Renal hypoxanthine balance in cardiac surgery: effects of felodipine

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

The effects of deep hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral blood flow in infants and children

Cardiopulmonary bypass management in infants and children involves extensive alterations in temperature, hemodilution, and perfusion pressure, with occasional periods of circulatory arrest. Despite the use of these biologic extremes of temperature and perfusion, their effects on cerebral blood flow are unknown. This study was designed to examine the relationship of mean arterial pressure and nasopharyngeal temperature to cerebral blood flow during deep hypothermic cardiopulmonary bypass (18 degrees to 22 degrees C) with and without periods of total circulatory arrest. Cerebral blood flow was measured before, during, and after deep hypothermic cardiopulmonary bypass using xenon clearance techniques in 25 children, aged 2 days to 60 months. Fourteen patients underwent repair with circulatory arrest. There was a highly significant correlation of cerebral blood flow with temperature during cardiopulmonary bypass (p = 0.007). During deep hypothermic bypass there was a significant association between cerebral blood flow and mean arterial pressure (p = 0.027). In infants undergoing repair with deep hypothermia alone, cerebral blood flow returned to prebypass levels in the rewarming phase of bypass. However, in patients undergoing repair with circulatory arrest, no significant increase in cerebral blood flow during rewarming or even after bypass was observed (p = 0.01). These data show that deep hypothermic cardiopulmonary bypass significantly decreases cerebral blood flow because of temperature reduction. Under conditions of deep hypothermia, cerebral pressure-flow autoregulation is lost. This study also demonstrates that cerebral reperfusion after deep hypothermia is impaired if the patient is exposed to a period of total circulatory arrest.     

Continuous measurement of oxygen consumption during cardiopulmonary bypass: description of the method and in vivo observations

BACKGROUND: Systemic oxygen consumption is not routinely measured during cardiopulmonary bypass, despite its potential benefits. We aimed to develop a noninvasive method to continuously measure oxygen consumption using respiratory mass spectrometry during hypothermic cardiopulmonary bypass in pigs. METHODS: Nine pigs weighing 18.5 (1.6) kg underwent hypothermic (32 degrees C) cardiopulmonary bypass for 180 minutes with 120 minutes of aortic cross clamping. An AMIS 2000 mass spectrometer (Innovision A/S, Odense, Denmark) was adapted for the on-line measurement of oxygen consumption by sampling the inlet and outlet gases of the membrane oxygenator together with measurement of the "expired" gas volume. RESULTS: Active cooling for 60 minutes reduced the venous blood temperature by 2.9 (0.8) degrees C and VO(2) by 0.70 (0.33) mL/kg/min. The 40-minute active rewarming restored the venous blood temperature by 4.4 (0.4) degrees C and oxygen consumption increased by 1.36 (0.33) mL/kg/min. There was wide interanimal variability, however, particularly at higher venous blood temperatures. Immediately after the release of aortic cross clamp, there was a noticeably acute increase in oxygen consumption in all the pigs (0.64 [0.21] mL/kg/min). CONCLUSIONS: A simple and safe adaptation of mass spectrometry allows continuous measurement of oxygen consumption during hypothermic cardiopulmonary bypass. The wide interindividual variations observed in this pilot study underscore the need to more accurately describe changes in oxygen consumption and how they are affected by temperature, oxygen delivery, and other interventions during cardiopulmonary bypass. As such, the technique may have an important role in clinical research and management of oxygen transport in patients undergoing cardiac surgery.     

Hemodilution elevates cerebral blood flow and oxygen metabolism during cardiopulmonary bypass in piglets

BACKGROUND: Hemodilution continues to be widely used during cardiopulmonary bypass (CPB) for both adults and children. Previous studies with nonbypass models have suggested that an increase in cerebral blood flow (CBF) compensates for the reduced oxygen-carrying capacity; however, this increased CBF is achieved by an increase in cardiac output. We hypothesized that even with the fixed-flow perfusion of CPB, CBF would be increased during hemodilution. METHODS: Two experiments were conducted and analyzed separately. In each experiment, 10 piglets were randomized to two different groups, one with a total blood prime yielding a high hematocrit (25% or 30%), and the other with a crystalloid prime resulting in a low hematocrit (10% or 15%). Animals were cooled with pH-stat strategy at full flow (100 or 150 mL.kg(-1).min(-1)) to a nasopharyngeal temperature of 15 degrees C, a period of low flow (50 mL.kg(-1).min(-1)) preceding deep hypothermic circulatory arrest (45 or 60 minutes), and a period of rewarming at full flow. Cerebral blood flow was measured at the beginning of CPB, at the end of cooling, at the end of low flow, 5 minutes after the start of rewarming, and at the end of rewarming by injection of radioactive microspheres. RESULTS: Mean arterial pressure was significantly greater with higher hematocrit at each time point (p< 0.05). Cerebral blood flow and the cerebral metabolic rate of oxygen decreased during cooling and further during low flow bypass but were significantly greater with lower hematocrit during mild hypothermia and at the end of rewarming (p< 0.05). CONCLUSIONS: Hemodilution is associated with decreased perfusion pressure, increased CBF and increased the cerebral metabolic rate of oxygen during hypothermic CPB.     

