral blood flow (CBF) response to hemodilution during hypothermic bypass. METHODS: Following Animal Care Committee approval, 15 dogs underwent bypass at 18 degrees C (pH-stat, n = 7 or alpha-stat, n = 8). Measurements were obtained after progressive hemodilution, and cerebral blood flow was determined by sagittal sinus outflow. Arterial pressure was maintained at 60 to 70 mm Hg. The CBF response to hemodilution and cerebral metabolic rate were compared in the two groups of animals. RESULTS: In both groups, hemodilution increased CBF. At every hematocrit, CBF and O2 delivery in the pH-stat group exceeded that of alpha-stat group, although O2 demand did not differ between groups. While absolute CBF in the pH-stat group was greater at every hematocrit, the relative change in CBF from control and the slope of the CBF-Hct relationship did not differ between groups. CONCLUSIONS: pH-stat management is associated with a greater absolute CBF and a greater ratio of cerebral O2 supply to demand for any degree of hemodilution. However, over the range of hematocrits common in practice, CO2 management per se does not determine the cerebral response to hemodilution.     

Autoregulation and the CO2 responsiveness of cerebral blood flow after cardiopulmonary bypass

Cerebral blood flow (CBF) was measured by 133Xe clearance to determine whether there were any residual effects of cardiopulmonary bypass (CPB) on the CBF response to changes in arterial PCO2 or blood pressure in the early (3-8 hr) post-CPB period. During CPB, the nine patients studied were managed according to alpha-stat, temperature uncorrected, pH management. The mean +/- SD increase in CBF resulting from an increase in PaCO2 (1.35 +/- 0.5 ml.100 g-1.min-1.mmHg-1 PaCO2) was within the normal range, indicating appropriate CBF response to a change in PaCO2. There were no significant differences in CBF, being 25.7 ml.100 g-1.min-1 at a mean arterial blood pressure of 70 mmHg and 26.5 ml.100 g-1.min-1 at 110 mmHg, demonstrating intact cerebral autoregulation over this pressure range. We conclude that cerebral autoregulation and CO2 responsiveness are preserved in the immediate postoperative period after CPB using alpha-stat pH management.     

Optimal pH strategy for selective cerebral perfusion.

OBJECTIVE: Selective cerebral perfusion (SCP) affords brain protection superior to hypothermic circulatory arrest (HCA) for prolonged aortic arch procedures. Optimal pH strategy for HCA is controversial; for SCP it is unknown. We compared pH strategies during SCP in a survival pig model. METHODS: Twenty juvenile pigs (26+/-2.4 kg), randomized to alpha-stat (n=10) or pH-stat (n=10) management, underwent cooling to 20 degrees C on cardiopulmonary bypass (CPB) followed by 90 min of SCP at 20 degrees C. SCP was conducted with a mean pressure of 50 mmHg and hematocrit of 22.5%. Using fluorescent microspheres and sagittal sinus blood sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at the following time points: baseline, after 30 min cooling (20 degrees C), 30 min of SCP, 90 min of SCP, 15 min post-CPB and 2h post-CPB. Visual evoked potentials (VEP) were assessed at baseline and monitored for 2h during recovery. Neurobehavioral recovery (10=normal) was assessed in a blinded fashion for 7 postoperative days. RESULTS: There were no significant differences between the groups at baseline. CBF was significantly higher at the end of cooling, and after 30 and 90 min of SCP in the pH-stat group (P=0.02, 0.007, 0.03). CMRO2 was also higher with pH-stat (P=0.06, 0.04, 0.10). Both groups showed prompt return to values close to baseline after rewarming (P=ns). VEP suggested a trend towards improved recovery in the alpha-stat group at 2h post-CPB, P=0.15. However, there were no significant differences in neurobehavioral score: (alpha-stat versus pH-stat) median values 7 and 7.5 on day 1; 9 and 9 on day 4, and 10 and 10 on day 7. CONCLUSIONS: These data suggest that alpha-stat management for SCP provides more effective metabolic suppression than pH-stat, with lower CBF. Clinically, the better preservation of cerebral autoregulation during alpha-stat perfusion should reduce the risk of embolization.     

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.     

