Effect of alpha-stat versus pH-stat strategy on oxyhemoglobin dissociation and whole-body oxygen consumption during hypothermic cardiopulmonary bypass.

To determine whether alpha-stat or pH-stat strategy should be used, 20 patients undergoing coronary artery bypass grafting during moderate hypothermic hemodilutional cardiopulmonary bypass were studied. The carbon dioxide management during bypass was randomly done according to alpha-stat strategy in 10 patients (i.e., temperature-uncorrected PaCO2 was kept near 40 mm Hg and uncorrected pHa was kept at about 7.4) and according to pH-stat strategy in the other 10 patients (i.e., temperature-corrected PaCO2 was kept near 40 mm Hg and uncorrected pHa was kept at about 7.4). In both groups, when the central venous temperature was stable at 26.5 +/- 2.5 degrees C, the perfusion flow was altered sequentially from 2.4 to 1.8 and 1.2 L.min-1.m-2. The mixed venous oxyhemoglobin saturation at the different perfusion flows was monitored by the Oxy-Stat meter and was correlated with the corresponding mixed venous oxygen tension to construct an oxyhemoglobin dissociation curve. Also, the whole-body oxygen consumption at the different perfusion flows was computed. The whole-body oxygen consumption and the oxyhemoglobin dissociation were not significantly different between the alpha-stat and the pH-stat groups. In both groups, the dissociation curve is shifted to the left, but the oxygen consumption per unit time does not significantly change despite decreasing the perfusion flow from 2.4 to 1.2 L.min-1.m-2. The results suggest that oxygen delivery is not impaired during moderate hypothermic cardiopulmonary bypass independent of whether alpha-stat or pH-stat strategy is used.     

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.     

Influence of pH management on hemodynamics and metabolism in moderate hypothermia.

In moderate hypothermia, three different concepts of pH management have been described to date: pH-stat, alpha-stat, and alkalinity. In our study these pH strategies were compared in adult sheep, with animals serving as their own controls for direct comparability. Hemodynamic parameters, such as mean aortic pressure (from 109 +/- 12 to 72 +/- 23 mm Hg), cardiac output (from 5.55 +/- 1.25 to 4.5 +/- 0.82 L/min), and systemic oxygen consumption (from 3.73 +/- 0.8 to 1.81 +/- 0.4 ml/kg/min), decreased significantly with alpha-stat at 28 degrees C from values for normothermia. No marked or even significant differences were found among the three pH strategies in any value, with the exception of body oxygen consumption. The difference of 2% between pH-stat and alpha-stat, at 0.06 ml oxygen/kg/min, was significant (p < or = 0.05), however of no practical relevance because hypothermia itself caused a decrease of nearly 52%. With regard to myocardial parameters, pH-stat impaired myocardial function compared with both alpha-stat and alkalinity. At nearly identical mean aortic pressures and cardiac outputs, myocardial oxygen consumption reached the highest level in pH-stat (7.65 ml oxygen/100 gm/min; alpha-stat, 6.76 ml oxygen/100 gm/min; p < or = 0.05). Myocardial efficiency thus decreased from 21% (alpha-stat) to 17% (pH-stat). No evident changes in hemodynamic and metabolic values were found for alkalinity vs alpha-stat. The best response to continuously infused epinephrine, however, was found with alkalinity. According to our data there was an impairment of myocardial function without any evident further reduction in body metabolism with pH-stat vs alpha-stat. There were, however, no marked metabolic or hemodynamic differences between alkalinity and alpha-stat, with the exception of a better preservation of sensitivity to adrenergic stimuli with alkalinity.     