Pharmacologic EEG suppression during cardiopulmonary bypass: cerebral hemodynamic and metabolic effects of thiopental or isoflurane during hypothermia and normothermia

We have determined the effects of thiopental or isoflurane upon cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) when these agents are used in sufficient dose to attain a deep burst suppression pattern on the electroencephalogram (EEG) during hypothermic and normothermic cardiopulmonary bypass (CPB). Thirty-one patients undergoing coronary artery bypass graft surgery were anesthetized with fentanyl 0.1 mg X kg-1, and were randomly allocated to one of three groups: control (no further anesthetics during bypass and continuous EEG activity), thiopental treatment (EEG suppression), or isoflurane treatment (EEG suppression). Hypothermia (25-29 degrees C) was routinely induced at onset of nonpulsatile cardiopulmonary bypass. In the treatment groups, thiopental or isoflurane were used during bypass to achieve a deep burst suppression pattern. Cerebral blood flow and cerebral metabolic rate for oxygen were determined during hypothermia and upon rewarming to normothermia (37 degrees C). Pharmacologic EEG suppression with either isoflurane or thiopental was associated with lower cerebral metabolic rate than control values during both hypothermic and normothermic bypass. However, only thiopental-induced EEG suppression was associated with lower cerebral blood flow than control. Cerebral blood flow during isoflurane-induced EEG suppression was similar to control values in spite of the reduced cerebral metabolic rate.     

Oxygen consumption after hypothermic cardiopulmonary bypass: the effect of continuing a propofol infusion postoperatively

OBJECTIVE: To evaluate the effect of a fixed rate of infusion of propofol on total body oxygen consumption during the postoperative rewarming phase after cardiopulmonary bypass. DESIGN: Prospective, randomized, controlled study. SETTING: Cardiac intensive care unit, university hospital. PARTICIPANTS: Twenty-four male and female patients undergoing elective first-time coronary artery bypass graft surgery. INTERVENTIONS: Total body oxygen consumption was measured using a pulmonary artery catheter and thermodilution during postoperative rewarming. Twelve patients had propofol infused at 2 mg/kg/h for 4 hours or until rewarmed. MEASUREMENTS AND MAIN RESULTS:Total body oxygen consumption was reduced in the propofol group compared with the control group. Oxygen consumption was a median of 30.0 mL/min/m(2) less in the patients receiving propofol (p = 0.01). One patient receiving propofol shivered compared with 4 in the control group (p = 0.14). CONCLUSION: Administration of propofol during postoperative rewarming reduces total body oxygen consumption and may reduce shivering.     

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

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

Effect of rewarming speed during hypothermic cardiopulmonary bypass on cerebral pressure-flow relation

BACKGROUND: Cerebral blood flow is less dependent on arterial blood pressure during hypothermic cardiopulmonary bypass (CPB) compared to warm CPB. Fast rewarming has a more pronounced effect on cognitive performance in the elderly and causes an increased arterio-jugular oxygen content difference. We studied the effect of rewarming and rewarming speed on cerebral pressure-flow relation in adult patients undergoing elective coronary artery bypass surgery with mild hypothermic CPB. METHODS: Fifty patients were randomly assigned to either a slow rewarming strategy (0.24 degrees C/min) or a fast rewarming strategy (0.5 degrees C/min). Cerebral pressure-flow relation was assessed by a transcranial Doppler derived index for cerebral pressure-flow relation (Pressure-flow Index, PFI). The effect of rewarming speed on cerebral pressure-flow relation was assessed by comparing the absolute PFI value after rewarming between the two treatment groups. RESULTS: The mean PFI decreased significantly from 0.73 (standard deviation: 0.28) before rewarming to 0.54 (0.35) after rewarming in the slow rewarming group and from 0.63 (0.29) to 0.48 (0.30) in the fast rewarming group. Absolute PFI after rewarming was not significantly different (mean PFI difference = 0.06; 95% CI = - 0.13; 0.26) between both rewarming strategies. CONCLUSION: Rewarming from mild hypothermic CPB might result in pressure-dependent cerebral blood flow velocity but rewarming speed did not aggravate the effect of rewarming on pressure-flow dependency.     

