Cerebral blood flow and metabolism in patients undergoing anesthesia for carotid endarterectomy. A comparison of isoflurane, halothane, and fentanyl

The effects of isoflurane, halothane, and fentanyl on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) during anesthesia prior to carotid endarterectomy were compared using the intravenous method of 133-Xenon CBF determination. Patients, mean (+/- SE) age 68 +/- 2, received either isoflurane (N = 16), 0.75% in O2 and N2O, 50:50; halothane (N = 11), 0.5% in O2 and N2O, 50:50; or fentanyl (N = 10), 5-6 micrograms/kg bolus and then 1-2 micrograms.kg-1.h-1 infusion in addition to O2 and N2O, 40:60. Measurements were made immediately before carotid occlusion. Mean (+/- SE) CBF (ml.100 g-1.min-1) was 23.9 +/- 2.1 for isoflurane, 33.8 +/- 4.8 for halothane, and 19.3 +/- 2.4 for fentanyl. CMRO2 (ml.100 g-1.min-1) was available from 22 patients and was 1.51 +/- 0.28 for isoflurane (N = 7), 1.45 +/- 0.24 for halothane (N = 6), and 1.49 +/- 0.21 for fentanyl (N = 9). Although CBF was greater during halothane than during isoflurane or fentanyl anesthesia (p less than 0.05), there were no demonstrable differences in CMRO2 among the 3 agents. We conclude that choice of anesthetic agent for cerebrovascular surgery with comparable anesthetic regimens should not be made on the basis of "metabolic suppression." During relatively light levels of anesthesia, vasoactive properties of anesthetics are more important than cerebral metabolic depression with respect to effects on the cerebral circulation.     

A comparison of the direct cerebral vasodilating potencies of halothane and isoflurane in the New Zealand white rabbit

Halothane is commonly viewed as a more potent cerebral vasodilator than isoflurane. It was speculated that the lesser vasodilation caused by isoflurane might be the result of the greater reduction in cerebral metabolic rate (CMR) that it causes, and that the relative vasodilating potencies of halothane and isoflurane would be similar if the two agents were administered in a situation that precluded volatile-agent-induced depression of CMR. To test this hypothesis, cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) were measured in two groups of rabbits before and after the administration of 0.75 MAC halothane or isoflurane. One group received a background anesthetic of morphine and N2O, which resulted in an initial CMRO2 of 3.21 +/- 0.17 (SEM) ml X 100 g-1 X min-1; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMRO2 of 1.76 +/- 0.16 ml X 100 g-1 X min-1. In rabbits receiving a background of morphine sulfate/N2O, halothane resulted in a significantly greater CBF (65 +/- 10 ml X 100 g-1 X min-1) than did isoflurane (40 +/- 5 ml X 100 g-1 X min-1). Both agents caused a reduction in CMRO2, but CMRO2 was significantly less during isoflurane administration. By contrast, with a background of pentobarbital anesthesia, CBF increased by significant and similar amounts with both halothane and isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of isoflurane on cerebral blood flow and metabolism in humans during craniotomy for small supratentorial cerebral tumors

Fourteen patients were studied during craniotomy for small supratentorial cerebral tumors. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice by a modification of the Kety-Schmidt technique using 133Xe intravenously. Anesthesia was induced with thiopental 5-7 mg X kg-1, fentanyl 0.2 mg, and pancuronium, and maintained with 0.75% inspired isoflurane concentration in 67% nitrous oxide, and moderate hypocapnia. In one group of patients (n = 7), the inspired isoflurane concentration was maintained at 0.75% throughout anesthesia. One hour after induction of anesthesia, CBF and CMRO2 averaged 31 +/- 3 ml X 100 g-1 X min-1 and 2.1 +/- 0.2 ml O2 X 100 g-1 X min-1 (X +/- SEM), respectively. During repeat studies 1 h later, CBF and CMRO2 were unchanged. In a second group of patients (n = 7), an increase in the inspired isoflurane concentration from 0.75% to 1.5% was associated with a significant decrease in CMRO2 from 2.4 +/- 0.1 to 1.9 +/- 0.1 ml O2 X 100 g-1 X min-1, and no change in CBF. It is concluded that this anesthetic regimen is safe to use in patients with small supratentorial tumors in whom only a small midline shift has occurred.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2-reactivity during craniotomy for supratentorial cerebral tumours in halothane anaesthesia. A dose-response study

