Effects of Sevoflurane, Propofol, and Adjunct Nitrous Oxide on Regional Cerebral Blood Flow, Oxygen Consumption, and Blood Volume in Humans

Background: Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography.

Methods: 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine rCBF, rCMRO2 and rCBV, respectively, in eight healthy male subjects during the awake state (baseline) and at four different anesthetic regimens: (1) sevoflurane alone, (2) sevoflurane plus 70% N2O (S+N), (3) propofol alone, and (4) propofol plus 70% N2O (P+N). Sevoflurane and propofol were titrated to keep a constant hypnotic depth (Bispectral Index 40) throughout anesthesia. End-tidal carbon dioxide was strictly kept at preinduction level.

Results: The mean +/- SD end-tidal concentration of sevoflurane was 1.5 +/- 0.3% during sevoflurane alone and 1.2 +/- 0.3% during S+N (P < 0.001). The measured propofol concentration was 3.7 +/- 0.7 [mu]g/ml during propofol alone and 3.5 +/- 0.7 [mu]g/ml during P+N (not significant). Sevoflurane alone decreased rCBF in some (to 73-80% of baseline, P < 0.01), and propofol in all brain structures (to 53-70%, P < 0.001). Only propofol reduced also rCBV (in the cortex and cerebellum to 83-86% of baseline, P < 0.05). Both sevoflurane and propofol similarly reduced rCMRO2 in all brain areas to 56-70% and 50-68% of baseline, respectively (P < 0.05). The adjunct N2O counteracted some of the rCMRO2 and rCBF reductions caused by drugs alone, and especially during S+N, a widespread reduction (P < 0.05 for all cortex and cerebellum vs. awake) in the oxygen extraction fraction was seen. Adding of N2O did not alter the rCBV effects of sevoflurane and propofol alone.     

Effects of subanesthetic doses of ketamine on regional cerebral blood flow,oxygen consumption,and blood volume in humans

BACKGROUND: Animal experiments have demonstrated neuroprotection by ketamine. However, because of its propensity to increase cerebral blood flow, metabolism, and intracranial pressure, its use in neurosurgery or trauma patients has been questioned. METHODS: 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine quantitative regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV), respectively, on selected regions of interest of nine healthy male volunteers at baseline and during three escalating concentrations of ketamine (targeted to 30, 100, and 300 ng/ml). In addition, voxel-based analysis for relative changes in rCBF and rCMRO2 was performed using statistical parametric mapping. RESULTS: The mean +/- SD measured ketamine serum concentrations were 37 +/- 8, 132 +/- 19, and 411 +/- 71 ng/ml. Mean arterial pressure was slightly elevated (maximally by 15.3%, P < 0.001) during ketamine infusion. Ketamine increased rCBF in a concentration-dependent manner. In the region-of-interest analysis, the greatest absolute changes were detected at the highest ketamine concentration level in the anterior cingulate (38.2% increase from baseline, P < 0.001), thalamus (28.5%, P < 0.001), putamen (26.8%, P < 0.001), and frontal cortex (25.4%, P < 0.001). Voxel-based analysis revealed marked relative rCBF increases in the anterior cingulate, frontal cortex, and insula. Although absolute rCMRO2 was not changed in the region-of-interest analysis, subtle relative increases in the frontal, parietal, and occipital cortices and decreases predominantly in the cerebellum were detected in the voxel-based analysis. rCBV increased only in the frontal cortex (4%, P = 0.022). CONCLUSIONS: Subanesthetic doses of ketamine induced a global increase in rCBF but no changes in rCMRO2. Consequently, the regional oxygen extraction fraction was decreased. Disturbed coupling of cerebral blood flow and metabolism is, however, considered unlikely because ketamine has been previously shown to increase cerebral glucose metabolism. Only a minor increase in rCBV was detected. Interestingly, the most profound changes in rCBF were observed in structures related to pain processing.     