Impact of hypothermic selective cerebral perfusion compared with hypothermic cardiopulmonary bypass on cerebral hemodynamics and metabolism.

OBJECTIVE: Hypothermic selective cerebral perfusion (SCP) is widely used for cerebral protection during aortic arch surgery, but the effect of the absence of systemic perfusion on cerebrovascular dynamics it has never been established. This study explored the physiology of prolonged SCP compared to hypothermic cardiopulmonary bypass (HCPB) in pigs. METHODS: In this blinded protocol, 29 juvenile pigs (20-23 kg) were randomized after cooling on cardiopulmonary bypass (CPB) to 20 degrees C. Group I pigs (n=14) underwent 90 min of SCP, while group II (HCPB, n=15) underwent total body perfusion. Fluorescent microspheres were injected during perfusion and recovery, enabling calculation of total and regional cerebral blood flow (CBF). Cerebrovascular resistance (CVR), oxygen consumption and intracranial pressure (ICP) were also monitored. RESULTS: CBF decreased significantly (P=0.0001) during cooling, but remained at significantly higher levels with SCP than with HCPB throughout perfusion and recovery (P<0.0001). CVR was significantly lower with SCP than with HCPB throughout perfusion (P=0.04). Oxygen consumption fell significantly with cooling (P=0.0001), remained low during perfusion, and rebounded promptly with rewarming; with SCP it was significantly higher than with HCPB throughout the perfusion interval (P=0.03), and remained higher thereafter. ICP rose significantly less with SCP than with HCPB (P=0.02). CONCLUSION: We conclude that, compared with HCPB, SCP results in beneficial cerebral vasodilatation, as evidenced by significantly higher CBF and oxygen consumption during SCP, by prompt recovery of oxygen consumption after rewarming, and by significantly lower ICP during perfusion and in the post-bypass period.     

Rapid Rewarming Causes an Increase in the Cerebral Metabolic Rate for Oxygen that Is Temporarily Unmatched by Cerebral Blood Flow: A Study during Cardiopulmonary Bypass in Rabbits

Background: Jugular venous hemoglobin desaturation during the rewarming phase of cardiopulmonary bypass is associated with adverse neuropsychologic outcome and may indicate a pathologic mismatch between cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2). In some studies, rapid rewarming from hypothermic cardiopulmonary bypass results in greater jugular venous hemoglobin desaturation. The authors wished to determine if rewarming rate influences the temperature dependence of CBF and CMRO2.

Methods: Anesthetized New Zealand white rabbits, cooled to 25 degrees Celsius on cardiopulmonary bypass, were randomized to one of two rewarming groups. In the fast group (n = 9), aortic blood temperature was made normothermic over 25 min. Cerebral blood flow (microspheres) and CMRO2 (Fick) were determined at baseline (25 degrees C), and at brain temperatures of 28 degrees, 31 degrees, 34 degrees, and 37 degrees Celsius during rewarming.

Results: Systemic physiologic variables appeared similar between groups. At a brain temperature of 28 degrees C, CMRO2 was 47% greater in the fast rewarming group than in the slow group (2.2 +/-0.5 vs. 1.5+/-0.2 ml O2 *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.01), whereas CBF did not differ (48+/-18 vs. 49+/-8 ml *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.47). Throughout rewarming, CBF increased as a function of brain temperature but was indistinguishable between groups. Cerebral metabolic rate for oxygen differences between groups decreased as brain temperatures increased.     

