Cerebral vascular and metabolic effects of fentanyl and midazolam in young and aged rats

Cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) were measured, and electroencephalogram (EEG) was recorded in young (6-month-old) and aged (28-month-old) rats during ventilation with 70% N2O/30% O2 and following fentanyl or midazolam administration. Cerebral blood flow (CBF) was measured with radioactive microspheres, and cerebral oxygen consumption (CMRO2) was calculated from the arterial-sagittal sinus oxygen content difference and CBF measurements. Fentanyl at the highest dose used (200 micrograms/kg and 400 micrograms.kg-1.h-1) depressed the EEG and decreased CBF 49% and CMRO2 39% in young rats, whereas in old rats, this fentanyl dose decreased CBF 37% and CMRO2 34%, both significantly less than in young rats (P less than 0.05). Midazolam at the highest dose used (5.75 mg/kg) also depressed EEG in both age groups, and decreased CBF 51% and CMRO2 38% in young rats. This depression was significantly less than the 62% decrease in CBF and 59% decrease in CMRO2 produced by midazolam in old rats (P less than 0.05). These results indicate that aging attenuates the cerebrovascular and cerebral metabolic depression produced by fentanyl, but potentiates the same effects produced by midazolam. The enhanced cerebral metabolic depression produced by midazolam in the aged is similar to that seen with phenobarbital, and suggests a similar action of these drugs at the central GABA-benzodiazepine-barbiturate receptor complex.     

Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO2

Measurement of 133Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO2 at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBF was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO2 of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.     

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.     

Cerebral blood flow autoregulation is preserved during cardiopulmonary bypass in isoflurane-anesthetized patients

In 21 patients undergoing elective coronary artery bypass surgery, cerebral blood flow (CBF) was measured during hypothermic nonpulsatile cardiopulmonary bypass to test the hypothesis that isoflurane abolished the mean arterial pressure-CBF relation (pressure-flow autoregulation). Cerebral blood flow was determined by 133Xe clearance. The patients were randomly divided into three groups according to anesthesia during cardiopulmonary bypass: group 1 received midazolam and fentanyl; group 2 received, in addition to midazolam and fentanyl, 0.6% isoflurane; and group 3 received, in addition to midazolam and fentanyl, 1.2% isoflurane. The groups were maintained at a constant temperature, PaO2, PaCO2, and pump flow during CBF measurements. Mean arterial pressure was increased by phenylephrine greater than or equal to 25% after the first CBF determination. Isoflurane decreased mean arterial pressure significantly (P less than 0.05) and was associated with lower CBF. Increasing the mean arterial pressure 29% in group 1, 25% in group 2, and 34% in group 3 had no effect on CBF. We conclude that, within the range studied, pressure-flow CBF autoregulation is preserved during isoflurane anesthesia administered for cardiopulmonary bypass.     

The effects of midazolam on cerebral blood flow and oxygen consumption Interaction with nitrous oxide in patients undergoing craniotomy for supratentorial cerebral tumours

Cerebral blood flow and the cerebral metabolic rate of oxygen were measured in 30 patients during craniotomy for supratentorial cerebral tumours by a modification of the Kety-Schmidt technique using Xenon 133 intravenously. Anaesthesia was induced with midazolam 0.3 mg/kg, fentanyl and pancuronium, and maintained with midazolam as a continuous infusion, fentanyl, pancuronium and nitrous oxide in oxygen or oxygen in air. The concentration of midazolam in the blood of 10 patients was about 300 ng/litre during two measurements; the patients' lungs were ventilated with N2O in oxygen. The concentration of midazolam in the blood of another 10 patients was doubled to about 600 ng/litre during the second flow measurement; the patients' lungs were ventilated with N2O/O2. The concentration of midazolam in the blood of the third group of 10 patients was doubled to 600 ng/litre during the second flow measurement; the patients' lungs were ventilated with oxygen in air. No relationship was found between the dose of midazolam and cerebral blood flow or oxygen consumption. Nitrous oxide in combination with midazolam also had no effect on these variables.     