Fourteen patients were studied during craniotomy for small supratentorial cerebral tumours. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice by a modification of the Kety-Schmidt technique using 133Xe intravenously. Anaesthesia was induced with thiopental 4-6 mg kg-1, fentanyl and pancuronium, and maintained with an inspiratory halothane concentration of 0.45% in nitrous oxide 67% at a moderate hypocapnic level. In one group of patients (n = 7) the inspiratory halothane concentration was maintained at 0.45% throughout anaesthesia. About 1 h after induction of anaesthesia CBF and CMRO2 averaged 35 +/- 2 ml 100 g-1 min-1 and 2.7 +/- 0.3 ml O2 100 g-1 min-1 (mean +/- s.c. mean), respectively. During repeat studies 1 h later CBF and CMRO2 did not change. In another group of patients (n = 7) an increase in halothane concentration from 0.45% to 0.90% was associated with a significant decrease in CMRO2 from 2.3 +/- 0.1 to 2.0 +/- 0.1 ml O2 100 g-1 min-1. The CO2-reactivity measured after the second flow measurement was preserved. It is concluded that halothane in this study induces a dose-dependent decrease in cerebral metabolism, an increase in CBF while CO2-reactivity is maintained.     

The detrimental effect of lidocaine on cerebral metabolism measured in dogs anesthetized with isoflurane

Previous studies in dogs have demonstrated that massive doses of intravenous lidocaine (160 mg X kg-1) can inhibit cerebral oxygen metabolism to a greater degree when administered with pentobarbital than can pentobarbital alone. From these data, it was hypothesized that lidocaine decreases cerebral metabolism by two means: suppression of cortical electrical activity and stabilization of neuronal membranes, and it was suggested that lidocaine might provide protection for the ischemic brain. In an attempt to apply this property clinically, the effect of a lower, clinically tolerated dose of lidocaine (15 mg X kg-1) on cerebral oxygen metabolism and cerebral blood flow was examined in dogs receiving deep isoflurane anesthesia. Once maximal metabolic suppression, as reflected by an isoelectric EEG, was achieved with isoflurane (3% end-expired), the administration of this dose of lidocaine had little effect on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2). The CBF was 94 +/- 19 ml X min-1 X 100 g-1 during 3% isoflurane anesthesia, and was 102 +/- 11 ml X min-1 X 100 g-1 with the addition of lidocaine. The CMRO2 was 2.32 +/- 0.23 ml X min-1 X 100 g-1 during isoflurane anesthesia, and was 2.18 +/- 0.09 ml X min-1 X 100 g-1 following the administration of lidocaine. However, this dose of lidocaine did produce a derangement of cerebral metabolites. The cerebral concentration of ATP during 3% isoflurane anesthesia was 2.07 +/- 0.04 mumol X g-1 (cerebral ATP in normal unanesthetized dogs is 2.01 +/- 0.01 mumol X g-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of nitrous oxide on cortical cerebral blood flow during anesthesia with halothane and isoflurane, with and without morphine, in the rabbit

