Effects of dose-dependent levels of isoflurane on cerebral blood flow in healthy subjects studied using positron emission tomography

Background:  In this study, we tested the hypothesis that escalating drug concentrations of isoflurane are associated with a significant decline in cerebral blood flow (CBF) in regions sub-serving conscious brain activity, including specifically the thalamus.
Methods:  Nine human volunteers received three escalating drug concentrations: 0.2, 0.4 and 1.0 MAC end-tidal inhalation. During waking, baseline and the three levels of sedation, a     O PET scan was performed.
Results:  Isoflurane decreased the bispectral index (BIS) values dose-dependently. Cardiovascular and respiratory parameters were maintained constant over time. No significant change in global CBF was observed. Throughout all three MAC levels of sedation, isoflurane caused an increased regional cerebral blood flow (rCBF) in the anterior cingulate and decreased rCBF in the cerebellum. Initially, isoflurane (0 vs. 0.2 MAC) significantly increased relative rCBF in the medial frontal gyrus and in the nucleus accumbens. At the next level (0.2 vs. 0.4 MAC), relative rCBF was significantly increased in the caudate nucleus and decreased in the lingual gyrus and cuneus. At the last level (0.4 vs. 1 MAC), relative rCBF was significantly increased in the insula and decreased in the thalamus, the cuneus and lingual gyrus. Compared with flow distribution in awake volunteers, 1 MAC of isoflurane significantly raised relative activity in the anterior cingulate and insula regions. In contrast, a significant relative flow reduction was identified in the thalamus, the cerebellum and lingual gyrus.
Conclusions:  Isoflurane, like sevoflurane, induced characteristic flow redistribution at doses of 0.2–1.0 MAC. At 1 MAC of isoflurane, rCBF decreased in the thalamus. Specific areas affected by both isoflurane and sevoflurane included the anterior cingulate, insula regions, cerebellum, lingual gyrus and thalamus.     

Effects of subanaesthetic and anaesthetic doses of sevoflurane on regional cerebral blood flow in healthy volunteers. A positron emission tomographic study

BACKGROUND: We tested the hypothesis that escalating drug concentrations of sevoflurane are associated with a significant decline of cerebral blood flow in regions subserving conscious brain activity, including specifically the thalamus. METHODS: Nine healthy human volunteers received three escalating doses using 0.4%, 0.7% and 2.0% end-tidal sevoflurane inhalation. During baseline and each of the three levels of anaesthesia one PET scan was performed after injection of . Cardiovascular and respiratory parameters were monitored and electroencephalography and bispectral index (BIS) were registered. RESULTS: Sevoflurane decreased the BIS values dose-dependently. No significant change in global cerebral blood flow (CBF) was observed. Increased regional CBF (rCBF) in the anterior cingulate (17-21%) and decreased rCBF in the cerebellum (18-35%) were identified at all three levels of sedation compared to baseline. Comparison between adjacent levels sevoflurane initially (0 vs. 0.2 MAC) decreased rCBF significantly in the inferior temporal cortex and the lingual gyrus. At the next level (0.2 MAC vs. 0.4 MAC) rCBF was increased in the middle temporal cortex and in the lingual gyrus, and decreased in the thalamus. At the last level (0.4 MAC vs. 1 MAC) the rCBF was increased in the insula and decreased in the posterior cingulate, the lingual gyrus, precuneus and in the frontal cortex. CONCLUSION: At sevoflurane concentrations at 0.7% and 2.0% a significant decrease in relative rCBF was detected in the thalamus. Interestingly, some of the most profound changes in rCBF were observed in structures related to pain processing (anterior cingulate and insula).     

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 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 microg/ml during propofol alone and 3.5 +/- 0.7 microg/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. CONCLUSIONS: Propofol reduced rCBF and rCMRO2 comparably. Sevoflurane reduced rCBF less than propofol but rCMRO2 to an extent similar to propofol. These reductions in flow and metabolism were partly attenuated by adjunct N2O. S+N especially reduced the oxygen extraction fraction, suggesting disturbed flow-activity coupling in humans at a moderate depth of anesthesia.     

Neural mechanism of propofol anesthesia in severe depression: a positron emission tomographic study

BACKGROUND: The precise neural mechanisms of propofol anesthesia in humans are still unknown. The authors examined the acute effects of propofol on regional cerebral blood flow (rCBF) using positron emission tomography in patients with severe depression. METHODS: In six severely depressed patients (mean age, 55.0 yr) scheduled for electroconvulsive therapy, anesthetic levels were monitored by electroencephalography, and rCBF was serially quantified in the awake, sedated, and anesthetized states. The authors used high-resolution positron emission tomography with 15O-labeled water and statistical parametric mapping 99 for imaging and analysis of the data. RESULTS: Global cerebral blood flow showed sharp decreases from the awake level during the administration of propofol, decreasing 26.8% in the sedated state and 54.4% in the anesthetized state. Moreover, a dose effect was seen in both parietal cortices and the left lateral prefrontal region with larger regions of relative decrease in rCBF at higher propofol doses. At the higher dose, the values of rCBF in the pulvinar nucleus of the thalamus, the pontine tegmentum, and the cerebellar cortex were also affected. Meanwhile, there were few changes of relative rCBF in the basal frontal lobes during both sedated and anesthetized states. CONCLUSIONS: As in earlier studies using normal subjects, pronounced suppression in rCBF in the brain stem reticular formation, the thalamus, and the parietal association cortex occurred even in severely depressed patients. However, previously reported decreases in rCBF in the basal frontal lobe were absent in depressed patients.     

