Changes in cerebral oxygenation during cold (28 degrees C) and warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat) in patients undergoing coronary artery bypass graft surgery

BACKGROUND: Impaired cerebral oxygenation, which is reflected by measuring jugular bulb oxygenation, is thought to play an important role in the development of neurological injury after cardiac operations with cardiopulmonary bypass (CPB). The effects of cardiopulmonary temperature and blood gas strategy on cerebral oxygenation are not fully appreciated. METHODS: Sixty patients were randomly allocated into four equal groups (cold alpha-stat, cold pH-stat, warm alpha-stat and warm pH-stat) to compare the effect of these perfusion strategies on cerebral oxygenation monitored by jugular bulb oximetry [jugular bulb oxygen saturation (SjO(2)) and arterial-jugular bulb oxygen content difference (AjDO(2))]. Jugular bulb oxygen saturation and AjDO(2) were measured before CPB, after 5, 20, 40 min on CPB, at start and end of rewarming, 5 min before the end of CPB and 10 min after CPB. Two-way analysis of variance was used to model the lowest SjO(2) and highest AjDO(2) during CPB, with CPB temperature and blood gas management as contributing factors. RESULTS: Significant changes in SjO(2) were only related to the type of blood gas management, with no significant difference between warm and cold CPB patients. In addition, during rewarming, desaturation (SjO(2) 相似文献   

A pilot study of evaluation of cerebral function by S100beta protein and near-infrared spectroscopy during cold and warm cardiopulmonary bypass in infants and children undergoing open-heart surgery

Cerebral injury in children undergoing cardiopulmonary bypass (CPB) remains a major source of morbidity. The effect of cardiopulmonary bypass temperature on cerebral function in terms of serum S100beta protein level and cerebral oxygenation monitored by near infrared spectroscopy (NIRO-300) in children is not known. In this study, 18 children undergoing open-heart surgery at the Hospital for Sick Children in London were equally assigned by minimisation to warm (35 +/- 1 degrees C) or cold (25 +/- 1 degrees C) CPB. Changes in S100beta protein and cerebral oxygenation were studied in both groups. S100beta protein serum level increased significantly after CPB in both groups. There was no significant difference in serum S100beta protein concentrations between the two groups. However, cerebral oxygenation in terms of tissue oxygen index (TOI) was significantly impaired during rewarming from cold CPB. Five patients were desaturated (TOI < 50%) during rewarming in the cold bypass group compared to two in the warm patients. This study supports the use of warm CPB in children undergoing open-heart surgery, although further studies recruiting more patients are warranted.     

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).     

Differences in pH management and pulsatile/nonpulsatile perfusion during cardiopulmonary bypass do not influence renal function.

The renal effects of pulsatile (pulse pressure 18.0 +/- 1.5 mm Hg [mean +/- SEM]) or nonpulsatile perfusion (mean pulse pressure 1.9 +/- 0.4 mm Hg) during either alpha-stat (mean PaCO2 41.2 +/- 0.9 mm Hg measured at 37 degrees C) or pH-stat (mean PaCO2 60.6 +/- 1.7 mm Hg measured at 37 degrees C) pH management of hypothermic cardiopulmonary bypass (CPB) were studied in 100 patients undergoing elective coronary artery bypass surgery. Mean urine output, fractional excretion of sodium and potassium, and renal failure index all increased during the study period; however, there was no difference among the four different CPB management groups. Mean postoperative creatinine and blood urea nitrogen values decreased compared with preoperative values, again without differences among treatment groups. Three patients developed acute renal insufficiency; of these, two had received nonpulsatile perfusion and pH-stat management, and the other had been managed with pulsatile perfusion and pH-stat management. These three patients all had undergone prolonged CPB and required at least two vasoactive drugs and the use of an intraaortic balloon pump to be weaned from CPB. In patients with normal preoperative renal function undergoing hypothermic CPB, neither the mode of perfusion, pulsatile or nonpulsatile, nor the method of pH management, pH-stat or alpha-stat, influences perioperative renal function.     