The effect of nitrous oxide on cortical cerebral blood flow (CBF) was examined during a varying background anesthetic state in the New Zealand White rabbit. Seventy percent nitrous oxide resulted in significant and similar increases in CBF during anesthesia with both 0.5 MAC of halothane (44 +/- 14 to 63 +/- 17 ml.100 g-1.min-1) (mean +/- SD) and anesthesia with isoflurane (34 +/- 9 to 41 +/- 11 ml.100 g-1.min-1). During anesthesia with 1.0 MAC halothane or isoflurane, N2O also increased CBF, but the increments (halothane, 73 +/- 34 to 111 +/- 54 ml.100 g-1 min-1; isoflurane 34 +/- 13 to 69 +/- 34 ml.100 g-1.min-1) were significantly greater than those observed at 0.5 MAC. When 0.5 MAC halothane or isoflurane was supplemented with morphine (10 mg/kg followed by an infusion of 2 mg.kg-1.min-1), the CBF effect of N2O was not significantly different from that observed with 0.5 MAC alone. It was concluded that, in the rabbit, the effects of N2O on cortical CBF vary with the background anesthetic state and that the increase in CBF caused by N2O becomes greater as the end-tidal concentration of halothane or isoflurane increases from 0.5 to 1.0 MAC. Morphine, when added to 0.5 MAC of halothane or isoflurane, does not alter the effect of 70% N2O on cortical CBF.     

The effect of isoflurane-induced hypotension on cerebral blood flow and cerebral metabolic rate for oxygen in humans

Deliberate hypotension was induced with isoflurane (mean inspired concentration 2.3 +/- 1.0%) in 12 patients undergoing craniotomy for clipping of cerebral aneurysms. Global cerebral blood flow (CBF) was measured before, during, and after hypotension. Arterio-venous O2 content difference was measured concomitantly, and the cerebral metabolic rate for oxygen (CMRO2) was calculated from these data. Mean arterial pressure (MAP) was reduced from 78 +/- 5 mmHg to 51 +/- 7 mmHg and then returned to 82 +/- 8 mmHg. Mean CBF before hypotension was 49 +/- 14 ml X 100 g-1 X min-1 and was unchanged during (45 +/- 12 ml X 100 g-1 X min-1) and after (49 +/- 15 ml X 100 g-1 X min-1) hypotension. The CMRO2 before hypotension was 2.0 +/- 0.6 ml X 100 g-1 X min-1. This was statistically significantly (P less than 0.025) reduced to 1.5 +/- 0.5 ml X 100 g-1 X min-1 during hypotension and then returned to 2.2 +/- 0.6 ml X 100 g-1 X min-1 on return to normotension. This indicates that the global cerebral O2 supply-demand balance was favorably influenced by isoflurane. No complications could be attributed to the hypotensive technique. We conclude that, with regard to global cerebral oxygenation, isoflurane is a safe agent with which to induce hypotension during neurosurgery.     

Correlation of regional cerebral blood flow (rCBF) with EEG changes during isoflurane anesthesia for carotid endarterectomy: critical rCBF

A prospective evaluation of regional cerebral blood flow (rCBF) (ipsilateral middle cerebral artery distribution) was determined using a 133Xe clearance technique in 31 ASA P.S. II-III patients anesthetized with isoflurane-50% N2O in O2 for carotid endarterectomy. Each patient was monitored with 16-channel EEG throughout anesthesia and surgery. Critical rCBF was defined as that flow below which EEG signs of ischemia occurred. Critical rCBF (T1/2 method of analysis) was less than 10 ml X 100 g-1 X min-1 (mean +/- SE 5.9 +/- 1.2) in the six patients in whom transient EEG changes occurred at the time of temporary surgical carotid artery occlusion. No EEG changes occurred with occlusion in the other 25 patients; mean (+/- SE) occlusion rCBF in this group was 18.9 +/- 1.3 ml X 100 g-1 X min-1 (P less than 0.001). Preocclusion flows were not significantly different in the two groups. Critical rCBF during isoflurane anesthesia was less than that previously determined during halothane anesthesia (18-20 ml X 100 g-1 X min-1), and is compatible with the effects of isoflurane on CMRO2 and CBF.     

