Temperature during coronary artery bypass surgery affects quality of life.

BACKGROUND: The objective of this study was to examine the effects of temperature on a variety of indices of psychologic adjustment and quality of life. METHODS: A total of 209 patients randomly received normothermic (warm) or hypothermic (cold) conditions during coronary artery bypass surgery (CABS), and a number of physical, social, and psychologic measures were assessed before as well as 6 weeks and 6 months after CABS. RESULTS: Repeated measures analyses of covariance revealed significant temperature group main effects for anxiety (p = 0.008) and depression (p = 0.039), with the normothermic group obtaining lower anxiety and depression levels than the hypothermic group at both 6 weeks and 6 months after surgery. Additionally, among patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition (p = 0.012). No temperature group differences were observed on other quality of life indices. CONCLUSIONS: The results of the present study indicate that hypothermic conditions during CABS are associated with higher levels of emotional distress after CABS than normothermic conditions, particularly for patients with greater stress to begin with.

Cerebral emboli and serum S100beta during cardiac operations.

BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage in a number of clinical settings. The purpose of this investigation was to determine the correlation between cerebral microemboli and S100beta levels during cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were divided into five time periods: (1) incision to aortic cannulation; (2) aortic cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release; (4) cross-clamp release to decannulation; and (5) decannulation to chest closure. The level of S100beta (n = 156) was measured at baseline, at the end of cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release. RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time, cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary bypass time was univariately associated with S100beta level, it became nonsignificant in a multivariable model that included age and cross-clamp time. CONCLUSIONS: The correlation of S100beta level with emboli measured during cannulation (time period 2) supports the hypothesis that cannulation is a high-risk time period for cerebral injury.

Transcranial Doppler blood flow velocity versus 133Xe clearance cerebral blood flow during mild hypothermic cardiopulmonary bypass.

OBJECTIVE: Transcranial doppler (TCD) is used during cardiopulmonary bypass (CPB) to assess cerebral emboli and to estimate cerebral perfusion. We sought to compare TCD middle cerebral artery blood flow velocity (Vmca) to 133Xe clearance cerebral blood flow (CBF) measurements during mild hypothermic CPB thus determining its utility in cerebral perfusion assessment. METHODS: Thirty-four patients undergoing mild hypothermic CPB (35 degrees C) were studied and had comparisons of Vmca and 133Xe CBF at three time intervals, 10, 30 and 60 min after the institution of CPB. Linear regression analysis was performed on data from each of the 3 intervals as well as for pooled data from all 3 periods. RESULTS: The correlation coefficients for the 3 time periods were, r = 0.32 (p = 0.12), r = 0.32 (p = 0.11), r = 0.48 (p = (0.02), respectively. The pooled data correlation had a coefficient of 0.34 (p = 0.003). CONCLUSION: These findings suggest that TCD Vmca is a relatively poor correlate of CBF during mild hypothermic CPB.

Cardiopulmonary bypass time does not affect cerebral blood flow.

BACKGROUND: A time-dependent decline in cerebral blood flow (CBF) has been reported in cardiac surgical patients despite stable pump flows and arterial carbon dioxide tension. Other studies have failed to support these hypothermic cardiopulmonary bypass (CPB) results, showing preservation of CBF during CPB. The purpose of the study was to define the influence of mildly hypothermic CPB duration on CBF. METHODS: Cerebral blood flow was measured using xenon-133 washout and alpha-stat blood gas management during nonpulsatile CPB. Cerebral blood flow measurements were made after the initiation of CPB and near the end of bypass during pump flows of 2.4 L.min-1.m-2. RESULTS: Fifty-two coronary artery bypass patients were studied. The average time between CBF measurements was 54 +/- 20 minutes (mean +/- standard deviation), with a range of 10 to 100 minutes. Temperature and arterial carbon dioxide tension were controlled: after the initiation of CPB, temperature was 35.5 degrees +/- 0.4 degree C and carbon dioxide tension was 37 +/- 2.8 mm Hg; whereas near the end of bypass temperature was 35.6 degrees +/- 0.5 degree C and carbon dioxide tension was 36 +/- 2.3 mm Hg. We found no correlation between CBF and time on CPB (p = 0.47; r = 0.101), in contrast to other studies suggesting that CPB duration may intrinsically affect CBF. CONCLUSIONS: Our experimental results include the following: (1) during mildly hypothermic bypass, CBF does not decrease in relation to time and (2) cerebral flow-metabolism coupling is intact at 35 degrees C.