Brain function and level of consciousness in fentanyl anesthesia in heart surgery

The level of consciousness and the supply/demand ratio of oxygen in the brain was studied in anaesthetized patients undergoing open heart surgery. Anaesthesia was accomplished with intravenous fentanyl; 26 patients received 25 micrograms/kg and 24 patients received 50 micrograms/kg fentanyl. In addition only pancuronium bromide was administered for muscular relaxation; all patients were ventilated with 100% oxygen. The following measurements were made during induction and prior to cardiopulmonary bypass and in the first ten minutes of bypass: 1. EEG with the Klein EEG Analyzer. This instrument permits simultaneous analysis of frequency and amplitude while eliminating muscular artifacts. 2. Cerebral oxygen with the Niroscope. This instrument uses an infrared light beam through the brain to evaluate cerebral oxygen sufficiency. 3. Oxygen supply/demand ratio in the whole body, estimated from mixed venous oxygen saturation measured with a fiberoptic pulmonary artery catheter. Clinical unconsciousness occurred in all patients within about 30 s after the administration of fentanyl. Simultaneously the EEG showed a significant decrease in frequency and an increase in amplitude. With the Niroscope no change in oxygen supply and demand was seen in any patients. This is in contrast to previous studies with thiopental, where changes were seen. A slight increase in mixed venous oxygen saturation was observed. This indicates an increase in the total oxygen supply/demand ratio, probably due to decreased muscle metabolism induced by pancuronium bromide paralysis. From the end of induction until cardiopulmonary bypass a slight increase in cerebral electrical activity was observed; an additional increase occurred in the first ten minutes of bypass.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Disoprivan (propofol) on the circulation and oxygen consumption of the brain and CO2 reactivity of brain vessels in the human

The effects of Disoprivan on cerebral blood flow (CBF), cerebral oxygen consumption, and CO2-reactivity of the cerebral vessels were studied in 11 male patients between 49 and 63 years of age who were about to undergo coronary artery bypass surgery. Mean perfusion pressure was decreased by 25% under anaesthesia by 0.2 mg/kg per minute Disoprivan, but remained within the ranges of autoregulation. CBF decreased by 51% and cerebral vascular resistance (CVR) increased by 55% following a 36% decrease in cerebral oxygen consumption which was associated with a decrease in neuronal activity in the EEG. Hyperventilation led to a 25% further decrease in CBF due to a 43% increase in CVR while cerebral oxygen consumption remained unchanged. Hypoventilation was followed by a 67% increase in CBF and a 44% decrease in CVR cerebral oxygen consumption was decreased by 38%. This study shows that the reactivity of the cerebral vessels to changes in paCO2 is well maintained under Disoprivan.     

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

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

Effects of sevoflurane on cerebral blood flow and cerebral metabolic rate of oxygen in human beings: a comparison with isoflurane

BACKGROUND AND OBJECTIVE: Isoflurane is commonly used for neurosurgery but the effects of sevoflurane on human cerebral blood flow and cerebral metabolic rate of oxygen have not been fully evaluated. We therefore assessed the effects of sevoflurane and isoflurane on global cerebral blood flow and cerebral metabolic rate of oxygen in patients without noxious stimuli or neurological disorders. METHODS: General anaesthesia was induced with midazolam (0.2 mg kg(-1)) and fentanyl (5 microg kg(-1)) in 20 ASA I patients undergoing knee joint endoscopic surgery. Epidural anaesthesia was also performed to avoid noxious stimuli during surgery. Cerebral blood flow and cerebral arteriovenous oxygen content difference was measured using the Kety-Schmidt method with 15% nitrous oxide as a tracer before and after administration of either sevoflurane or isoflurane (1.5 minimum alveolar concentration, 60 min) and cerebral metabolic rate of oxygen was then calculated. RESULTS: Sevoflurane and isoflurane both increased cerebral blood flow (17%, P < 0.05; 25%, P < 0.05, respectively) and decreased cerebral metabolic rate of oxygen (26%, P < 0.01; 38%, P < 0.01, respectively). There were no significant differences in cerebral blood flow and cerebral metabolic rate of oxygen between sevoflurane and isoflurane. CONCLUSIONS: Sevoflurane and isoflurane similarly increased cerebral blood flow and decreased cerebral metabolic rate of oxygen in human beings anaesthetized with midazolam and fentanyl.     