A subanesthetic concentration of sevoflurane increases regional cerebral blood flow and regional cerebral blood volume and decreases regional mean transit time and regional cerebrovascular resistance in volunteers

Inhaled anesthetics exert metabolically mediated effects on cerebral blood vessels both directly and indirectly. We investigated the effects of a 0.4 minimum alveolar subanesthetic concentration of sevoflurane on regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), regional cerebrovascular resistance (rCVR), and regional mean transit time (rMTT) in volunteers by means of contrast-enhanced magnetic resonance imaging perfusion measurement. Sevoflurane increased rCBF by 16% to 55% (control, 55. 03 +/- 0.33 to 148.83 +/- 1.9 mL. 100 g(-1). min(-1); sevoflurane, 71.75 +/- 0.36 to 193.26 +/- 2.14 mL. 100 g(-1). min(-1)) and rCBV by 7% to 39% (control, 4.66 +/- 0.03 to 10.04 +/- 0.12 mL/100 g; sevoflurane, 5.04 +/- 0.03 to 13.6 +/- 0.15 mL/100 g); however, sevoflurane decreased rMTT by 7% to 18% (control, 3.75 +/- 0.04 to 5. 39 +/- 0.04 s; sevoflurane, 3.4 +/- 0.03 to 4.44 +/- 0.03 s) and rCVR by 22% to 36% (control, 0.74 +/- 0.01 to 1.9 +/- 0.2 mm Hg/[mL. 100 g(-1). min(-1)]; sevoflurane, 0.54 +/- 0.01 to 1.41 +/- 0.01 mm Hg/[mL. 100 g(-1). min(-1)]). Interhemispheric differences in rCBF, rCBV, and rCVR were markedly reduced after the administration of sevoflurane. These findings are consistent with the known direct vasodilating effect of sevoflurane. The decrease in rMTT further shows that rCBF increases more than does rCBV. Furthermore, we can show that the observed increase in rCBF during inhalation of sevoflurane is not explained by vasodilation alone.     

Effects of Subanesthetic Doses of Ketamine on Regional Cerebral Blood Flow, Oxygen Consumption, and Blood Volume in Humans

Background: Animal experiments have demonstrated neuroprotection by ketamine. However, because of its propensity to increase cerebral blood flow, metabolism, and intracranial pressure, its use in neurosurgery or trauma patients has been questioned.

Methods: 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine quantitative regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV), respectively, on selected regions of interest of nine healthy male volunteers at baseline and during three escalating concentrations of ketamine (targeted to 30, 100, and 300 ng/ml). In addition, voxel-based analysis for relative changes in rCBF and rCMRO2 was performed using statistical parametric mapping.

Results: The mean +/- SD measured ketamine serum concentrations were 37 +/- 8, 132 +/- 19, and 411 +/- 71 ng/ml. Mean arterial pressure was slightly elevated (maximally by 15.3%, P < 0.001) during ketamine infusion. Ketamine increased rCBF in a concentration-dependent manner. In the region-of-interest analysis, the greatest absolute changes were detected at the highest ketamine concentration level in the anterior cingulate (38.2% increase from baseline, P < 0.001), thalamus (28.5%, P < 0.001), putamen (26.8%, P < 0.001), and frontal cortex (25.4%, P < 0.001). Voxel-based analysis revealed marked relative rCBF increases in the anterior cingulate, frontal cortex, and insula. Although absolute rCMRO2 was not changed in the region-of-interest analysis, subtle relative increases in the frontal, parietal, and occipital cortices and decreases predominantly in the cerebellum were detected in the voxel-based analysis. rCBV increased only in the frontal cortex (4%, P = 0.022).     

Analysis of regional blood flow, blood volume, oxygen and glucose metabolism in heterogeneous parts of untreated high grade gliomas using positron emission tomography (PET)

A high resolution positron emission tomography (PET), HEADTOME III, has enabled us to visualize heterogeneous parts, i.e. viable, necrotic, and edematous portions in malignant gliomas, and to quantify regional hemocirculation and metabolism of the tumors using 15O and 18F-fluorodeoxyglucose tracers. Hemocirculatory and metabolic indices of regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen consumption (rCMRO2) and glucose consumption (rCMRGl) were studied in eight patients with untreated malignant gliomas. Regions of interest (ROIs) in PET images were focused on lesions corresponding to contrast enhancing areas, central low density areas of the tumors, and peritumoral low density areas in CT scans. In the viable portion of the gliomas, rCBV (5.20 +/- 1.18ml/100ml, mean +/- SD, n = 8) was significantly higher than that of the contralateral gray matter (p less than 0.05), which is suggestive of high vascularity; rOEF (0.36 +/- 0.16) and rCMRO2 (1.66 +/- 0.45ml/100ml/min) values markedly decreased (p less than 0.05, p less than 0.01). On the other hand, rCBF (36.3 +/- 13.0ml/100ml/min) and rCMRGl (5.94 +/- 1.15mg/100ml/min) were similar to that of the contralateral gray matter. A relative dissociation between oxygen and glucose metabolism indicates anaerobic glycolysis in the energy metabolism of malignant gliomas. In the central low density area, rCBF, rCBV, rOEF, rCMRO2, rCMRGl values decreased significantly from the viable portion and the contralateral gray matter. rOEF was markedly reduced in the central low density area as compared with that of the peritumoral low density area. The rOEF reduction indicates that oxygen metabolism of gliomas is the first to fail, accompanied by autoregulatory impairment of vessels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sevoflurane for interventional neuroradiology procedures is associated with more rapid early recovery than propofol