Pharmacologic electroencephalographic suppression during cardiopulmonary bypass: a comparison of thiopental and isoflurane.

UNLABELLED: In this study, we examined the cerebral oxygenation effects of two methods of pharmacologic burst suppression during cardiopulmonary bypass (CPB) in valvular heart surgery patients. Patients were randomly entered into one of three groups: control (n = 13, fentanyl and midazolam), control plus burst suppression doses of thiopental (n = 15), or control plus burst suppression doses of isoflurane (n = 16). Burst suppression (80% suppression) was accomplished in the thiopental and isoflurane groups 15 min before aortic cannulation and was maintained through aortic decannulation. Cerebral physiologic measurements were made during hypothermia (27-28 degrees C) and on rewarming to 36 degrees C. During hypothermia, burst suppression produced significant (P < 0.005) differences with regard to cerebral vascular resistance (P = 0.003), cerebral arterial venous oxygen difference [C(a-v)O2] (P = 0.032), cerebral blood flow (CBF) (P = 0.009), and cerebral oxygen delivery (P = 0.027). There was a similar pattern on rewarming, with groups differing significantly (P < 0.05) with respect to CBF (P = 0.016), cerebral vascular resistance (P = 0.008), oxygen delivery (P = 0.004), C(a-v)O2 (P = 0.043), and cerebral oxygen extraction (P = 0.046). Rewarming rates were similar among groups. There was no difference in neurologic outcome or requirement for inotropic support among groups. The time to awakening was increased (P = 0.0005) in the thiopental group. The thiopental group had lower cerebral oxygen delivery, but not lower cerebral metabolic rate of oxygen consumption, compared with the control group, resulting in widening C(a-v)O2 during CPB. This lack of coupling of oxygen delivery and consumption suggests that pharmacologic neuroprotective mechanisms are complex and involve more than an improvement in the ratio of global cerebral oxygen supply to demand. IMPLICATIONS: This study demonstrates that the balance of cerebral oxygen delivery to consumption during cardiopulmonary bypass is altered differently by thiopental and isoflurane. As others have noted, it seems that cerebral protection is more complex than a simple improvement in the balance of oxygen delivery and consumption.

Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center.

BACKGROUND: Changes in memory and cognition frequently follow cardiac operations. We hypothesized that patients with the apolipoprotein E-epsilon 4 allele are genetically predisposed to cognitive dysfunction after cardiac operations. METHODS: The apolipoprotein E-epsilon 4 allele was evaluated as a predictor variable for postoperative cognitive dysfunction in 65 patients undergoing cardiac bypass grafting at Duke University Medical Center. The primary outcome measure was performance on a cognitive battery administered preoperatively and at 6 weeks postoperatively. RESULTS: In a multivariable logistic regression analysis including apolipoprotein E-epsilon 4, preoperative score, age, and years of education, a significant association was found between apolipoprotein E-epsilon 4 and change in cognitive test score in measures of short-term memory at 6 weeks postoperatively. Patients with lower educational levels were more likely to show a decline in cognitive function associated with the apolipoprotein E-epsilon 4 allele. CONCLUSIONS: This study suggests that apolipoprotein E genotype is related to cognitive dysfunction after cardiopulmonary bypass. Cardiac surgical patients may be susceptible to deterioration after physiologic stress as a result of impaired genetically determined neuronal mechanisms of maintenance and repair.

Continuous jugular venous versus nasopharyngeal temperature monitoring during hypothermic cardiopulmonary bypass for cardiac surgery.