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

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

The effect of pump flow on cerebral oxygen metabolism during cardiopulmonary bypass

We evaluated effects of pump flow on cerebral metabolism using transcranial Doppler (TCD) during cardiopulmonary bypass (CPB) in 22 adult patients undergoing coronary artery bypass grafting. All the patients were anesthetized with high dose fentanyl. The pump flow was controlled with non-pulsatile roller pump at 2.2–2.5 L/min/m² in group L and 2.7–3.0 L/min/m² in group H under α-stat acid-base regulation. Pharyngeal temperature was kept at 31°C in steady CPB state. Mean velocity of middle cerebral artery (MCAV) was monitored with TCD fixed on the temple continuously. Cerebral oxygen consumption was estimated by relating the difference in oxygen content between arterial and venous (jugular bulb) blood (AVDO₂) to flow velocity. In group L, blood oxygen saturation of jugular bulb (SjO₂) was stable during hypothermic period, but decreased significantly during rewarming period. In group H, SjO₂ was significantly increased with cooling, but went down to preoperative level during rewarming period. Significant difference of SjO₂ between two groups was noticed in rewarming period (52.9 ± 10.0% in group L and 65.6 ± 11.8% in group H, p=0.0133). MCAV tended to decrease with cooling and increase with rewarming, but which was not significant change respectively. Relative cerebral metabolic rate for oxygen (rCMRO₂) was defined as the percent change of the product AVDO₂ and MCAV. In each group, rCMRO₂ was decreased with cooling and increased with rewarming significantly. Especially, rCMRO₂ right after CPB discontinued was increased 1.7 times in L group and 2.0 times in group H as much as that of steady state of CPB. It is suggested that cerebral metabolism should be decreased during cooling to 31°C of pharyngeal temperature, 2.2–2.5 l/min/m² of pump flow was adequate to keep SjO₂ stable. On the other hand, it is necessary to increase pump flow to 2.7–3.0 l/min/m² during rewarming period as cerebral oxygen metabolic demand becomes greater.     

The effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on anterior fontanel pressure in infants

The Ladd transducer was used to measure anterior fontanel pressure in 23 infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest for surgical correction of congenital heart disease. Mean (+/- SD) minimum oesophageal and rectal temperatures of 11.3 +/- 1.5 degrees C and 18.1 +/- 2.2 degrees C respectively were achieved with a mean duration of arrest of 53.4 +/- 13.9 minutes. During reperfusion cardiopulmonary bypass after circulatory arrest, mean anterior fontanel pressure (18.3 +/- 6.4 mmHg) increased above baseline pre-bypass values (10.6 +/- 2.9 mmHg) (p less than 0.005). Mean arterial blood pressure decreased significantly from pre-bypass values (57.0 +/- 11.8 mmHg) during both cooling (38.8 +/- 8.4 mmHg) and rewarming cardiopulmonary bypass (45.8 +/- 8.9 mmHg) (p less than 0.005). These changes were associated with a significant decrease in cerebral perfusion pressure during cooling (27.3 +/- 11.0 mmHg) and rewarming cardiopulmonary bypass (27.5 +/- 10.6 mmHg), compared with baseline pre-bypass values (46.5 +/- 12.3 mmHg) (p less than 0.005). The data demonstrate significant but transient decreases in cerebral perfusion pressure during cooling and rewarming bypass.     

Pharmacologic cerebral capillary blood flow improvement after deep hypothermic circulatory arrest: an intravital fluorescence microscopy study in pigs

BACKGROUND: Despite meticulous investigation of bypass techniques for deep hypothermic circulatory arrest, unfavorable long-term neurologic deficits have been well documented. Our aim was to improve brain perfusion by reducing platelet plugging with a glycoprotein IIb/IIIa inhibitor (eptifibatide) in an experimental model of deep hypothermic circulatory arrest-reperfusion in pigs. METHODS: Two groups of 12 piglets each (eptifibatide group [eptifibatide + unfractionated heparin] vs UFH group [only unfractionated heparin]) underwent 10 minutes of normothermic bypass, 40 minutes of cooling during cardiopulmonary bypass (hematocrit, 30%; cardiopulmonary bypass flow, 100 mL x kg(-1) x min(-1)), 60 minutes of circulatory arrest at 15 degrees C, and a 40-minute rewarming period. Intravital fluorescence microscopy of pial vessels at set intervals was performed. RESULTS: During the cooling period, there was a tendency toward reduced functional capillary density values without statistical significance in both groups. During reperfusion, the eptifibatide group demonstrated a significantly decreased platelet adhesion and aggregation (at 30 minutes of reperfusion: functional capillary density, 104% +/- 3% vs 77% +/- 4% relative to baseline, P = .02; red blood cell velocity, 0.65 vs 0.30 mm/s, P < .004). A more rapid recovery of tissue oxygenation (P < .001) was documented. Furthermore, a significant microvascular permeability reduction was achieved compared with that seen in the UFH group (P < .02). The use of eptifibatide resulted in fewer ultrastructural changes in hippocampal tissue, which is demonstrated by histologic examination. CONCLUSIONS: Platelet plugging reduction with the glycoprotein IIb/IIIa inhibitor eptifibatide improves cerebral capillary blood flow and reduces cerebral ischemia in the setting of deep hypothermic circulatory arrest. Furthermore, significant endothelial cell injury and perivascular edema reduction can be achieved.     