The effect of acid-base management on the oxygen uptake of the human body during hypothermic extracorporeal circulation]

The effects of two different systems of acid-base management on whole-body oxygen consumption during and following hypothermic cardiopulmonary bypass were investigated in 42 patients undergoing coronary artery bypass grafting or valve replacement surgery. In group I (22 patients) pH-stat management and in group II (20 patients) alpha-stat management was used. METHODS. Anesthesia was performed with fentanyl, midazolam, and pancuronium bromide. Halothane was added whenever MAP exceeded 100 mmHg. Cardiopulmonary bypass was conducted with a membrane oxygenator and a roller pump. Pump flow varied between 2 and 2.5 l/min per m2 body surface area. Once patients had been initially cooled down to a venous blood temperature of 27 degrees C they were kept stable between 28 degrees C and 30 degrees C during the ischemic phase. Measurements were performed after sternotomy during normothermia (control values) and every 15 min from the start until termination of bypass. RESULTS AND DISCUSSION. Neither hemodynamic parameters (MAP, CI, SVR) nor rectal or skin temperatures differed significantly between the two groups during the entire study period. Although at 27 degrees C oxygen availability fell by 43% and 35% in groups I and II, respectively, mixed venous oxygen saturation was significantly elevated compared with the control value, because of a decrease of 60% and 51%, respectively, in the arterio-venous oxygen content difference and of 62% and 55%, respectively, in oxygen consumption. Rewarming led to normalization of the metabolic parameters except for oxygen availability, which was still decreased as a result of low hemoglobin content. After termination of the bypass oxygen consumption increased steadily, which may have been due either to the beginning of shivering or to repayment of an oxygen debt caused by hypothermic bypass. As statistically significant differences were detected between the two groups in metabolic parameters during the course of the investigation, the hypothesis of Rahn and Reeves [2, 3], according to which oxygen consumption must be expected to be higher with alpha-stat than with pH-stat management, could not be verified by this study.     

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.     

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.     

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).     

Effect of differing acid-base regulation on cerebral blood flow autoregulation during cardiopulmonary bypass.

Cerebral dysfunction following cardiopulmonary bypass may be aggravated by altered autoregulation of cerebral blood flow. We have used trans-cranial Doppler to measure middle cerebral artery blood flow velocity during cardiopulmonary bypass managed by either pH-stat or alpha-stat acid-base protocols. Fourteen patients were studied, 7 in each group. During bypass at 28 degrees C, patients underwent incremental alterations in mean arterial pressure from 20-90 mmHg, maintaining systemic perfusion flow at 1.75 L/min per m2. The cerebral extraction ratio of oxygen was measured to indicate matching of cerebral blood flow to demand. The pH-stat group showed a pressure passive cerebral circulation with significant (r = 0.999, P less than 0.05) increase in blood flow velocity with increasing arterial pressure. This also occurred in alpha-stat group during the pressure range of 20-50 mmHg (r = 0.951, P less than 0.05). During the pressure range of 50-90 mmHg in alpha-stat group the change in flow velocity (0.16 cm/sec per mmHg) was significantly (P less than 0.05) less than that in pH-stat group (0.58 cm/second per mmHg). The cerebral extraction ratio of oxygen was less depressed in the alpha-stat group than in the pH-stat group, indicating more appropriate matching of cerebral blood flow and tissue demand. These results suggest that, during alpha-stat managed cardiopulmonary bypass, cerebral blood flow velocity is less subject to wide pressure alteration than pH-stat.     

Optimal pH and PaCO2 during moderate hypothermia]

Effects of pH and PaCO2 on cerebral as well as systemic hemodynamics and oxygen consumption were investigated during moderate hypothermia under 0.5% halothane anesthesia. Twenty-seven adult mongrel dogs were cooled to 28 degrees C (brain temperature) with a surface cooling method. They were divided into 3 groups, pH-stat (pH 7.35 n = 9), alpha-stat (pH 7.48 n = 9), and alkalosis (pH 7.70 n = 9). During hypothermia cardiac index fell to 74%, 56%, and 45%, and cerebral blood flow to 54%, 42%, and 36% in pH-stat, alpha-stat and alkalosis groups, respectively. Cerebral and systemic oxygen consumptions decreased to approximately 54% and 47%, respectively in all groups. Cerebrospinal fluid pH rose from 7.36 precooling to 7.49 (pH-stat), 7.53 (alpha-stat), and 7.72 (alkalosis). We concluded from these results that pH-stat and alpha-stat management have no significant effect on either hemodynamics or metabolism during moderate hypothermia but alkalosis management has deleterious effects because of the alkalinity itself and of the hyperventilation by which the alkalosis is induced.     