PURPOSE: Sevoflurane and propofol are both suitable for neuroanesthesia but have not previously been compared as maintenance agents for long duration (one to five hours) procedures. METHODS: Using a multicentre international study protocol, 103 patients were randomized to receive either sevoflurane or propofol for maintenance of anesthesia during interventional neuroradiology procedures. After a standardized induction of anesthesia with propofol, 53 patients received sevoflurane 1 to 3% with 60% nitrous oxide (N(2)O) in oxygen (O(2)), and 50 patients received propofol 4 to 10 mg x kg(-1) x hr(-1) with 60% N(2)O in O(2). Maintenance agents were titrated against systemic arterial blood pressure (baseline mean arterial pressure +/- 20%). Recovery times, changes in sedation, pain, nausea and vomiting and psychomotor function during recovery and use of rescue medication were recorded. RESULTS: The group receiving sevoflurane had a more rapid recovery to spontaneous ventilation, extubation, eye opening and orientation compared to the group receiving propofol (3 vs 4 min, P = 0.01; 5 vs 6 min, P = 0.015; 7 vs 10 min, P < 0.001; 13 vs 17 min, P = 0.028; respectively). Sedation, pain, nausea and vomiting, and psychomotor function scores were similar in the two groups. Use of opioid boluses and vasopressors were similar. CONCLUSION: The use of sevoflurane for maintenance of anesthesia for prolonged neuroradiological procedures is associated with more rapid early recovery than propofol and is associated with similar side effects. Sevoflurane and propofol can both be recommended for these procedures. The clinical benefit of the more rapid recovery with sevoflurane is unknown.     

Heart rate response to intravenous atropine during propofol anesthesia

During propofol/fentanyl anesthesia, a large percentage of patients have jugular bulb oxygen saturation (SjO(2)) <50%. The incidence is less with isoflurane/N(2)O. We evaluated the effect of N(2)O on SjO(2) during remifentanil-based anesthesia with concurrent propofol or sevoflurane in 20 adults undergoing brain tumor surgery. Anesthesia was randomized: Group 1 (n = 10), target-controlled infusion propofol; and Group 2 (n = 10), thiopental 2-3 mg/kg followed by sevoflurane 0.9% end-tidal. Jugular bulb and arterial blood samples for gas analysis were withdrawn during the administration of oxygen 33% with nitrogen 67% and then with N(2)O 67%. All samples were drawn before surgery and 20 min after the addition of the study gas and with an ETCO(2) 26-28 mm Hg and mean arterial pressure >90 mm Hg. Both groups had similar demographic and physiologic data. In the Propofol group, SjO(2) was 50% +/- 10% with nitrogen and 52% +/- 9% with N(2)O (not significant); in the Sevoflurane group, however, N(2)O 67% increased SjO(2) from 56% +/- 13% to 66% +/- 12% (P < 0.01). This indicates that N(2)O does not reduce the incidence of low SjO(2) values during propofol anesthesia. IMPLICATIONS: This study demonstrates that nitrous oxide can increase jugular bulb venous oxygen saturation when added to sevoflurane/remifentanil anesthesia, but not to propofol/remifentanil anesthesia, in patients with brain tumors.     

The effect of sevoflurane and propofol on cerebral neurotransmitter concentrations during cerebral ischemia in rats