STUDY OBJECTIVE: To compare jugular venous to nasopharyngeal temperature during hypothermic cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Tertiary care teaching hospital. PATIENTS: 5 ASA physical status IV patients (40 to 65 years of age) having cardiac surgery with hypothermic CPB. INTERVENTIONS, MEASUREMENTS AND MAIN RESULTS: Jugular venous and nasopharyngeal temperatures were recorded throughout the procedure with comparisons made during four time periods: pre-CPB, during CPB, during rewarming, and post-CPB. The patients underwent 85.8 +/- 45.8 minutes (mean +/- SD) of hypothermic CPB, cooling to 26.3 +/- 7.6 degrees C (nasopharyngeal) followed by rewarming at 0.35 +/- 0.1 degree C (nasopharyngeal)/min. There was a high degree of precision between the two temperature sites, but marked differences in bias. In particular, temperature bias was more pronounced during rewarming from CPB compared with other time periods (p < 0.05) where jugular venous temperature was greater than nasopharyngeal temperature by 3.4 degrees C. CONCLUSION: Nasopharyngeal temperature underestimates jugular venous temperature during rewarming from hypothermic CPB. As a result, the brain may be exposed to periods of hyperthermia, possibly increasing the risk of neurologic injury associated with CPB.

Effect of temperature during cardiopulmonary bypass on gastric mucosal perfusion.

The purpose of our study was to prospectively study the splanchnic response to hypothermic and tepid cardiopulmonary bypass (CPB) using alphastat management of arterial blood-gas tensions. Twenty-four patients for elective CABG surgery were allocated randomly to tepid (35-36 degrees C) or hypothermic (30 degrees C) bypass groups. Measurements were made at four times: (1) baseline, (2) stable during CPB (inflow temperature = nasopharyngeal temperature) 30 degrees C for hypothermic patients, bypass +20 min for tepid patients, (3) 10 min before the end of bypass, (4) after bypass, skin closure. Both groups demonstrated a significant reduction in gastric intramucosal pH (pHim) from time 1 to time 4 and there was no difference in the incidence of a low pHim between the tepid and cold groups (4/12 vs 3/12; ns) at time 4. pHim was significantly lower in the tepid groups at time 3 (P = 0.03) but this discrepancy may have been because of an artefactually high pHim in the cold group. There was a significantly higher incidence of postoperative non-cardiac complications in patients who had a low pHim at time 4 (P = 0.0008). Therefore, we conclude that although the temperature during CPB had a transient effect on pHim it is unlikely to be a major determinant in the pathogenesis of gut mucosal hypoperfusion after bypass.

Effect of perfusion pressure on cerebral blood flow during normothermic cardiopulmonary bypass.

BACKGROUND: We have recently shown that during hypothermic cardiopulmonary bypass (CPB), cerebral autoregulation has a positive slope such that for every 10 mm Hg change in pressure, a 0.86 mL.100 g-1.min-1 change in cerebral blood flow (CBF) is predicted. The purpose of this study was to define the influence of mean arterial blood pressure (MAP) on CBF during normothermic CPB. METHODS AND RESULTS: CBF was measured by use of 133Xe washout and alpha-stat blood gas management during nonpulsatile CPB. CBF measurements were made at a pump flow of 2.4 L.min-1.m-2 at stable normothermia and approximately 15 minutes later after the MAP was increased or decreased > or = 20%. A third data set was recorded after the pressure was returned to the initial value. Forty-five patients were entered into the study. Temperature was held constant. We found a significant effect (P = .016) of change in MAP on change in CBF during normothermic CPB. For a 10 mm Hg increase in MAP, an increase in CBF of 1.78 mL.100 g-1.min-1 is predicted. Along with change in CBF, significant increases in both cerebral metabolic rate and cerebral oxygen delivery were observed. CONCLUSIONS: This information, along with our previous data shows that autoregulation during CPB has a positive slope that is greater with normothermia than hypothermia. Although it is unlikely that these small changes in flow are an important primary effect in the development of hypoperfusion, increased metabolic rate with increased CBF may indicate pressure-dependent collateral flow potentially in regions embolized during CPB.

Defining neuropsychological dysfunction after coronary artery bypass grafting.

BACKGROUND: Despite the large body of literature documenting the presence of cognitive decline after coronary artery bypass grafting, there is little consensus as to the frequency and extent of cognitive impairment. One potential reason for this lack of agreement is the absence of uniform criteria for assessing cognitive decline. METHODS: Two hundred thirty-two patients underwent cognitive testing the day before operation and were examined before discharge, and at 6 weeks and 6 months after grafting. For comparative purposes, five different sets of criteria were used to define cognitive decline. RESULTS: There was little agreement between the criteria as to which patients declined at each test period. The incidence of decline ranged from 66% to 15.3% before discharge, 34% to 1.1% at 6 weeks, and 19.4% to 3.4% at 6 months. CONCLUSIONS: A large variation in reported incidence of cognitive decline after coronary artery bypass grafting can be attributed to the different criteria used to define cognitive impairment.

Cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. CNS Subgroup of McSPI.

Central nervous system (CNS) complications are common after cardiac surgery. Death due to cardiac causes has decreased, but the number of deaths due to CNS injury has increased. As a first stage in the evaluation of its cerebral protection potential, we evaluated the cerebral physiologic effects of burst suppression doses of propofol during nonpulsatile cardiopulmonary bypass. Thirty patients without history of cerebral vascular disease were randomized to two study groups: control group (n = 15) who received sufentanil and vecuronium, or propofol group (n = 15) who received the control anesthetic and propofol infused to maintain electroencephalogram (EEG) burst suppression. Catheters were placed in the radial artery and right jugular bulb for sampling of systemic arterial and jugular bulb venous blood. 133Xe clearance was used to determine cerebral blood flow (CBF) at the start of normothermic bypass, during stable hypothermia, and when rewarmed to 35-37 degrees C nasopharyngeal temperature. Pharmacologic burst suppression with propofol produced a statistically significant reduction in CBF, cerebral oxygen delivery (DO2), and cerebral metabolic rate (CMRO2) at each measurement interval (P < 0..05 vs control). Cerebral arterial venous oxygen difference (C(a-v)O2), and jugular bulb venous oxygen saturation (SJvO2) were not statistically different between groups, indicating maintenance of cerebral metabolic autoregulation (coupling). The reduction in CBF and CMRO2, prominent during the normothermic phases of cardiopulmonary bypass (CPB), indicates a potential for propofol to reduce cerebral exposure to the embolic load during CPB.

Differential age effects of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery.

Central nervous system dysfunction is a common consequence of otherwise uncomplicated cardiac surgery. Many mechanisms have been postulated for the cognitive dysfunction that is part of these neurologic sequelae. The purpose of our investigation was to evaluate the effects of mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) and the rate of rewarming on cognitive decline after cardiac surgery. Two hundred thirty-seven patients completed preoperative and predischarge neuropsychologic testing. MAP and temperature were recorded at 1-min intervals using an automated anesthesia record keeper. MAP area less than 50 mm Hg (time and degree of hypotension), as well as the maximal rewarming rate, were determined for each patient. Multivariable linear regression revealed that the rate of rewarming and MAP were unrelated to cognitive decline. However, interactions significantly associated with cognitive decline were found between age and MAP area less than 50 mm Hg on one measure, and between age and rewarming rate in another, identifying susceptibility of the elderly to these factors. Although MAP and rewarming were not the primary determinates of cognitive decline in this surgical population, hypotension and rapid rewarming contributed significantly to cognitive dysfunction in the elderly.

Jugular bulb saturation and mixed venous saturation during cardiopulmonary bypass.

Systemic venous oxygen saturation is clinically used as an indicator of a satisfactory oxygen supply demand balance on cardiopulmonary bypass (CBP). Cerebral desaturation has been associated with postoperative cognitive dysfunction and has an incidence of 17% to 23% on bypass. We tested the hypothesis that systemic venous saturation did not correlate with jugular bulb venous saturation. Blood was drawn from the radial artery, jugular bulb catheter, and venous return line for determination of pH, oxygen tension and saturation, and carbon dioxide tension at four times during bypass: warm 1 (following initiation of CPB); cold 1 (stable hypothermia); cold 2 (hypothermia prior to rewarm); and warm 2 (nasopharyngeal temperature 36 degrees C to 37 degrees C). Correlations of jugular bulb and systemic venous saturation at cold 1 were r = 0.29, r2 = 0.08, and p = 0.0005, and at warm 2 were r = 0.22, r2 = 0.05, and p = 0.007. We conclude that systemic saturation is a poor indicator of cerebral saturation. The poor association of jugular and systemic pump venous saturations underscores our inability to evaluate adequacy of cerebral perfusion. Jugular saturation is lower than pump venous return blood, especially at times of lower oxygen delivery, thus either continuous invasive or noninvasive evaluation of cerebral oxygenation is required to evaluate the adequacy of cerebral perfusion.