Early release pattern of S100 protein as a marker of brain damage after warm cardiopulmonary bypass

Warm blood cardioplegia may be more beneficial to the heart than cold cardioplegia, but the effects of warm cardiopulmonary bypass and warm blood cardioplegia on the brain are controversial. S100 protein is an early marker of brain damage and has been detected after cold cardiopulmonary bypass. We studied S100 concentrations in 20 patients undergoing coronary artery bypass surgery before and after warm cardiopulmonary bypass (34-37 degrees C) using warm blood cardioplegia (37 degrees C) for all patients. The peak level of S100 protein occurred immediately after warm cardiopulmonary bypass, then decreased progressively until the last measurement at 4.5 h after bypass. The peak level appears to be dependent upon the age of the patient, with the following regression equation: y = -3.2 + 0.08x, where y is S100 protein concentration in microg.l-1 and x is patient age in years. Further studies are needed to investigate the clinical significance of this early release pattern. Patient age should be taken into account when studying S100 protein levels after 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%).     

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.     

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.     

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.     

Changes in jugular bulb oxygenation in patients undergoing warm coronary artery bypass surgery (34-37 degrees C)

BACKGROUND AND OBJECTIVE: Imbalance between cerebral oxygen supply and demand is thought to play an important role in the development of cerebral injury during cardiac surgery with cardiopulmonary bypass. METHODS: We studied jugular bulb oxygen saturation, jugular bulb oxygen tension, arterial-jugular bulb oxygen content difference and oxygen extraction ratio in 20 patients undergoing warm coronary artery bypass surgery (34-37 degrees C) with pH-stat blood gas management. RESULTS: Only two patients showed desaturation (jugular bulb oxygen saturation < 50%) at 5 min on bypass, and none from 20 min onwards. Multiple regression models were performed after using bypass temperature, mean arterial pressure, cerebral perfusion pressure, haemoglobin concentration and arterial carbon dioxide tension as independent variables, and arterial-jugular bulb oxygen content difference, jugular bulb oxygen saturation, oxygen extraction ratio and jugular bulb oxygen tension as individual dependent variables. CONCLUSIONS: We found that jugular bulb oxygen saturation, jugular bulb oxygen tension and oxygen extraction ratio are mainly dependent on arterial carbon dioxide tension, and arterial-jugular bulb oxygen content difference is dependent on arterial carbon dioxide tension and the bypass temperature. Our results suggest jugular bulb oxygenation is mainly dependent on arterial carbon dioxide tension during warm cardiopulmonary bypass.     

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.     

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.     

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.     

Effect of acid-base management with or without carbon dioxide on plasma phosphate concentration during and after hypothermic cardiopulmonary bypass.

Variations of the phosphate concentration in plasma were studied in two groups of 12 patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass (CPB). Management of the acid-base status differed between the groups, according to whether or not carbon dioxide was added to the anesthetic gas mixture during hypothermia ('pH-stat' vs. 'alpha-stat' mode) following correction vs. no correction of pCO2 and pH for body temperature. Phosphate variations throughout the study were mostly within normal limits. From the start to the end of CPB, the mean rise in phosphate levels was 70% in the pH-stat group and 37% in the alpha-stat group (p < 0.001). During 3 hours after CPB, the phosphate values continued to rise by a mean of 25% in the alpha-stat patients, but fell by a mean of 3% in the pH-stat patients (p < 0.001). Such different phosphate patterns during and immediately after CPB may reflect profound metabolic disturbances and may be related to the altering effects of CO2 addition and respiratory acidosis on intracellular metabolic activity and phosphate homeostasis.     

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.     

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.     

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.     