Sevoflurane and propofol are neuroprotective possibly by attenuating central or peripheral catecholamines. We evaluated the effect of these anesthetics on circulating catecholamines and brain neurotransmitters during ischemia in rats. Forty male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: fentanyl and N(2)O/O(2) (control), 2.0% sevoflurane, 0.8-1.2 mg x kg(-1) x min(-1) of propofol, and sham-operated rats with fentanyl and N(2)O/O(2). Ischemia (30 min) was produced by unilateral common carotid artery occlusion plus hemorrhagic hypotension to a mean arterial blood pressure of 32 +/- 2 mm Hg. Pericranial temperature, arterial blood gases, and pH value were maintained constant. Cerebral catecholamine and glutamate concentrations, sampled by microdialysis, and plasma catecholamine concentrations were analyzed using high-pressure liquid chromatography. During ischemia, circulating catecholamines were almost completely suppressed by propofol but only modestly decreased with sevoflurane. Sevoflurane and propofol suppressed brain norepinephrine concentration increases by 75% and 58%, respectively, compared with controls. Intra-ischemia cerebral glutamate concentration was decreased by 60% with both sevoflurane and propofol. These results question a role of circulating catecholamines as a common mechanism for cerebral protection during sevoflurane and propofol. A role of brain tissue catecholamines in mediating ischemic injury is consistent with our results. IMPLICATIONS: During incomplete cerebral ischemia, the neuroprotective anesthetics sevoflurane and propofol suppressed cerebral increases in norepinephrine and glutamate concentrations. In contrast, propofol, but not sevoflurane, suppressed the ischemia-induced increase in circulating catecholamines to baseline levels. The results question a role for plasma catecholamines in cerebral ischemic injury.     

Subanesthetic concentration of sevoflurane increases regional cerebral blood flow more, but regional cerebral blood volume less, than subanesthetic concentration of isoflurane in human volunteers.

Both sevoflurane and isoflurane are used in moderate concentrations in neuroanesthesia practice. The limiting factors for using higher concentrations of inhalational anesthetics in patients undergoing neurosurgery are the agents' effects on cerebral blood flow (CBF) and cerebral blood volume (CBV). In particular, an increase in CBV, which is a key determinant of intracranial pressure, may add to the neurosurgical patient's perioperative risk. To compare the effects of a subanesthetic concentration (0.4 minimum alveolar concentration) of sevoflurane or isoflurane on regional CBF (rCBF), regional CBV (rCBV) and regional mean transit time (rMTT), contrast-enhanced magnetic resonance imaging perfusion measurements were made in spontaneously breathing human volunteers. Absolute changes in rCBF, regional CBV, and rMTT during administration of either drug in regions of interest outlined bilaterally in white and grey matter were nonparametrically (Mann-Whitney test) analyzed. Sevoflurane increased rCBF in practically all regions (absolute change, 4.44 +/- 2.87 to 61.54 +/- 2.39 mL/100g per minute) more than isoflurane did (absolute change, 12.91 +/- 2.52 to 52.67 +/- 3.32 mL/100g per minute), which decreased frontal, parietal, and white matter rCBF (absolute change, -1.12 +/- 0.59 to -14.69 +/- 3.03 mL/100g per minute). Regional CBV was higher in most regions during isoflurane administration (absolute change, 0.75 +/- 0.03 to 4.92 +/- 0.16 mL/100g) than during sevoflurane administration (absolute change, 0.05 +/- 0.14 to 3.57 +/- 0.14 mL/100g). Regional mean transit time was decreased by sevoflurane (absolute change, -0.18 +/- 0.05 to -0.60 +/- 0.04 s) but increased by isoflurane (absolute change, 0.19 +/- 0.03 to 0.69 +/- 0.04 s). In summary, regional CBV was significantly lower during sevoflurane than during isoflurane administration, although sevoflurane increased rCBF more than isoflurane, which even decreased rCBF in some regions. For sevoflurane and, even more pronouncedly, for isoflurane, the observed changes in cerebral hemodynamics cannot be explained by vasodilatation alone.     

The effects of propofol, small-dose isoflurane, and nitrous oxide on cortical somatosensory evoked potential and bispectral index monitoring in adolescents undergoing spinal fusion

In this study we compared the effects of propofol, small-dose isoflurane, and nitrous oxide (N(2)O) on cortical somatosensory evoked potentials (SSEP) and bispectral index (BIS) monitoring in adolescents undergoing spinal fusion. Twelve patients received the following anesthetic maintenance combinations in a randomly determined order: treatment #1: isoflurane 0.4% + N(2)O 70% + O(2) 30%; treatment #2: isoflurane 0.6% + N(2)O 70% + O(2) 30%; treatment #3: isoflurane 0.6% + air + O(2) 30%; treatment #4: propofol 120 microg . kg(-1) . min(-1) + air + O(2) 30%. Cortical SSEP amplitudes measured during anesthesia maintenance with treatment #3 (isoflurane 0.6%/air) were more than those measured during maintenance with treatment #1 (isoflurane 0.4%/N(2)O 70%) (P < 0.0001) and treatment #2 (isoflurane 0.6%/N(2)O 70%) (P < 0.0052). Cortical SSEP amplitudes measured during treatment #4 (propofol 120 microg . kg(-1) . min(-1)/air) were more than treatment #1 (isoflurane 0.4%/N(2)O 70%) (P < 0.0001), treatment #2 (Iso 0.6%/N(2)O 70%) (P < 0.0007), and treatment #3 (isoflurane 0.6%/air) (P < 0.0191). In addition, average BIS values measured during treatments 1, 2, 3 and 4 were 62, 62, 61, and 44 respectively. Only treatment #4 (propofol 120 microg . kg(-1) . min(-1)/air) uniformly maintained BIS values less than 60. Our study demonstrates that propofol better preserves cortical SSEP amplitude measurement and provides a deeper level of hypnosis as measured by BIS values than combinations of small-dose isoflurane/N(2)O or small-dose isoflurane alone.     