A comparison of cerebral ischemic flow thresholds during halothane/N2O and isoflurane/N2O anesthesia in rats.

Isoflurane/N2O anesthesia has been reported to reduce the cerebral blood flow (CBF) threshold at which electroencephalographic changes occur in humans during carotid occlusion (when compared to halothane/N2O). To further evaluate this observation, normocapnic, normothermic rats were anesthetized with 0.75 MAC isoflurane or halothane in combination with 60% N2O. The electrocorticogram (ECoG) and the cortical DC potential were recorded using glass microelectrodes. Both carotid arteries were occluded, and mean arterial pressure (MAP) was reduced over 3-5 min (by phlebotomy) to predetermined values between 30 and 75 mmHg. This MAP was maintained for 10 min, and CBF was then measured in cortical gray matter using [3H]-nicotine. Flows were then correlated with ECoG changes and with the presence or absence of cortical depolarization (which reflects the loss of transmembrane ion homeostasis). In other rats, the cortical cerebral metabolic rate for glucose (CMRglu) was determined autoradiographically using [14C]-deoxyglucose. Finally, the time to depolarization was determined in rats killed with KCl and in rats subjected to hypotension (MAP = 30-35 mmHg) followed by abrupt bilateral carotid occlusion. The distributions of CBF values in the anesthetic groups were essentially identical. The incidence of either major ECoG changes or isoelectricity did not differ between anesthetics. The CBF associated with major ECoG changes (excluding isoelectricity) were 35 +/- 12 and 39 +/- 18 ml.100 g-1.min-1 in the halothane/N2O and isoflurane/N2O groups respectively (mean +/- SD, difference not significant [NS]). Isoelectricity was seen at 7 +/- 4 ml.100 g-1.min-1 (median = 6.5) with halothane/N2O and 17 +/- 19 ml.100 g-1.min-1 (median = 11) with isoflurane/N2O (again, NS). The incidence of sustained depolarization did not differ between anesthetics (9 of 25 for halothane/N2O, 8 of 24 with isoflurane/N2O). CBF associated with sustained depolarization was 13 +/- 12 ml.100 g-1.min-1 (median = 10) with halothane/N2O, compared with 9 +/- 6 ml.100 g-1.min-1 (median = 9) for isoflurane/N2O (NS). In rats subjected to cardiac arrest, the time to depolarization was longer with isoflurane/N2O (102 +/- 19 s vs. 77 +/- 7 s). In rats subjected to carotid occlusion at a MAP = 30-35 mmHg, the time to depolarization was again longer with isoflurane/N2O (210 +/- 78 s vs. 122 +/- 44 s). Cortical CMRglu was lower with isoflurane/N2O (25 +/- 5 mumol.100 g-1.min-1) than with halothane (43 +/- 13 mumol.100 g-1.min-1, P = 0.03). The results indicate that isoflurane/N2O anesthesia delays the onset of ischemic cell depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of sufentanil on cerebral metabolism and circulation in the rat

The authors examined the effects of large intravenous doses of sufentanil (5-160 micrograms/kg) on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in rats. CBF and CMRO2 were measured by a modified Kety-Schmidt technique using 133Xenon washout. Progressive decreases in CBF and CMRO2 occurred in animals receiving sufentanil. The maximum decrease was 53% and 40% for CBF and CMRO2 respectively, at a dose of 80 micrograms/kg. The values for CBF and CMRO2 in this group were 105 +/- 10 ml X 100 g-1 X min-1 (mean +/- SEM) and 6.5 +/- 0.5 ml X 100 g-1 X min-1, respectively, compared with 226 +/- 28 ml X 100 g-1 X min-1 and 10.9 +/- 1 ml X 100 g-1 X min-1 in the control group, which received N2O 70% in oxygen. Larger doses of sufentanil did not cause further significant changes in CBF and CMRO2. Sharp waves appeared on the electroencephalogram (EEG) of all the animals following sufentanil injection, and some animals had EEG changes develop consistent with seizure activity. This seizure-like activity appeared to consist of a single episode of short duration in the groups receiving 5, 10, and 20 micrograms/kg sufentanil. The incidence and frequency of seizure activity increased in the groups receiving higher doses of sufentanil, although the duration of seizures was still short. The results of this study indicate that sufentanil causes a significant decrease in CBF and CMRO2 similar to that previously reported for fentanyl, and high doses of sufentanil may cause frequent seizure-like patterns appearing on EEG.     