Predictors of cognitive decline after cardiac operation.

Despite major advances in cardiopulmonary bypass technology, surgical techniques, and anesthesia management, central nervous system complications remain a common problem after cardiopulmonary bypass. The etiology of neuropsychologic dysfunction after cardiopulmonary bypass remains unresolved and is probably multifactorial. Demographic predictors of cognitive decline include age and years of education; perioperative factors including number of cerebral emboli, temperature, mean arterial pressure, and jugular bulb oxygen saturation have varying predictive power. Recent data suggest a genetic predisposition for cognitive decline after cardiac surgery in patients possessing the apolipoprotein E epsilon-4 allele, known to be associated with late-onset and sporadic forms of Alzheimer's disease. Predicting patients at risk for cognitive decline allows the possibility of many important interventions. Predictive power and weapons to reduce cellular injury associated with neurologic insults lend hope of a future ability to markedly decrease the impact of cardiopulmonary bypass on short-term and long-term neurologic, cognitive, and quality-of-life outcomes.

Methodological issues in the assessment of neuropsychologic function after cardiac surgery.

This report reviews critical issues facing investigators interested in neuropsychologic sequelae after cardiac operations: (1) experimental design; (2) selective attrition; (3) selection of instruments; (4) moderating factors; (5) definitions of cognitive decline; (6) statistical analysis; and (7) clinical significance. Implications for further research in the area are discussed.

Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass.

Inadequate cerebral oxygenation during cardiopulmonary bypass may lead to postoperative cognitive dysfunction in patients undergoing cardiac operations. A psychological test battery was administered to 255 patients before cardiac operation and just before hospital discharge. Postoperative impairment was defined as a decline of more than one standard deviation in 20% of tests. Variables significantly (p < 0.05) associated with postoperative cognitive impairment are baseline psychometric scores, largest arterial-venous oxygen difference, and years of education. Jugular bulb hemoglobin saturation is significant if it replaces arterial-venous oxygen difference in the model. Factors correlated with jugular bulb saturation at normothermia were cerebral metabolic rate of oxygen consumption (r = -0.6; p < 0.0005), cerebral blood flow (r = 0.4; p < 0.0005), oxygen delivery (r = 0.4; p < 0.0005), and mean arterial pressure (r = 0.15; p < 0.05). Three measures were significantly related to desaturation at normothermia and at hypothermia as well: greater cerebral oxygen extraction, greater arterial-venous oxygen difference, and lower ratio of cerebral blood flow to arterial-venous oxygen difference. We conclude that cerebral venous desaturation occurs during cardiopulmonary bypass in 17% to 23% of people and is associated with impaired postoperative cognitive test performance.

Effect of aging on cerebral autoregulation during cardiopulmonary bypass. Association with postoperative cognitive dysfunction.

BACKGROUND: Age is a predictor of cognitive dysfunction after cardiac surgery, but the mechanism is unknown. The purpose of our study was to determine whether age-related decrements in cognition are associated with cerebral blood flow (CBF) autoregulation during cardiopulmonary bypass (CPB). METHODS AND RESULTS: Cognitive function testing was completed before surgery and before hospital discharge in 215 patients undergoing elective coronary artery bypass grafting (CABG) surgery. The battery consisted of seven tests with nine measures designed to evaluate memory, mood changes, and visuomotor speed and function. Pressure-flow and metabolic-flow cerebral autoregulation during hypothermic cardiopulmonary bypass were determined using the 133Xe clearance CBF method and radial artery and jugular bulb effluent to calculate cerebral metabolic rate (CMRO2) and cerebral AV difference (C[AV]O2). Pressure-flow autoregulation was tested by using two CBF measurements at stable hypothermia: one at stable mean arterial pressure (MAP) and the second 15 minutes later when MAP had increased or decreased > or = 20%. Metabolism-flow autoregulation was tested by varying the temperature (CMRO2) and measuring the coupling of CBF and CMRO2. Individual patient autoregulation was correlated with changes in cognitive measures. Cognitive performance declined in 6 of 9 measures after CABG surgery. Age predicted cognitive decline in 7 of 9 measures; short-term memory showed the greatest effect of age. Pressure-flow autoregulation during hypothermic CPB showed a small but significant (P < .0001) effect of pressure on CBF. There was no effect of age on the slope of CBF response to changes in MAP (pressure-flow autoregulation). There was a major effect of temperature on CBF during CPB (P < .0001). Coupling CBF and CMRO2 with changing temperature was unaffected by age. Changes in cognition were not associated with measures of cerebral autoregulation. However, increasing C(AV)O2 is associated with cognitive deficits in 5 of 9 measures; these associations were independent of age. CONCLUSIONS: Increased age predisposes to impaired cognition after cardiac surgery. This decline in cognitive function in the elderly is not associated with age-related changes in cerebral blood flow autoregulation. The association of increased oxygen extraction with decline in some measures of cognitive function suggests that an imbalance in cerebral tissue oxygen supply, which is unrelated to age, contributes to acute cognitive dysfunction after cardiac surgery. Cognitive dysfunction after CPB in the elderly cannot be explained by impaired CBF autoregulation.