The anticonvulsant effects of volatile anesthetics on lidocaine-induced seizures in cats

Large concentrations of sevoflurane and isoflurane, but not halothane, induce spikes in the electroencephalogram. To elucidate whether these proconvulsant effects affect lidocaine-induced seizures, we compared the effects of sevoflurane, isoflurane, and halothane in cats. Fifty animals were allocated to 1 of 10 groups: 70% nitrous oxide (N2O), 0.6 minimum alveolar anesthetic concentration (MAC) + 70% N2O, 1.5 MAC + 70% N2O, and 1.5 MAC of each volatile agent in oxygen. Lidocaine 4 mg x kg(-1) x min(-1) was infused IV under mechanical ventilation with muscle relaxation. Electroencephalogram in the cortex, amygdala, and hippocampus and multiunit activities in the midbrain reticular formation (R-MUA) were recorded. Lidocaine induced spikes first from the amygdala or hippocampus in the 70% N2O and halothane groups and from the cortex in the sevoflurane and isoflurane groups. Lidocaine induced seizures in all cats in the 70% N2O and 0.6 MAC + N2O groups. Seizure occurrence was reduced in the 1.5 MAC + N2O group (P < 0.05 versus 70% N2O). The onset of seizure was delayed in the 0.6 MAC + N2O and 1.5 MAC groups for sevoflurane and isoflurane, but not for halothane, compared with the 70% N2O group (P < 0.05). Lidocaine increased R-MUA with seizure by 130%+/-56% in the 70% N2O group. The increase of R-MUA with seizure was more suppressed in the volatile anesthetic groups than in the 70% N2O group (P < 0.05). In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased. IMPLICATIONS: Increasingly, epidural blockade is combined with general anesthesia to achieve stress-free anesthesia and continuous pain relief in the postoperative period. In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased.     

Sevoflurane provides better recovery than propofol plus fentanyl in anaesthesia for day-care surgery

To compare ease of maintenance and recovery characteristics of sevoflurane and propofol plus fentanyl in day-care anaesthesia, 60 outpatients undergoing elective surgery of up to 3 h duration were randomized to receive sevoflurane or propofol as their primary anaesthetic. Induction was always carried out with propofol, but a fentanyl bolus 5 microg kg-1 was added in the propofol group. Anaesthesia was supplemented with up to 70% N2O. Significantly shorter times to extubation (10.03 min +/- 3.2 SD vs. 17.2 +/- 7.3; P < 0.001) and emergence (10.4 +/- 3.1 vs. 16.8 +/- 6.4; P < 0.001) were observed in the sevoflurane group. Patients treated with sevoflurane felt less confused, showed better performances in the digit symbol substitution test and achieved higher modified Aldrete scores sooner in the post-operative course. Maintenance of anaesthesia with sevoflurane produces faster emergence and recovery than propofol plus fentanyl after anaesthesia of short to intermediate duration.     

Cerebral blood volume is increased in dogs during administration of nitrous oxide or isoflurane

Positron emission tomography was used to study the effects of nitrous oxide (N2O) and isoflurane on regional cerebral blood volume (rCBV) in dogs during normocapnia and hypocapnia. Regional cerebral blood volume was measured serially during the addition of 50% N2O to a background anesthetic of fentanyl in normocapnic (group 1) and hypocapnic (PaCO2 25 mmHg, group 2) dogs. In each group, after 15 min of N2O administration accompanied by rCBV measurement, elimination of N2O with 100% O2 was continued for 15 min. This was followed by introduction of 2% isoflurane (no N2O), again accompanied by serial measurements of rCBV. In the normocapnic animals, the addition of 50% N2O caused an 11% increase in rCBV (6.1 +/- 1.4 to 6.8 +/- 1.0 ml/100 g, P less than 0.02) while 2% isoflurane caused a 36% increase (6.1 +/- 1.3 to 8.0 +/- 1.7 ml/100 g, P less than 0.02). The initial induction of hypocapnia during infusion of fentanyl in group 2 animals was associated with a 17% decrease in rCBV. In the hypocapnic dogs, there was no change in rCBV when N2O was introduced; however, an increase of 15% occurred following the addition of isoflurane (3.9 +/- 0.6 to 4.5 +/- 0.7 ml/100 g, P less than 0.02). Isoflurane, even during hypocapnia, may increase cerebral blood volume which in some circumstances may lead to an increase in ICP.     