Optimal perfusion flow rate for the brain during deep hypothermic cardiopulmonary bypass at 20 degrees C. An experimental study

The relationship between the perfusion flow rate and cerebral oxygen consumption during deep hypothermic cardiopulmonary bypass at 20 degrees C was investigated in dogs. In 10 dogs the perfusion flow rate was decreased in steps from 100 to 60, 30, and 15 ml/kg/min every 30 minutes. Although cerebral blood flow decreased as perfusion flow rate decreased, the ratio of cerebral blood flow to the perfusion flow rate increased significantly (p less than 0.05) at a perfusion flow rate of 15 ml/kg/min compared to that at a perfusion flow rate of 100 or 60 ml/kg/min. The arterial-sagittal sinus blood oxygen content difference increased as perfusion flow rate decreased. Consequently, cerebral oxygen consumption did not vary significantly at perfusion flow rates of 100 (0.48 +/- 0.10), 60 (0.43 +/- 0.14), and 30 ml/kg/min (0.44 +/- 0.12 ml/100 gm/min), and it decreased significantly to 0.31 +/- 0.22 ml/100 gm/min at a perfusion flow rate of 15 ml/kg/min. In five dogs the perfusion flow rate was decreased in one step from 100 to 15 ml/kg/min, and after 60 minutes' perfusion at a perfusion flow rate of 15 ml/kg/min, the perfusion flow rate was returned to 100 ml/kg/min. Cerebral oxygen consumption decreased significantly during 60 minutes' perfusion at a perfusion flow rate of 15 ml/kg/min and did not return to its initial value after the perfusion flow rate was returned to 100 ml/kg/min. These data indicate that the optimal perfusion flow rate for the brain during deep hypothermic cardiopulmonary bypass at 20 degrees C appears to be 30 ml/kg/min, with a possible oxygen debt in the brain resulting in anaerobic metabolism if the perfusion flow rate is kept at 15 ml/kg/min or less.     

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.     

Brain microvascular function during cardiopulmonary bypass

Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.     

The influence of pancuronium and vecuronium combined with balanced anaesthesia on haemodynamics and myocardial oxygen balance

The effects of the non-depolarizing muscle relaxants pancuronium (Pancuronium) and vecuronium (Norcuron) (0.1 mg/kg) on myocardial blood flow, myocardial oxygen consumption, myocardial lactate balance, cardiovascular dynamics and electrocardiogram were studied in two groups of eight patients undergoing coronary artery bypass surgery. After induction of anaesthesia with 0.015-0.02 mg/kg flunitrazepam, isoflurane (0.5 vol%) and N2O/O2 (l/l), neuromuscular blockade was induced with pancuronium or vecuronium (0.1 mg/kg) combined with a single dose of 0.005 mg/kg fentanyl. Haemodynamic measurements were performed and the electrocardiogram was recorded before anaesthesia, in steady-state anaesthesia, after relaxation with pancuronium or vecuronium combined with fentanyl, and after intubation. The haemodynamic data consisted of heart rate, cardiac index, stroke volume index, mean arterial pressure, total peripheral resistance, pulmonary arterial pressure, pulmonary capillary wedge pressure, right atrial pressure, myocardial blood flow, coronary vascular resistance, myocardial oxygen consumption, coronary aterio-mixed venous content difference, myocardial lactate extraction and rate pressure product. In the vecuronium group, heart rate decreased significantly more (21%) than in the pancuronium group (9%). Therefore myocardial oxygen consumption (48% resp. 35%) and coronary blood flow (31% resp. 18%) decreased more in the vecuronium than in the pancuronium group. The higher metabolic demand in the pancuronium group induced a significantly lower coronary vascular resistance, because the decrease in coronary perfusion pressure was similar in both groups. None of the other haemodynamic parameters differed significantly in either patient group. We did not observe ST-segment depressions or elevations in the ECG, increases in PCWP or myocardial lactate production. Therefore extended myocardial ischaemia can be excluded in our patients who received pancuronium or vecuronium for neuromuscular blockade.     

Effects of temperature and flow rate on regional blood flow and metabolism during cardiopulmonary bypass.

Eleven dogs were subjected to a 150-minute period of cardiopulmonary bypass that consisted of a high-flow, normothermic phase, a high-flow, hypothermic phase, a low-flow, hypothermic phase, and then a high-flow, rewarming phase. Regional blood flow and oxygen consumption to the brain, intestines, kidney, and hind limb were determined at baseline and at 10-minute intervals during cardiopulmonary bypass. Blood flow to the carotid artery, superior mesenteric artery, and renal artery declined significantly with hypothermic cardiopulmonary bypass whereas blood flow to the femoral artery increased significantly. Although total body oxygen consumption returned to baseline values at the end of the rewarming phase, oxygen consumption for these regions differed somewhat from their baseline values. We conclude that blood flow during hypothermic cardiopulmonary bypass is shunted to skeletal muscle, particularly with high pump flows. Additionally, the return of total body oxygen consumption to baseline after rewarming is not necessarily reflected at the regional level.     