CBF and CMRO2 during Continuous Etomidate Infusion Supplemented with N2O and Fentanyl in Patients with Supratentorial Cerebral Tumour. A Dose-Response Study

In 14 patients with supratentorial cerebral tumours with midline shift below 10 mm, CBF and CMRO2 were measured (Kety & Schmidt) during craniotomy. The anaesthesia was continuous etomidate infusion supplemented with nitrous oxide and fentanyl. The patients were divided into two groups. In Group 1 etomidate infusion of 30 micrograms kg-1 min-1 was used throughout the anaesthesia, and CBF and CMRO2 were measured twice. In this group CMRO2 (means +/- s.d.) averaged 2.31 +/- 0.43 ml O2 100 g-1 min-1 70 min after induction and 2.21 +/- 0.38 ml O2 100 g-1 min-1 130 min after induction. In Group 2 the etomidate infusion was increased from 30 to 60 micrograms kg-1 min-1 after the first study and a significant fall in CMRO2 from 2.52 +/- 0.56 to 1.76 +/- 0.40 ml O2 100 g-1 min-1 was found. Simultaneously, a significant fall in CBF was observed. The CO2 reactivity was preserved during anaesthesia.     

The response of the feline cerebral circulation to PaCO2 during anesthesia with isoflurane and halothane and during sedation with nitrous oxide

The reduction in cerebral blood flow (CBF) caused by hypocapnia is an important element of neuroanesthetic techniques. While it has been demonstrated previously that the CO2 response of the cerebral circulation (CO2 X R) is enhanced (i.e., greater delta CBF/delta PaCO2) during halothane administration, the effect of isoflurane on CO2 X R has not been evaluated completely. Accordingly, the authors examined CO2 X R in cats during anesthesia with 1.0 MAC isoflurane (with 75% N2O) and compared it with CO2 X R during anesthesia with 1.0 MAC halothane (with 75% N2O) and with CO2 X R during the administration of 75% N2O alone. CO2 X R during anesthesia with isoflurane-N2O was enhanced relative to that observed during administration of both halothane-N2O (P less than 0.025) and N2O alone (P less than .001). CO2 X R during anesthesia with halothane-N2O was, in turn, greater than that observed during the administration of N2O alone (P less than 0.025). Furthermore, at similar levels of hypocapnia (PaCO2 18-20 mmHg), CBF was significantly lower (P less than 0.01) during administration of isoflurane-N2O (29.0 +/- 4.5 ml X 100 g-1 X min-1) than during administration of either N2O (40.6 +/- 5.5 ml X 100 g-1 X min-1) or halothane-N2O (39.6 +/- 7.8 ml X 100 g-1 X min-1). CBF values during administration of the N2O alone and halothane-N2O were not different during hypocapnia.(ABSTRACT TRUNCATED AT 250 WORDS)     

CBF and CMRo2 during craniotomy for small supratentorial cerebral tumours in enflurane anaesthesia. A dose-response study