Sevoflurane and isoflurane, but not propofol, decrease mivacurium requirements over time

PURPOSE: Volatile anesthetic agents potentiate neuromuscular blockade, but the magnitude of potentiation appears to be time dependent. The time course of this interaction was studied by measuring mivacurium infusion rates during sevoflurane, isoflurane and propofol anesthesia. METHODS: After informed consent, anesthesia was induced in 48 ASA physical status I-II adults with propofol, fentanyl and mivacurium 0.25 mg.kg(-1) and maintained with N(2)O (60%) and one of the three agents chosen at random: sevoflurane 1.9%; isoflurane 1.2%; or propofol 100-150 microgram.kg(-1).min(-1). Train-of-four stimulation was applied every 15 sec to the ulnar nerve. Neuromuscular blockade was monitored with accelerometry. At 5% recovery of the first twitch (T1), a mivacurium infusion was started and adjusted every five minutes to maintain 90-95% T1 depression. RESULTS: The time to 5% T1 recovery after the initial dose was similar in all groups (13-15 min). Fifteen minutes after the start of the infusion mivacurium requirements were greater (P < 0.05) in the propofol group (7.5 +/- 1.7 microgram.kg(-1).min(-1); mean +/- SD) than in either isoflurane (4.7 +/- 1.6 microgram.kg(-1).min(-1)) or sevoflurane (4.5 +/- 1.5 microgram.kg(-1).min(-1)) group. Then, the rate remained stable for propofol (6.2 +/- 1.4 microgram.kg(-1).min(-1) after 90 min of infusion) while it decreased with isoflurane to 2.9 +/- 1.6 microgram.kg(-1).min(-1) at 90 min (P < 0.05 vs propofol) and to 1.4 +/- 1.0 microgram.kg(-1).min(-1) in the sevoflurane group (P < 0.05 vs propofol and isoflurane). CONCLUSION: Sevoflurane and isoflurane do not prolong the effect of a bolus dose of mivacurium, but potentiation increases with time from 30-105 min of exposure. This interaction is greater with sevoflurane than isoflurane.     

Maintenance and recovery characteristics after sevoflurane or propofol during ambulatory surgery in children with epidural blockade

PURPOSE: To compare the maintenance and recovery characteristics after sevoflurane with those after propofol in children with epidural blockade. METHODS: Fifty unpremedicated, children ASA I-II, 2-8 yr of age, scheduled for elective urological surgery as outpatients, were randomly allocated to receive either: 1) sevoflurane for induction and maintenance of anaesthesia or 2) propofol for induction (2-3 mg.kg-1 i.v.) and for maintenance (5-10 mg.kg-1.hr-1 i.v.). All children received N2O 70% in oxygen before induction and throughout the anaesthetic, rocuronium for neuromuscular blockade and a lumbar or caudal epidural block before incision. Heart rate (HR), systolic blood pressure (SBP), recovery times and all side effects during maintenance and recovery were recorded by a blinded observer. Adverse events during the first 24 hr were also recorded. RESULTS: Mean HR increased 5-10% after induction in both groups reaching a maximum by five minutes. Heart rate returned to baseline by skin incision in the sevoflurane group and by 10 min after induction in the propofol group. During maintenance, HR decreased by 10-20% below baseline values by 20 min in the propofol group only, where it remained for the remainder of the anaesthetic. Similarly, SBP increased by 10% after induction of anaesthesia in both groups, but returned to baseline by 10 min. Light anaesthesia occurred in four (16%) children, all in the propofol group. Emergence and recovery indices were similar in the two groups. DISCUSSION: Sevoflurane and propofol exhibit similar maintenance and recovery profiles when combined with epidural analgesia in children undergoing ambulatory surgery.     