Is cerebral blood flow/metabolic mismatch during rewarming a risk factor after profound hypothermic procedures in small children?

The relation between cerebral blood flow and oxygen consumption was studied in six children during cardiac operations with profound hypothermia. A combination of topical cooling and core cooling was used to reduce the nasopharyngeal temperature to 15 degrees C. The alpha-stat principle for pH management was used. Blood flow and oxygen consumption decreased significantly with temperature. At a nasopharyngeal temperature of 15 degrees C, blood flow was reduced to 25% of the awake level, corresponding to 34% of the asleep value obtained 15-30 min after intubation. Oxygen consumption decreased to 25% of the asleep value. During stable profound hypothermia, venous saturation in the jugular bulb was at the same level as 15 min after intubation (70%). Markedly lower values were observed during topical cooling, and particularly during rewarming (down to 21%), indicating a mismatch between cerebral blood flow and oxygen consumption. The speed of rewarming correlated with the fall in venous oxygen saturation (rs = 0.82, P less than 0.05). It is suggested that periods of cerebral blood flow/metabolic mismatch during topical cooling and rewarming may explain postoperative cerebral dysfunction after deep hypothermic procedures. A moderate speed of rewarming is advocated.     

The rewarming rate and increased peak temperature alter neurocognitive outcome after cardiac surgery.

Neurocognitive dysfunction is a common complication after cardiac surgery. We evaluated in this prospective study the effect of rewarming rate on neurocognitive outcome after hypothermic cardiopulmonary bypass (CPB). After IRB approval and informed consent, 165 coronary artery bypass graft surgery patients were studied. Patients received similar surgical and anesthetic management until rewarming from hypothermic (28 degrees -32 degrees C) CPB. Group 1 (control; n = 100) was warmed in a conventional manner (4 degrees -6 degrees C gradient between nasopharyngeal and CPB perfusate temperature) whereas Group 2 (slow rewarm; n = 65) was warmed at a slower rate, maintaining no more than 2 degrees C difference between nasopharyngeal and CPB perfusate temperature. Neurocognitive function was assessed at baseline and 6 wk after coronary artery bypass graft surgery. Univariable analysis revealed no significant differences between the Control and Slow Rewarming groups in the stroke rate. Multivariable linear regression analysis, examining treatment group, diabetes, baseline cognitive function, and cross-clamp time revealed a significant association between change in cognitive function and rate of rewarming (P = 0.05). IMPLICATIONS: Slower rewarming during cardiopulmonary bypass (CPB) was associated with better cognitive performance at 6 wk. These results suggest that a slower rewarming rate with lower peak temperatures during CPB may be an important factor in the prevention of neurocognitive decline after hypothermic CPB.     

Relationship of brain blood flow and oxygen consumption to perfusion flow rate during profoundly hypothermic cardiopulmonary bypass. An experimental study

A study was made of the relation of brain blood flow and oxygen consumption to changes in perfusion flow rate during cardiopulmonary bypass at 20 degrees C in nine cynomolgus monkeys. Four perfusion flow rates varying from 0.25 to 1.75 L X min-1 X m-2 were randomly instituted, each for a 10 minute period. At the end of each period, brain arteriovenous oxygen content difference was measured and 15 mu radioactive microspheres were injected into the arterial perfusion line. The brain was then removed and section into anatomic regions and radioactivity was counted. Regional and total brain blood flows were calculated, as was whole brain oxygen consumption. Brain perfusion continued in all areas at all perfusion flow rates. Whole brain blood flow decreased (p less than 0.0001) as perfusion flow rate was reduced (45 +/- 6.5, 41 +/- 7.9, and 23 +/- 2.8 ml X min-1 X 100 gm-1 at 1.5, 1.0, and 0.5 L X min-1 X m-2, respectively). The proportion of the total perfusion delivered to the brain increased (p = 0.003) with decreasing perfusion flow rates (5.4% +/- 0.78%, 7.1% +/- 1.24%, and 8.2% +/- 1.11% at 1.5, 1.0, and 0.5 L X min-1 X m-2, respectively). Brain blood flow resistance remained unchanged (p = 0.4) while that of the remaining body increased (p less than 0.0001). There was a greater reduction of blood flow in the cortical white matter (p = 0.01) than in other regions of the brain. Brain oxygen consumption was the same (p = 0.5) at all perfusion flow rates, related to an increasing percent oxygen extraction with decreasing perfusion flow rate (p less than 0.0001). The data indicate that all areas of the brain remain perfused, even at low perfusion flow rates, during profoundly hypothermic cardiopulmonary bypass, and that brain oxygen consumption is maintained in part by increased oxygen extraction and in part by redistribution of the perfusate from the remaining body to the brain.     

Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Pulsatile assistance for circulatory arrest, low-flow perfusion, and moderate-flow perfusion

The brain tissue pH, oxygen tension, and carbon dioxide tension were experimentally examined during profoundly hypothermic cardiopulmonary bypass with core cooling and core rewarming. Sixty-minute circulatory arrests (n = 28, group I), 120-minute low-flow perfusions (25 ml/kg/min; n = 16, group II), and 120-minute moderate-flow perfusions (50 ml/kg/min; n = 16, group III) were accomplished with and without pulsatile flow. In group I, progressive brain tissue acidosis and hypercapnia were recovered with pulsatile assistance. In group II, brain tissue acidosis and hypercapnia were recovered completely with pulsatile assistance but incompletely without it. In group III mild acidosis was eliminated with pulsatile assistance where the pH was significantly higher than in groups I and II, and brain tissue carbon dioxide pressure was significantly lower than in groups I and II with and without pulsatile assistance. Brain tissue hypoxia was severe in group I, slight in group II, but not found in group III. We concluded that a perfusion flow rate will decide the safe period, and a pulsatile assistance will promote brain protection at any flow rate in profoundly hypothermic cardiopulmonary bypass.     

Cerebral effects of anaesthesia and hypothermia

Cerebral blood flow, cerebral oxygen and glucose consumption, and cerebral lactate and pyruvate release were measured; spectral analysis of the EEG was recorded in 10 male patients who had coronary artery bypass surgery. The measurements were taken to evaluate the effects of fentanyl-midazolam anaesthesia during normothermia and during hypothermic nonpulsatile cardiopulmonary bypass at 26 degrees C venous blood temperature, when a temperature-corrected PaCO2-value of 5.3 kPa was maintained. Anaesthesia with fentanyl 7 micrograms/kg and midazolam 200 micrograms/kg as induction doses, followed by infusions of fentanyl 0.15 micrograms/kg/minute and midazolam 3 micrograms/kg/minute, was characterised by a decrease in fast-wave activity and an increase in high-amplitude, slow-wave activity in the EEG. There was also a decrease in cerebral blood flow (38%), oxygen consumption (22%) and glucose consumption (25%), while lactate and pyruvate production remained unchanged. Hypothermia of 26 degrees C venous blood temperature suppressed EEG almost completely and decreased oxygen and glucose consumption by a further 61% and 54%, respectively, with no changes in lactate and pyruvate production while cerebral blood flow increased by 145%. These results show that the effects of fentanyl-midazolam anaesthesia on cerebral metabolism are enhanced during hypothermic cardiopulmonary bypass while the influence of anaesthesia on cerebral blood flow is overshadowed by the practice of a temperature-corrected acid-base management.     

Oxygenator exhaust capnography: a method of estimating arterial carbon dioxide tension during cardiopulmonary bypass.

An in vivo study was undertaken during hypothermic (28 degrees C) cardiopulmonary bypass to compare oxygenator exhaust capnography as a means of estimating arterial carbon dioxide tension (PaCO2) with bench blood gas analysis. A total of 123 pairs of measurements were made in 40 patients. Oxygenator exhaust capnographic measurements systematically underestimated PaCO2 measured by a bench blood gas analyzer. During the cooling and stable hypothermic phases of cardiopulmonary bypass, the relationship was reasonably accurate, but became far more variable during rewarming. Oxygenator exhaust capnography could be used as an inexpensive means of continuously monitoring PaCO2 during the cooling and stable hypothermic phases of cardiopulmonary bypass but should not be used during rewarming.