In 14 patients with supratentorial cerebral tumours with midline shift less than or equal to 10 mm, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice on the contralateral side of the craniotomy, using a modification of the Kety & Schmidt method. For induction of anaesthesia, thiopental, fentanyl and pancuronium were used. The anaesthesia was maintained with enflurane 1% in nitrous oxide 67%. Moderate hypocapnia to a level averaging 4.3 kPa was achieved. The patients were divided into two groups. In Group 1 (n = 7), 1% enflurane was used throughout the anaesthesia, and CBF and CMRO2 measured about 70 min after induction averaged 30.1 ml 100 g-1 min-1 and 1.98 ml O2 100 g-1 min-1, respectively. During the second CBF study 1 h later, CBF and CMRO2 were unchanged (P greater than 0.05). In Group 2 (n = 7), the inspiratory enflurane concentration was increased from 1 to 2% after the first CBF measurement. In this group a significant decrease in CMRO2 was observed, while CBF was unchanged. In six patients EEG was recorded simultaneously with the CBF measurements. In patients subjected to increasing enflurane concentration (Group 2), a suppression in the EEG activity was observed without spike waves. It is concluded that enflurane induces a dose-related decrease in CMRO2 and suppression in the EEG activity, whereas CBF was unchanged.     

Isoflurane when compared to enflurane and halothane decreases the frequency of cerebral ischemia during carotid endarterectomy

Data from the records of patients who underwent 2223 carotid endarterectomies at the Mayo Clinic between January 1, 1972, and December 31, 1985, were abstracted to compare the effects of isoflurane, enflurane, and halothane on the critical cerebral blood flow (CBF) (i.e., the CBF below which the majority of patients develop EEG ischemic changes within 3 min of carotid occlusion), the incidence of EEG ischemic changes, and the neurologic outcome. In a total of 2196 of these procedures, the patient received one of the three volatile anesthetics and, in 2010 of these, both the EEG and the CBF were monitored. Chronologically, halothane was the primary agent from 1972-1974; enflurane progressively replaced halothane during 1975-1981; and isoflurane was used almost exclusively since 1982. This analysis confirmed a previous study that the critical CBF during isoflurane anesthesia (703 procedures) was approximately 10 ml X 100 g-1 X min-1, as contrasted to that of approximately 20 ml X 100 g-1 X min-1 during halothane anesthesia (467 procedures). This analysis also established that the critical CBF during enflurane anesthesia (840 procedures) was approximately 15 ml X 100 g-1 X min-1. The incidence of EEG ischemic changes was significantly less (P less than 0.001) during isoflurane anesthesia (18%) than during either enflurane (26%) or halothane (25%) anesthesia. This difference occurred despite the fact that the preoperative risk status was greater in the patients given isoflurane. There was no difference in neurologic outcome between the three anesthetics, and none was expected, since all patients with EEG changes were immediately shunted, if possible.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of halothane, isoflurane, and sevoflurane on the liver with hepatic artery ligation in the beagle.

Recently, there has been increasing interest in the alterations in splanchnic and hepatic circulation and preservation of hepatic oxygenation and function during anesthesia and surgery. However, the effects of volatile anesthetics under a condition of marginal hepatic oxygen supply are not well understood. Using a crossover design, we therefore studied the effects of equianesthetic concentrations (1.5 MAC) of halothane, isoflurane, and sevoflurane on hepatic oxygenation and function in nine beagles in which the hepatic artery had been ligated. Portal blood flow was measured by an electro-magnetic flow meter. Hepatic function was assessed by indocyanine green elimination kinetics. While cardiac output and mean arterial pressure were greater during halothane anesthesia than during isoflurane and sevoflurane anesthesia, portal blood flow and hepatic oxygen supply were significantly less during halothane and sevoflurane anesthesia than during isoflurane anesthesia. With regard to hepatic oxygen uptake, there was a significant difference between halothane (2.7 +/- 1.2 ml.min-1 x 100 g-1) and sevoflurane (3.7 +/- 2.0 ml.min-1 x 100 g-1; P less than 0.05). Consequently, the hepatic oxygen supply/uptake ratio and the hemoglobin oxygen saturation and oxygen partial pressure in hepatic venous blood during sevoflurane anesthesia were significantly less than they were with the other anesthetics. Indocyanine green clearance was better preserved during sevoflurane anesthesia (39.7 +/- 12.0 ml.min-1) than during halothane anesthesia (30.9 +/- 8.4 ml.min-1; P less than 0.05). We conclude that sevoflurane is accompanied by a smaller oxygen supply/uptake ratio than is halothane and isoflurane, while it preserves hepatic function.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of anesthetics and PaCO2 on the cerebrovascular, metabolic, and electroencephalographic responses to nitrous oxide in the rabbit