Acute Pain and Central Nervous System Arousal Do Not Restore Impaired Hypoxic Ventilatory Response during Sevoflurane Sedation

Background: To quantify the effects of acute pain on ventilatory control in the awake and sedated human volunteer, the acute hypoxic ventilatory response was studied in the absence and presence of noxious stimulation before and during 0.1 minimum alveolar concentration sevoflurane inhalation.

Methods: Step decreases in end-tidal partial pressure of oxygen from normoxia into hypoxia (approximately 50 mmHg) were performed in 11 healthy volunteers. Four acute hypoxic ventilatory responses were obtained per subject: one in the absence of pain and sevoflurane (C), one in the absence of sevoflurane with noxious stimulation in the form of a 1-Hz electrical current applied to the skin over the tibial bone (C + P), one in the absence of pain during the inhalation of 0.1 minimum alveolar concentration sevoflurane (S), and one during 0.1 minimum alveolar concentration sevoflurane with noxious stimulation (S + P). The end-tidal partial pressure of carbon dioxide was held constant at a value slightly greater than baseline (44 mmHg). To assess the central nervous system arousal state, the bispectral index of the electroencephalogram was monitored. Values are mean+/-SE.

Results: Pain caused an increase in prehypoxic baseline ventilation before and during sevoflurane inhalation: C = 13.7+/-0.9 l *symbol* min-1, C + P = 16.0+/-1.0 l *symbol* min-1 (P < 0.05 vs. C and S), S = 12.7+/-1.2 l *symbol* min-1, and S + P = 15.9+/-1.1 l *symbol* min-1 (P < 0.05 vs. C and S). Sevoflurane decreased the acute hypoxic ventilatory response in the absence and presence of noxious stimulation: C = 0.69+/-0.20 l *symbol* min-1 (% change in arterial hemoglobin-oxygen saturation derived from pulse oximetry [SP O2])-1, C + P = 0.64 +/-0.13 l *symbol* min-1 *symbol* %SP O2-1, S = 0.48+/-0.15 l *symbol* min-1 *symbol* %SP O2-1 (P < 0.05 vs. C and C + P) and S + P = 0.46+/-0.12 l *symbol* min-1 *symbol* %SP O2-1 (P < 0.05 vs. C and C + P). The bispectral indexes were C = 96.2+/-0.7, C + P = 97.1 +/-0.4, S = 86.3+/-1.3 (P < 0.05), and S + P = 95.0 +/-1.0.     

Propofol alone,sevoflurane alone,and combined propofol-sevoflurane anaesthesia in electroconvulsive therapy

Electroconvulsive therapy is an effective treatment for severe and medication-resistant depression. There have been no reports describing how a volatile anaesthetic affects haemodynamic responses, seizure duration, and recovery characteristics during electroconvulsive therapy. We carried out a repeated-measure crossover study to compare the effects on haemodynamic responses, seizure duration, and recovery characteristics of the following types of anaesthesia in electroconvulsive therapy: propofol alone, sevoflurane alone, and propofol combined with sevoflurane. We recruited 50 patients requiring electroconvulsive therapy for depression. For anaesthesia induction, 1.5 mg/kg propofol (condition P), 5% sevoflurane in oxygen following a vital capacity rapid inhalation induction (condition S), or 1.5 mg/kg propofol followed by 5% sevoflurane in oxygen (condition PS) was administered. Succinylcholine 1.5 mg/kg was then given. Electrical stimulation was administered after fasciculation. Measurements were obtained before anaesthesia induction (baseline), prior to succinylcholine administration, prior to electroconvulsive therapy, and at the peak after electroconvulsive therapy. After electroconvulsive therapy, peak heart rate and peak mean arterial pressure were highest in condition S. Whereas recovery time was longest in condition PS, motor seizure duration was significantly shorter than in either condition P or S. Electroencephalographic seizure duration was significantly shorter in condition PS than in condition P and significantly shorter in condition S than in condition P. Sevoflurane anaesthesia alone is most disadvantageous in terms of haemodynamics. Propofol-sevoflurane anaesthesia is advantageous in terms of haemodynamics, but disadvantageous in terms of seizure duration and recovery time. Propofol alone is most advantageous in terms of seizure duration.     