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.     

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)     

Comparison of pH-stat versus Alpha-stat during hypothermic cardiopulmonary bypass in the prevention and control of acidosis in cardiac surgery

OBJECTIVES: To compare the effects of blood-gas management using either alpha-stat (temperature-uncorrected blood-gas management) or pH-stat (temperature-corrected blood-gas management) strategies, 30 patients undergoing coronary artery bypass surgery allocated randomly to either one of the approaches were studied. Acid-base balance, tissue oxygenation, and biochemical parameters were measured at distinct times: before bypass, after 15 min of hypothermia at 32 degrees C, after 45 min of hypothermia at 32 degrees C, after 15 min of rewarming at 37 degrees C, and 45 min after the end of bypass in normothermic conditions. RESULTS: The groups were similar with regard to physical characteristics, physiological parameters, and bypass time. In the pH-stat group, CO2 administered with the aim of correcting pH for the patients hypothermic temperature caused a significant increase in temperature-uncorrected PaCO2 and a decrease in arterial temperature-uncorrected pH at 45 min. During the rewarming period and following bypass, the pH was lower and PaCO2 higher in the pH-stat group (P < 0.001). CONCLUSION: It was found that during the rewarming period and following bypass, the resulting acidosis caused by the procedure was less in the alpha-stat group. It was found that there were no difference between the two groups, with regard to tissue perfusion, as is seen by the tissue oxygenation parameters and lactic acid concentration.     

Changes in serum S100beta protein and Mini-Mental State Examination after cold (28 degrees C) and warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat)

BACKGROUND: The effect of cardiopulmonary bypass temperature and blood gas management on the brain is still controversial. This study was designed to compare the changes in S100beta protein concentration and Mini-Mental State Examination in patients undergoing cold (28 degrees C) vs. warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat). METHODS: Sixty patients were randomly allocated to one of four equal groups (cold alpha-stat, cold pH-stat, warm alpha-stat, warm pH-stat). Serum S100beta concentrations were measured before CPB, directly after CPB, at 4.5 h and at 24 h after CPB. Mini-Mental State Examination was performed one day before surgery and on day five after the operation. Antegrade warm blood cardioplegia (37 degrees C) was used in all patients. RESULTS: There was no significant difference in postoperative S100beta protein levels between the four groups. Also, there was no interaction between bypass temperature and type of blood gas strategy on S100beta levels after bypass (directly after bypass, 4.5 h and 24 h after bypass). Mini-Mental State Examination score was not affected by blood gas strategy but it was significantly lower in patients undergoing cold cardiopulmonary bypass surgery: median (range), 26 (12-29) vs. 27 (23-30) in warm patients, P = 0.014. There was no significant correlation between Mini-Mental State Examination score 5 days after CPB and S100beta levels at any of the studied time-points after CPB. CONCLUSION: These results support the use of warm CPB (34 degrees C) in patients undergoing coronary artery bypass surgery regardless of the type of blood gas strategy.     

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.     

The effect of temperature on cerebral metabolism and blood flow in adults during cardiopulmonary bypass.