The effects of nitrous oxide (N2O) on cerebral blood flow and metabolism, intracranial pressure (ICP), the electroencephalogram etc. has been well described, at least when N2O is used alone. However, during neurosurgical procedures, N2O is almost always given in combination with either volatile or intravenous agents, and generally after the institution of some degree of hypocarbia. Unfortunately, the modifying influence of such interventions are not well known, and, therefore, the cerebral effects of 70% N2O were studied in rabbits anesthetized with either 1 MAC halothane or isoflurane, or with a fentanyl/pentobarbital combination, during both normocarbia (PaCO2 approximately 40 mm Hg) and hypocarbia (PaCO2 approximately 20 mm Hg). Cortical cerebral blood flow (CBFc) and sagittal sinus blood flow (CBFss--as an index of "global" forebrain flow) were measured using the hydrogen clearance method. Cerebral oxygen consumption (CMRO2) was calculated, and intracranial pressure (ICP), central venous pressure, heart rate, mean arterial pressure, and the EEG were also recorded. CBFc during normocarbic halothane, isoflurane, and fentanyl-pentobarbital anesthesia was 69 +/- 23, 41 +/- 16, 53 +/- 26 ml.100g-1.min-1 (mean +/- SD) respectively, with a significant difference between halothane and isoflurane. The addition of 70% N2O to all three anesthetics significantly increased CBFc by 32%, 34% and 36% respectively during normocarbia and by 47%, 65% and 27% during hypocarbia. A similar pattern was seen for CBFss. There were no significant differences in the response to N2O based either on anesthetic or PaCO2, except that the increase in CBFss produced by N2O during normocarbic fentanyl-pentobarbital anesthesia (10%) was less than that noted during normocarbic halothane anesthesia (39%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral functional, metabolic, and hemodynamic effects of etomidate in dogs

The effects of a continuous infusion of etomidate on cerebral function, metabolism, and hemodynamics and on the systemic circulation were examined in six dogs. The infusion rate of etomidate was progressively increased at 20-min intervals from 0.02 to 0.4 mg X kg-1 X min-1 for 2 h. Cerebral oxygen consumption (CMRO2) decreased until there was cessation of neuronal function as reflected by the onset of an isoelectric EEG. This occurred during an infusion of 0.3 mg X kg-1 X min-1 etomidate when the animals had received a total of 10.7 mg X kg-1 over 91 min. At this time the CMRO2 was 2.6 ml X min-1 X 100 g-1, 48% of control. Thereafter, despite continued administration of etomidate to a total dose of 21.4 mg X kg-1, CMRO2 did not decrease further. Cerebral blood flow (CBF) decreased in association with a marked increase in cerebrovascular resistance but was independent of changes in CMRO2. CBF decreased precipitously from 145 +/- 23 to 72 +/- 6 ml X min-1 X 100 g-1 during the lowest infusion rate of 0.02 mg X kg-1 X min-1 etomidate and stabilized at 34-36 ml X min-1 X 100 g-1 during an infusion rate of 0.1 mg X kg-1 X min-1. CBF remained at this level despite the continued administration of etomidate and a further decrease in CMRO2. Etomidate produced physiologically minor but statistically significant changes in the systemic hemodynamic variables. Assays of cerebral metabolites taken at the end of the infusion revealed a normal energy state and a very mild but significant increase in cerebral lactate to 1.49 mumol X g-1. We conclude that etomidate is a potent, direct cerebral vasoconstrictor that appears to be independent of its effect on CMRO2 and that the cerebral metabolic effects of etomidate are secondary to its effect on neuronal function, with little if any direct or toxic effects on metabolic pathways.     