The influence of pH strategy on cerebral and collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease: results of a randomized trial and real-time monitoring

OBJECTIVE: The optimal pH strategy during hypothermic cardiopulmonary bypass remains controversial. Systemic pulmonary collateral circulation may develop in patients with cyanotic anomalies. The purpose of this study was to evaluate the effect of pH strategies on cerebral oxygenation and systemic pulmonary collateral circulation during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. METHODS: Forty cyanotic patients (age > 1 year) with heart disease were prospectively randomized into 2 groups. Group 1 (n = 19, 14.3 +/- 1.5 kg) underwent hypothermic cardiopulmonary bypass with alpha-stat strategy and group 2 (n = 21, 12.5 +/- 0.9 kg) with pH-stat. Cardiopulmonary bypass was established with pump-assisted drainage. Cerebral oxygenation was assessed by near-infrared spectroscopy and the systemic pulmonary collateral circulation was calculated by pump flows [% systemic pulmonary collateral circulation = perfusion flow - drainage flow)/perfusion flow x 100]. Lactate was measured as an index of systemic anaerobic metabolism. RESULTS: There were no significant differences in preoperative hematocrit, oxygen saturation, Qp/Qs, cardiopulmonary bypass duration, minimum temperatures, perfusion flow and pressure, urine output, and depth of anesthesia between the groups. Oxyhemoglobin signal and tissue oxygenation index of near-infrared spectroscopy monitoring were significantly lower in group 1 compared with group 2 (P =.008 and P <.0001, respectively), suggesting inadequate cerebral oxygenation with alpha-stat. Deoxygenated hemoglobin signal was significantly higher in group 1 relative to group 2 (P <.0001). The % systemic pulmonary collateral circulation was significantly lower in group 2 compared with group 1, suggesting a reduced pulmonary collateral circulation with pH-stat (P <.0001, average; group 1, 20.1% +/- 1.2%; group 2; 7.7% +/- 0.7%). Serum lactate was significantly lower in group 2 (P <.0001). CONCLUSIONS: The pH-stat strategy results in an improved environment, including sufficient cerebral oxygenation, decreased systemic pulmonary collateral circulation, and lower lactate level during hypothermic cardiopulmonary bypass in cyanotic patients with heart disease. Future studies should investigate the long-term neurological outcome.     

Preservation of static and dynamic cerebral autoregulation after mild hypothermic cardiopulmonary bypass

Background. Dysfunction of cerebral autoregulation might contributeto neurological morbidity after cardiac surgery. In this study,our aim was to assess the preservation of cerebral autoregulationafter cardiac surgery involving cardiopulmonary bypass (CPB). Methods. Dynamic and static components of cerebral autoregulationwere evaluated in 12 patients undergoing coronary artery bypassgraft surgery, anaesthetized with midazolam, fentanyl, and propofol,and using mild hypothermic CPB (31–33°C). Arterialpressure (ABP), central venous pressure (CVP), and blood flowvelocity in the middle cerebral artery (CBFV) were recorded.The cerebral perfusion pressure (CPP) was calculated as a differencebetween mean ABP and CVP. Rapid decrease of CPP was caused bya sudden change of patients' position from Trendelenburg toreverse Trendelenburg. Cerebral vascular resistance (CVR) wascalculated by dividing CPP by CBFV. Index of static cerebralautoregulation (CAstat) was calculated as the change of CVRrelated to change of CPP during the manoeuvre. Dynamic rateof autoregulation (RoRdyn) was determined as the change in CVRper second during the first 4 s immediately after a decreasein CPP, related to the change of CPP. Measurements were obtainedafter induction of anaesthesia, and 15, 30, and 45 min aftertermination of CPB. Results. No significant changes were found in CAstat or RoRdynafter CPB. Significant changes in CVR could be explained byconcomitant changes in body temperature and haematocrit. Conclusion. Autoregulation of cerebral blood flow remains preservedafter mild hypothermic CPB.      