Hemodynamics and metabolism during surface-induced hypothermia in the dog: a comparison of pH management strategies

The management of blood pH during hypothermia remains controversial. The present study was designed to determine whether hemodynamics and oxygen consumption during hypothermia are different between the alpha-stat and pH-stat strategies. Theoretical considerations of enzyme kinetics suggest that the alpha-stat strategy would result in a higher oxygen consumption during hypothermia. Because hypothermia is used to decrease oxygen consumption for protection during ischemia, a pH scheme that results in a greater oxygen demand for any level of ischemia would be detrimental. The core temperature of 22 dogs was lowered to 26 degrees C by combined surface cooling and gastric irrigation. Either the alpha-stat (N = 9) or the pH-stat (N = 13) pH strategy was used. The arterial pressure was different between the two groups at 26 degrees C (65 +/- 6 vs 85 +/- 6 mm Hg, alpha-stat vs pH-stat, respectively, P less than 0.05). Neither systemic oxygen consumption nor the Q10 was different between groups. There were no differences in any other hemodynamic parameters. In summary, during moderate hypothermia alpha-stat pH management results in an arterial pressure lower than that of pH-stat management, possibly resulting in improved peripheral perfusion. Despite theoretical predictions, the alpha-stat pH scheme does not result in an oxygen consumption higher than that of the pH-stat scheme.     

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.     

Brain blood flow and metabolism do not decrease at stable brain temperature during cardiopulmonary bypass in rabbits.

Cerebral blood flow (CBF) during human hypothermic cardiopulmonary bypass has been reported to decrease with time, suggesting that progressive cerebral vasoconstriction or embolic obstruction may occur. We tested the hypotheses: 1) that observed CBF reductions were due to continued undetected brain cooling and 2) that CBF during cardiopulmonary bypass would be stable after achievement of constant brain temperature. Anesthetized New Zealand White rabbits underwent cardiopulmonary bypass (membrane oxygenator, centrifugal pump, bifemoral arterial perfusion) and were assigned to one of three bypass management groups based on perfusate temperature and PaCO2 management: group 1 (37 degrees C, n = 8); group 2 (27 degrees C, pH-stat, n = 9); and group 3 (27 degrees C, alpha-stat, n = 8). Systemic hemodynamics, and cerebral cortical, esophageal, and arterial perfusate temperatures were recorded every 10 min for the first hour of bypass and again at 90 min. CBF and masseter blood flow (radiolabeled microspheres) were determined at 30, 60, and 90 min of bypass, while the cerebral metabolic rate for oxygen (CMRO2) was determined at 60 and 90 min. Groups were comparable with respect to mean arterial pressure, central venous pressure, hematocrit, and arterial oxygen content throughout bypass. Cortical temperature was stable in normothermic (group 1) animals, and there was no significant change in CBF between 30 and 90 min of bypass: 68 +/- 18 versus 73 +/- 20 ml.100 g-1.min-1 (mean +/- SD). In the hypothermic groups (2 and 3), cortical temperature equilibration (95% of the total change) required 41 +/- 6 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of alpha-stat vs. pH-stat strategies on cerebral oximetry during moderate hypothermic cardiopulmonary bypass

BACKGROUND AND OBJECTIVES: This study was undertaken to compare the effect of alpha-stat vs. pH-stat strategies for acid-base management on regional cerebral oxygen saturation (RsO2) in patients undergoing moderate hypothermic haemodilution cardiopulmonary bypass (CPB). METHODS: In 14 adult patients undergoing elective coronary artery bypass grafting, an awake RsO2 baseline value was monitored using a cerebral oximeter (INVOS 5100). Cerebral oximetry was then monitored continuously following anaesthesia and during the whole period of CPB. Mean +/- SD of RsO2, CO2, mean arterial pressure and haematocrit were determined before bypass and during the moderate hypothermic phase of the CPB using the alpha-stat followed by pH-stat strategies of acid-base management. Alpha-stat was then maintained throughout the whole period of CPB. RESULTS: The mean baseline RsO2 in the awake patient breathing room air was 59.6 +/- 5.3%. Following anaesthesia and ventilation with 100% oxygen, RsO2 increased up to 75.9 +/- 6.7%. Going on bypass, RsO2 significantly decreased from a pre-bypass value of 75.9 +/- 6.7% to 62.9 +/- 6.3% during the initial phase of alpha-stat strategy. Shifting to pH-stat strategy resulted in a significant increase of RsO2 from 62.9 +/- 6.3% to 72.1 +/- 6.6%. Resuming the alpha-stat strategy resulted in a significant decrease of RsO2 to 62.9 +/- 7.8% which was similar to the RsO2 value during the initial phase of alpha-stat. CONCLUSION: During moderate hypothermic haemodilutional CPB, the RsO2 was significantly higher during the pH-stat than during the alpha-stat strategy. However, the RsO2 during pH-stat management was significantly higher than the baseline RsO2 value in the awake patient breathing room air, denoting luxury cerebral perfusion. In contrast, the RsO2 during alpha-stat was only slightly higher than the baseline RsO2, suggesting that the alpha-stat strategy avoids luxury perfusion, but can maintain adequate cerebral oxygen supply-demand balance during moderate hypothermic haemodilutional CPB.     