A porcine model for sequential assessments of cerebral haemodynamics and metabolism

We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.     

A comparison of cerebral blood flow reactivity to CO2 during halothane versus isoflurane anesthesia for carotid endarterectomy

The effects of isoflurane or halothane on cerebral blood flow (CBF) reactivity to changes in arterial carbon dioxide tension (PaCO2) during carotid endarterectomy were compared using the intravenous method of 133Xe-CBF determination. Patients, aged 65 +/- 3 yr (mean +/- SE), received O2 and N2O (1:1) and either 0.75% isoflurane (n = 7) or 0.5% halothane (n = 7). Patient demographic and clinical data were similar for both groups and followed the expected strata of patients with ischemic cerebrovascular disease. Measurements were made during the period of temporary bypass shunting. In the isoflurane group, increasing PaCO2 from 33.3 +/- 1.4 to 43.4 +/- 1.3 mm Hg resulted in a significant (P less than 0.05) increase in CBF from 21 +/- 1 to 35 +/- 4 mL.100 g-1.min-1. In the halothane group, increasing PaCO2 from 31.1 +/- 1 to 39.4 +/- 1.6 mm Hg resulted in a significant increase in CBF from 26 +/- 3 to 37 +/- 3 mL.100 g-1.min-1. Mean CBF reactivity to changes in PaCO2 (mL.100 g-1.min-1.mm Hg-1) was 1.74 +/- 0.39 for isoflurane and 1.78 +/- 0.4 for halothane (not significant), corresponding to a relative change of 4.8% +/- 0.8% and 5.2% +/- 1.3% per mm Hg, respectively. There is no significant difference between halothane and isoflurane in their effects on CO2 reactivity in the mildly hypocapnic to normocapnic range.     

The response of the canine cerebral circulation to hyperventilation during anesthesia with desflurane

Arterial CO2 tension (PaCO2) is an important factor controlling cerebral blood flow (CBF) and cerebral vascular resistance (CVR) in animals and humans. The normal responsiveness of the cerebral vasculature to PaCO2 is approximately 2 ml.min-1.100 g-1.mmHg-1. This study examined the effect of desflurane, a new volatile anesthetic, on the responsiveness of the cerebral vasculature to changes in PaCO2. Mean arterial pressure (MAP), CBF, CVR, intracranial pressure (ICP), and cerebral metabolic rate for O2 (CMRO2) were measured in five dogs anesthetized with desflurane (0.5-1.5 MAC) at normocapnia (PaCO2 = 40 mmHg) and at two levels of hypocapnia (PaCO2 = approximately 30 and approximately 20 mmHg). Under desflurane anesthesia, similar changes in CBF and CVR occurred with hyperventilation at all MAC levels of desflurane. At 0.5 MAC, CBF decreased significantly, from 81 +/- 6 to 40 +/- 3 ml.min-1.100 g-1 (P less than 0.05, mean +/- SE) when PaCO2 was decreased from 40 to 24 mmHg; i.e., the CBF decreased approximately 2.6 ml.min-1.100 g-1.mmHg-1. At 1.0 MAC desflurane, CBF decreased significantly, from 79 +/- 10 to 43 +/- 5 ml.min-1.100 g-1 with hyperventilation (2.0 ml.min-1.100 g-1.mmHg-1); at 1.5 MAC desflurane, CBF decreased from 65 +/- 6 to 38 +/- 2 ml.min-1.100 g-1 with hyperventilation (1.6 ml.min-1.100 g-1.mmHg-1). Despite the significant decreases in CBF with hyperventilation, there was no significant change in ICP. Dose-dependent decreases in MAP were observed with increasing concentrations of desflurane but were not significantly affected by ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)