Jugular bulb oxygen saturation under propofol or sevoflurane/nitrous oxide anesthesia during deliberate mild hypothermia in neurosurgical patients

Sevoflurane and propofol have been widely used as anesthetic agents for neurosurgery. Recent evidence has suggested that the influence of these anesthetics on cerebral oxygenation may differ. In the present study, the authors investigated jugular bulb oxygen saturation (SjO2) during propofol and sevoflurane/nitrous oxide anesthesia under mildly hypothermic conditions. After institutional approval and informed consent, 20 patients undergoing elective craniotomy were studied. Patients were randomly divided to the group S/N2O (sevoflurane/nitrous oxide/fentanyl anesthesia) or the group P (propofol/fentanyl anesthesia). After induction of anesthesia, the catheter was inserted retrograde into the jugular bulb and SjO2 was analyzed. During the operation, patients were cooled and tympanic membrane temperature was maintained at 34.5 degrees C. SjO2 was measured at normocapnia during mild hypothermia and at hypocapnia during mild hypothermia. There were no statistically significant differences in demographic variables between the groups. During mild hypothermia, SjO2 values were significantly lower in group P than in group S/N2O. The incidence of SjO2 less than 50% under mild hypothermic-hypocapnic conditions was significantly higher in group P than in group S/N2O. These results suggest that hyperventilation should be more cautiously applied during mild hypothermia in patients anesthetized with propofol and fentanyl versus sevoflurane/nitrous oxide/fentanyl.     

Electrophysiologic Mechanism Underlying Action Potential Prolongation by Sevoflurane in Rat Ventricular Myocytes

Background: Despite prolongation of the QTc interval in humans during sevoflurane anesthesia, little is known about the mechanisms that underlie these actions. In rat ventricular myocytes, the effect of sevoflurane on action potential duration and underlying electrophysiologic mechanisms were investigated.

Methods: The action potential was measured by using a current clamp technique. The transient outward K+ current was recorded during depolarizing steps from -80 mV, followed by brief depolarization to -40 mV and then depolarization up to +60 mV. The voltage dependence of steady state inactivation was determined by using a standard double-pulse protocol. The sustained outward current was obtained by addition of 5 mm 4-aminopyridine. The inward rectifier K+ current was recorded from a holding potential of -40 mV before their membrane potential was changed from -130 to 0 mV. Sevoflurane actions on L-type Ca2+ current were also obtained.

Results: Sevoflurane prolonged action potential duration, whereas the amplitude and resting membrane potential remained unchanged. The peak transient outward K+ current at +60 mV was reduced by 18 +/- 2% (P < 0.05) and 24 +/- 2% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively. Sevoflurane had no effect on the sustained outward current. Whereas 0.7 mm sevoflurane did not shift the steady state inactivation curve, it accelerated the current inactivation (P < 0.05). The inward rectifier K+ current at -130 mV was little altered by 0.7 mm sevoflurane. L-type Ca2+ current was reduced by 28 +/- 3% (P < 0.05) and 33 +/- 1% (P < 0.05) by 0.35 and 0.7 mm sevoflurane, respectively.     

Isoflurane and Sevoflurane Anesthesia in Pigs with a Preexistent Gas Exchange Defect

Background : Decreased arterial partial pressure of oxygen (Pao2) during volatile anesthesia is well-known. Halothane has been examined with the multiple inert gas elimination technique and has been shown to alter the distribution of pulmonary blood flow and thus Pao2. The effects of isoflurane and sevoflurane on pulmonary gas exchange remain unknown. The authors hypothesized that sevoflurane with a relatively high minimum alveolar concentration (MAC) would result in significantly more gas exchange disturbances in comparison with isoflurane or control.

Methods : This study was performed in a porcine model with an air pneumoperitoneum that generates a reproducible gas exchange defect. After a baseline measurement of pulmonary gas exchange (multiple inert gas elimination technique) during propofol anesthesia, 21 pigs were randomly assigned to three groups of seven animals each. One group received isoflurane anesthesia, one group received sevoflurane anesthesia, and one group was continued on propofol anesthesia (control). After 30 min of volatile anesthesia at 1 MAC or propofol anesthesia, a second measurement (multiple inert gas elimination technique) was performed.

Results : At the second measurement, inert gas shunt was 15 +/- 3% (mean +/- SD) during sevoflurane anesthesia versus 9 +/- 1% during propofol anesthesia (P = 0.02). Blood flow to normal ventilation/perfusion ( A/ ) lung areas was 83 +/- 5% during sevoflurane anesthesia versus 89 +/- 1% during propofol anesthesia (P = 0.04). This resulted in a Pao2 of 88 +/- 11 mmHg during sevoflurane anesthesia versus 102 +/- 15 mmHg during propofol anesthesia (P = 0.04). Inert gas and blood gas variables during isoflurane anesthesia did not differ significantly from those obtained during propofol anesthesia.