The effect of temperature on cerebral blood flow and metabolism was studied in 41 adult patients scheduled for operations requiring cardiopulmonary bypass. Plasma levels of midazolam and fentanyl were kept constant by a pharmacokinetic model-driven infusion system. Cerebral blood flow was measured by xenon 133 clearance (initial slope index) methods. Cerebral blood flow determinations were made at 27 degrees C (hypothermia) and 37 degrees C (normothermia) at constant cardiopulmonary bypass pump flows of 2 L/min/m2. Blood gas management was conducted to maintain arterial carbon dioxide tension (not corrected for temperature) 35 to 40 mm Hg and arterial oxygen tension of 150 to 250 mm Hg. Blood gas samples were taken from the radial artery and the jugular bulb. With decreased temperature there was a significant (p less than 0.0001) decrease in the arterial venous-oxygen content difference, suggesting brain flow in excess of metabolic need. For each patient, the cerebral metabolic rate of oxygen consumption at 37 degrees C and 27 degrees C was calculated from the two measured points at normothermia and hypothermia with the use of a linear relationship between the logarithm of cerebral metabolic rate of oxygen consumption and temperature. The temperature coefficient was then computed as the ratio of cerebral metabolic rate of oxygen consumption at 37 degrees C to that at 27 degrees C. The median temperature coefficient for man on nonpulsatile cardiopulmonary bypass is 2.8. Thus reducing the temperature from 37 degrees to 27 degrees C reduces cerebral metabolic rate of oxygen consumption by 64%.     

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)     

Early effects of acid-base management during hypothermia on cerebral infarct volume,edema, and cerebral blood flow in acute focal cerebral ischemia in rats

BACKGROUND: Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and alpha-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats. METHODS: Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33 degrees C). Animals were artificially ventilated with either alpha- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[(14)C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS). RESULTS: Compared with the alpha-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm(3) vs. 53.6 +/- 21.6 mm(3); P > or = 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0% vs. 3.1 +/- 2.4%; P > or = 0.05). Global CBF during pH-stat management exceeded that of alpha-stat animals (69.5 +/- 12.3 ml x 100 g(-1) x min(-1) vs. 54.7 +/- 13.3 ml x 100 g(-1) x min; P > or = 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml x 100 g(-1) x min(-1) in the pH-stat group versus 48.2 +/- 7.2 ml x 100 g(-1) x min(-1) in the alpha-stat group ( P> or = 0.05). CONCLUSIONS: In the very early reperfusion period (5 h), pH-stat management significantly decreases cerebral infarct volume and edema as compared with alpha-stat during moderate hypothermia, probably by increasing CBF.     

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.     

Transcranial Doppler-estimated versus thermodilution-estimated cerebral blood flow during cardiac operations. Influence of temperature and arterial carbon dioxide tension

The ability of the noninvasive continuous transcranial Doppler technique to reflect changes in cerebral blood flow during cardiac operations was evaluated in seven adults. Middle cerebral artery blood flow velocity changes were compared with simultaneous thermodilution measurements of venous blood flow in the ipsilateral internal jugular vein during 11 preset stages of the procedure. Cerebral blood flow was varied by changes in arterial carbon dioxide tension and temperature. High-dose fentanyl-droperidol anesthesia and alpha-stat pH management were employed. To facilitate comparisons between the two methods, the individual awake values of middle cerebral artery flow velocity (45.1 +/- 3.3 cm/sec, mean +/- standard error of the mean) and jugular venous blood flow (382 +/- 37 ml/min) were normalized (100%). Cerebral metabolic rate for oxygen was calculated as the product of jugular arteriovenous oxygen content difference and middle cerebral artery flow velocity or jugular venous blood flow, respectively. The individual correlations between the two flow estimates varied between 0.76 and 0.87 (median 0.83), and the correlation of the combined data from all seven patients was 0.77 (p less than 0.0001). Variations in arterial carbon dioxide tension induced significant changes in the two flow estimates both during normothermia before cardiopulmonary bypass and at deep hypothermia (20 degrees C) during cardiopulmonary bypass. The significant arterial carbon dioxide tension changes had no significant effects either on Doppler- or thermodilution-estimated cerebral metabolic rate for oxygen. Deep hypothermia (20 degrees C) reduced Doppler- and thermodilution-estimated cerebral metabolic rate for oxygen to 22.0% +/- 3.9% and 20.6% +/- 6.9% of the awake levels, respectively. The study supports the validity of using middle cerebral arterial flow velocity changes as an estimate of changes in volume flow through the brain during cardiac operations.     

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.