Bypass flow, mean arterial pressure, and cerebral perfusion during cardiopulmonary bypass in dogs

OBJECTIVE: To determine if normal cardiopulmonary bypass (CPB) pump flows maintain cerebral perfusion in the context of reduced mean arterial pressure at 33 degrees C. DESIGN: A prospective investigation. SETTING: Animal CPB research laboratory. PARTICIPANTS: Seven dogs that underwent CPB. INTERVENTIONS: Seven dogs underwent CPB at 33 degrees C using alpha-stat management and a halothane, fentanyl-midazolam anesthetic. Cerebral blood flow was measured using the sagittal sinus outflow technique. After control measurements at 70 mm Hg, cerebral physiologic values were determined under four conditions in random order: (1) mean arterial pressure of 60 mm Hg achieved by a reduction in pump flow, (2) mean arterial pressure of 60 mmHg determined by partial opening of a femoral arterial-to-venous reservoir shunt, (3) mean arterial pressure of 45 mm Hg by reduced pump flow, and (4) mean arterial pressure of 45 mm Hg by shunt. A 9F femoral arterial-to-venous reservoir shunt was controlled by a screw clamp. MEASUREMENTS AND MAIN RESULTS: Except for the controlled variables of mean arterial pressure and bypass flow, physiologic determinants of cerebral blood flow (temperature, PaCO2 and hematocrit) did not differ under any of the CPB conditions. Pump flow per se was not a determinant of cerebral perfusion. Cerebral blood flow and cerebral oxygen delivery did not differ with changes in pump flow if mean arterial pressure did not differ. Cerebral blood flow depended on mean arterial pressure under all pump flow conditions, however. CONCLUSIONS: Over the range of flows typical in adult CPB at 33 degrees C, pump flow does not have an effect on cerebral perfusion independent of its effect on mean arterial pressure. A targeted pump flow per se is not sufficient to maintain cerebral perfusion if mean arterial blood pressure is reduced.     

Comparative analysis of alpha-stat and pH-stat strategies with a membrane oxygenator during deep hypothermic circulatory arrest in young pigs

Using young pigs, this study compared the strategies of alpha-stat and pH-stat during deep hypothermic circulatory arrest (DHCA) for the cooling time of brains during the induction of hypothermia and rewarming time with cardiopulmonary bypass (CPB); the cerebral perfusion rate and metabolism rate, and the ratio of these 2 rates; and the extent of the cerebral edema development after circulatory arrest. Fourteen young pigs were assigned to 1 of 2 strategies of gas management. Cerebral blood flow was measured with a cerebral venous outflow technique. With CPB, core cooling was initiated and continued until the nasopharyngeal temperature fell below 20 degrees C. The flow rate was set at 2,500 ml/min. Once the temperature reached below 20 degrees C, the animals were subjected to DHCA for 40 min. During the cooling period, the acid-base balance was maintained using either alpha-stat or pH-stat strategy. After DHCA, the body was rewarmed to the normal body temperature. The animals then were sacrificed, and we measured the brain water content. The cerebral perfusion and metabolism rates were measured before the onset of CPB, before cooling, before DHCA, 15 min after rewarming, and upon the completion of rewarming. The cooling time was significantly shorter with alpha-stat than with pH-stat strategy while no significant differences were observed in the rewarming time between groups. Also, no significant differences were found in cerebral blood flow volume, metabolic rate, or flow/metabolic rate ratio between groups. In each group, the cerebral blood flow volume, metabolic rate, and flow/metabolic rate ratio showed significant differences in body temperature. Brain water content showed no significant differences between the 2 groups. In summary, this study found no significant differences between alpha-stat and pH-stat strategies, except in the cooling time. The cooling time was rather shorter with the alpha-stat than with the pH-stat strategy.