Oxygenation within the first 120 h following coronary artery bypass grafting. Influence of systemic hypothermia (32 degrees C) or normothermia (36 degrees C) during the cardiopulmonary bypass: a randomized clinical trial

BACKGROUND: Lung function is often impaired after cardiac surgery performed under cardiopulmonary bypass (CPB). Normothermic CPB has become more common, but it remains unknown whether it reduces post-operative lung function compared with hypothermic CPB. The aim of this study was to investigate oxygenation within the first 120 h after systemic hypothermia and normothermia under CPB. METHODS: Thirty patients undergoing coronary artery bypass grafting (CABG) were randomized to either hypothermic (32 degrees C) or normothermic (36 degrees C) CPB. Oxygenation was studied by a simple method for the estimation of intrapulmonary shunt and ventilation-perfusion (V/Q) mismatch pre-operatively and 4, 48 and 120 h post-operatively by changing Fio2 in four to six steps. V/Q mismatch was described with DeltaPo2 (normal values, 0-2.38 kPa). RESULTS: Shunt and V/Q mismatch (DeltaPo2) increased post-operatively in both groups (P<0.01), with no differences between the groups, and with the nadir values 48 h after surgery, i.e. shunt of 15% (5.8-25%) and DeltaPo2 of 3.0 kPa (0.8-14 kPa) [values given as median (range)]. CONCLUSIONS: Impaired oxygenation is prevalent and prolonged following CABG, with equal intensity after hypothermic and normothermic CPB.     

Normothermic versus hypothermic cardiopulmonary bypass during repair of congenital heart disease.

OBJECTIVE: To compare normothermic cardiopulmonary bypass (CPB) versus hypothermic CPB in pediatric patients undergoing repair of congenital heart disease with focus on biochemical markers for brain damage. DESIGN: Prospective randomized interventional study. SETTING: Postgraduate teaching hospital. PARTICIPANTS: Twenty patients undergoing repair of congenital heart disease. INTERVENTIONS: Patients were randomized to normothermic (36 degrees C) versus hypothermic (25 degrees C) CPB. Serum levels of neuron-specific enolase (NSE) and S-100beta protein were measured in all patients before surgery, immediately after CPB, and 12 and 24 hours after surgery. Blood loss and time for extubation of the trachea were recorded. MEASUREMENTS AND MAIN RESULTS: Before operation, the S-100beta protein and NSE levels were similar in the 2 groups. The S-100beta protein serum level increased significantly after CPB in both groups, whereas no change was found in the NSE level. There was no difference in the change of NSE and S-100beta protein levels between normothermic and hypothermic CPB. Blood loss was significantly less after hypothermic CPB (25 mL/kg/24 h v 42 mL/kg/24 h). Time for extubation was similar. CONCLUSION: No difference was found in the release of brain-specific proteins between normothermic and hypothermic CPB, but blood loss was higher after normothermic CPB.     

Importance of acid-base strategy in reducing myocardial and whole body oxygen consumption during perfusion hypothermia

During induced hypothermia with cardiopulmonary bypass, acid-base management usually follows one of two strategies: the so-called ectothermic or alpha-stat strategy, in which the pH of the arterial blood increases 0.015 pH units for every degree Celsius decrease in body temperature, or the pH-stat strategy, in which pH remains 7.4 at all temperatures. It has been assumed that oxygen consumption decreases approximately equally during hypothermia with either strategy, although there are biochemical reasons to hypothesize that oxygen consumption would be better maintained with the alpha-stat strategy. We also hypothesized that venous oxygen tension would be lower with the more alkaline alpha-stat strategy than with the pH-stat acid-base strategy, because of the Bohr effect. We tested these hypotheses by placing 10 anesthetized immature domestic pigs on cardiopulmonary bypass. We measured whole body oxygen consumption and myocardial oxygen consumption. Control measurements were made at 37 degrees C. Then the animals were cooled to 27 degrees C and the measurements were repeated. The alpha-stat strategy (pH 7.554 +/- 0.020 at 27 degrees C) was used in five animals and five animals received pH-stat management (pH 7.409 +/- 0.012 at 27 degrees C). Whole body and myocardial oxygen consumption rate decreased in both groups, but more so in the alpha-stat animals than in the pH-stat animals. The unexpectedly high oxygen consumption in the pH-stat animals also resulted in a lower than expected venous oxygen tension. Thus the effect of hypothermia in reducing oxygen consumption was less pronounced with pH-stat acid-base management.