Cerebral blood flow and metabolism during cardiopulmonary bypass with special reference to effects of hypotension induced by prostacyclin

Cerebral blood flow and metabolism of oxygen, glucose, and lactate were studied in 43 patients undergoing aortocoronary bypass. Twenty-five patients received prostacyclin infusion, 50 ng per kilogram of body weight per minute, during cardiopulmonary bypass (CPB), and 18 patients served as a control group. Regional cerebral blood flow (CBF) was studied by intraarterially injected xenon 133 and a single scintillation detector. Oxygen tension, carbon dioxide tension, oxygen saturation, glucose, and lactate were measured in arterial and cerebral venous blood. Mean arterial blood pressure decreased during hypothermia and prostacyclin infusion to less than 30 mm Hg. The regional CBF was, on average, 22 (standard deviation [SD] 4) ml/100 gm/min before CPB. It increased in the control group during hypothermia to 34 (SD 12) ml/100 gm/min, but decreased in the prostacyclin group to 15 (SD 5) ml/100 gm/min. It increased during rewarming in the prostacyclin group. After CPB, regional CBF was about 40 ml/100 gm/min in both groups. The cerebral arteriovenous oxygen pressure difference decreased more in the control group than in the prostacyclin group during hypothermia. The cerebral metabolic rate of oxygen decreased in both groups from approximately 2 ml/100 gm/min to about 1 ml/100 gm/min during hypothermia, increased again during rewarming, and after CPB was at the levels measured before bypass in both groups. There was no difference between the groups in regard to glucose and lactate metabolism.     

Surgical Stimulation during High-Dose Fentanyl Anaesthesia: Effects of Dehydrobenzperidol on the Haemodynamics and Myocardial Oxygenation

Twenty-four patients undergoing a coronary artery bypass grafting operation with high-dose fentanyl (100 micrograms/kg)-lorazepam-oxygen anaesthesia were divided into a control group and a group receiving in addition 0.25 mg/kg dehydrobenzperidol (DHBP) before the skin incision (DHBP-group). The changes in the central and coronary haemodynamics and the myocardial oxygenation were studied and compared between the two groups during the skin incision and sternotomy, in order to evaluate the possible effects of the dehydrobenzperidol in preventing the harmful haemodynamic effects of surgical stimulation during high-dose fentanyl anaesthesia. In the control group a marked increase in the systemic vascular resistance and mean arterial pressure was seen during surgery. This haemodynamic stimulation was prevented by dehydrobenzperidol during the skin incision and markedly reduced during the sternotomy. Regardless of whether or not DHBP was given, a significant increase in the myocardial oxygen consumption was observed during the sternotomy; in the control group, the increase was slightly higher and was compensated by a greater increase in the myocardial oxygen extraction. No significant changes were seen in the coronary sinus blood flow or coronary vascular resistance in either group during the study period. The surgery caused no change in the myocardial lactate extraction in either group, although myocardial lactate production was observed in one control patient and the myocardial lactate extraction was markedly reduced in two other control patients and one DHBP patient.     

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.     

Insulin-like growth factor 1 improves the relationship between systemic oxygen consumption and delivery in piglets after cardiopulmonary bypass

OBJECTIVE: We sought to assess the effects of insulin-like growth factor 1 on the balance between systemic oxygen consumption and oxygen delivery after cardiopulmonary bypass in piglets. METHODS: Twelve piglets weighing 4.5 to 8.3 kg undergoing hypothermic (28 degrees C) cardiopulmonary bypass for 70 to 120 minutes with 40 minutes of aortic crossclamping were studied before and during the first 6 hours after cardiopulmonary bypass. Oxygen consumption was continuously measured by an indirect calorimeter, Deltatrac II MBM-200 Metabolic Monitor (Datex Division Instrumentarium, Helsinki, Finland). Oxygen delivery and cardiac output were calculated from oxygen consumption and the arterial and mixed venous oxygen contents sampled before and every 30 minutes after cardiopulmonary bypass. Oxygen extraction ratio was derived by the ratio of oxygen consumption to oxygen delivery. Arterial blood lactate was measured before and every 30 minutes after cardiopulmonary bypass. Six animals were randomly assigned to receive an intravenous infusion of insulinlike growth factor 1 at 1.2 mg/h from 1 to 6 hours after cardiopulmonary bypass; the remaining 6 served as a control group. RESULTS: Relative to the control group, intravenous infusion of insulin-like growth factor 1 significantly reduced oxygen consumption (P =.02) and increased cardiac output (P =.016) and oxygen delivery (P =.049) during the first 6 hours after surgery with hypothermic cardiopulmonary bypass. As a result, oxygen extraction was significantly decreased (P =.012). CONCLUSIONS: Intravenous infusion of insulin-like growth factor 1 improved oxygen transport by reducing oxygen consumption as well as increasing cardiac output and oxygen delivery during the first 6 hours after cardiopulmonary bypass in piglets. This may have important clinical implications for the care of critically ill children after surgery with cardiopulmonary bypass.