Effect of altering pump flow rate on cerebral blood flow and metabolism in infants and children.

The effects of reduced pump flow rate (PFR) on cerebral blood flow, cerebral oxygen consumption (CMRO2), oxygen extraction, cerebral vascular resistance, and total body vascular resistance were examined in 27 pediatric patients during hypothermic cardiopulmonary bypass (hCPB). During steady state hCPB the extracorporeal flows were randomly adjusted to a conventional PFR and a reduced PFR for each patient. The reduced pump flow rates were dictated by surgical needs. Cerebral blood flow measured using Xenon 133 clearance, and CMRO2 and oxygen extraction were calculated. Our results demonstrated that cerebral blood flow and CMRO2 are unchanged if pump flow rates are reduced by 35% to 45% of conventional PFRs at moderate and deep hypothermic temperatures. Reductions in PFR of 45%-70% from conventional PFRs affect the brain differently during either moderate or deep hCPB. At moderate hCPB (26 degrees to 29 degrees C), reductions in PFRs of 45% to 70% resulted in a significant decrease in cerebral blood flow and CMRO2, whereas oxygen extraction increased in a compensatory manner. During deep hCPB (18 degrees to 22 degrees C), PFR reductions of 45% to 70% of conventional PFR significantly reduced cerebral blood flow and CMRO2 but did not increase oxygen extraction, suggesting that at deep hypothermic temperatures, cerebral blood flow and CMRO2 exceed cerebral metabolic needs. Cerebral vascular resistance increased significantly with decreasing temperature but was not affected by pump flow reductions. We have derived indices for minimal acceptable low-flow cardiopulmonary bypass based on the known effects of temperature on cerebral metabolism and have speculated on its utility based on our limited data and a literature review.

Cerebral blood flow and metabolism during cardiopulmonary bypass.

Although much has been learned about cerebral physiology during CPB in the past decade, the role of alterations in CBF and CMRO2 during CPB and the unfortunately common occurrence of neuropsychologic injury still is understood incompletely. It is apparent that during CPB temperature, anesthetic depth, CMRO2, and PaCO2 are the major factors that effect CBF. The systemic pressure, pump flow, and flow character (pulsatile versus nonpulsatile) have little influence on CBF within the bounds of usual clinical practice. Although cerebral autoregulation is characteristically preserved during CPB, untreated hypertension, profound hypothermia, pH-stat blood gas management, diabetes, and certain neurologic disorders may impair this important link between cerebral blood flow nutrient supply and metabolic demand (Figure 5). During stable moderate hypothermic CPB with alpha-stat management of arterial blood gases, hypothermia is the most important factor altering cerebral metabolic parameters. Autoregulation is intact and CBF follows cerebral metabolism. Despite wide variations in perfusion flow and systemic arterial pressure, CBF is unchanged. Populations of patients have been identified with altered cerebral autoregulation. To what degree the impairment of cerebral autoregulation contributes to postoperative neuropsychologic dysfunction is unknown. It must be emphasized that not the absolute level of CBF, but the appropriateness of oxygen delivery to demand is paramount. However, the assumption that the control of cerebral oxygen and nutrient supply and demand will prevent neurologic injury during CPB is simplistic. A better understanding of CBF, CMRO2, autoregulation and mechanism(s) of cerebral injury during CPB has lead to a scientific basis for many of the decisions made regarding extracorporeal perfusion.