Neural Mechanism of Propofol Anesthesia in Severe Depression: A Positron Emission Tomographic Study

Background: The precise neural mechanisms of propofol anesthesia in humans are still unknown. The authors examined the acute effects of propofol on regional cerebral blood flow (rCBF) using positron emission tomography in patients with severe depression.

Methods: In six severely depressed patients (mean age, 55.0 yr) scheduled for electroconvulsive therapy, anesthetic levels were monitored by electroencephalography, and rCBF was serially quantified in the awake, sedated, and anesthetized states. The authors used high-resolution positron emission tomography with 15O-labeled water and statistical parametric mapping 99 for imaging and analysis of the data.

Results: Global cerebral blood flow showed sharp decreases from the awake level during the administration of propofol, decreasing 26.8% in the sedated state and 54.4% in the anesthetized state. Moreover, a dose effect was seen in both parietal cortices and the left lateral prefrontal region with larger regions of relative decrease in rCBF at higher propofol doses. At the higher dose, the values of rCBF in the pulvinar nucleus of the thalamus, the pontine tegmentum, and the cerebellar cortex were also affected. Meanwhile, there were few changes of relative rCBF in the basal frontal lobes during both sedated and anesthetized states.     

The effects of sevoflurane and hyperventilation on electrocorticogram spike activity in patients with refractory epilepsy

We investigated the effects of sevoflurane and hyperventilation on intraoperative electrocorticogram (ECoG) spike activity in 13 patients with intractable epilepsy. Grid electrodes were placed on the brain surface and ECoG was recorded under the following conditions: 1) 0.5 minimal alveolar anesthetic concentration (MAC) sevoflurane, 2) 1.5 MAC sevoflurane, and 3) 1.5 MAC sevoflurane with hyperventilation. The number of spikes per 5 min and the percentage of leads with spikes were assessed in each condition. In 4 patients with chronically implanted-subdural electrodes, the leads with seizure onset and with spikes during the interictal periods in the awake state were compared with those during sevoflurane anesthesia at 0.5 MAC and 1.5 MAC. The number of spikes and the percentage of leads with spikes were significantly more under 1.5 MAC sevoflurane anesthesia compared with those under 0.5 MAC sevoflurane (P < 0.05). The induction of hyperventilation significantly increased the number of spikes and percentage of leads with spikes (P < 0.05). With 0.5 MAC sevoflurane, the leads with spikes were similar to those at seizure onset in the awake state, whereas with 1.5 MAC sevoflurane, spikes were similar to those occurring during interictal periods in the awake state. These results indicate that sevoflurane and hyperventilation can affect the frequency and extent of ECoG spike activity in patients with intractable epilepsy. Careful attention should be paid to the concentration of sevoflurane used and ventilatory status when intraoperative EcoG is used to localize epileptic lesions. IMPLICATIONS: Electrocorticogram can be used to define the location and extent of epileptic foci during epilepsy surgery. However, electrocorticogram can be affected by anesthetic technique. The present study found that sevoflurane concentration and hyperventilation affected the frequency and the extent of electrocorticogram spike activity in epileptic patients.     

Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry.

BACKGROUND: Anesthetic agents alter pharyngeal function with risk of impaired airway protection and aspiration. This study was performed to evaluate pharyngeal function during subhypnotic concentrations of propofol, isoflurane, and sevoflurane and to compare the drugs for possible differences in this respect. METHODS: Forty-five healthy volunteers were randomized to receive propofol, isoflurane, or sevoflurane. During series of liquid contrast bolus swallowing, fluoroscopy and simultaneous solid state videomanometry was used to study the incidence of pharyngeal dysfunction, the initiation of swallowing, and the bolus transit time. Pressure changes were recorded at the back of the tongue, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, the anesthetic was delivered, and measurements were made at 0.50 and 0.25 predicted blood propotol concentration (Cp50(asleep)) for propofol and 0.50 and 0.25 minimum alveolar concentration (MAC)(awake) for the inhalational agents. Final recordings were made 20 min after the end of anesthetic delivery. RESULTS: All anesthetics caused an increased incidence of pharyngeal dysfunction with laryngeal bolus penetration. Propofol increased the incidence from 8 to 58%, isoflurane from 4 to 36%, and sevoflurane from 6 to 35%. Propofol in 0.50 and 0.25 Cp50(asleep) had the most extensive effect on the pharyngeal contraction patterns (P < 0.05). The upper esophageal sphincter resting tone was markedly reduced from 83 +/- 36 to 39 +/- 19 mmHg by propofol (P < 0.001), which differed from isoflurane (P = 0.03). Sevoflurane also reduced the upper esophageal sphincter resting tone from 65 +/- 16 to 45 +/- 18 mmHg at 0.50 MAC(awake)(P = 0.008). All agents caused a reduced upper esophageal sphincter peak contraction amplitude (P < 0.05), and the reduction was greatest in the propofol group (P = 0.002). CONCLUSION: Subhypnotic concentrations of propofol, isoflurane, and sevoflurane cause an increased incidence of pharyngeal dysfunction with penetration of bolus to the larynx. The effect on the pharyngeal contraction pattern was most pronounced in the propofol group, with markedly reduced contraction forces.     

The minimum alveolar concentration (MAC) and hemodynamic effects of halothane, isoflurane, and sevoflurane in newborn swine

To determine the minimum alveolar concentration (MAC) and hemodynamic responses to halothane, isoflurane, and sevoflurane in newborn swine, 36 fasting swine 4-10 days of age were anesthetized with one of the three volatile anesthetics in 100% oxygen. MAC was determined for each swine. Carotid artery and internal jugular catheters were inserted and each swine was allowed to recover for 48 h. After recovery, heart rate (HR), systemic systolic arterial pressure (SAP), and cardiac index (CI) were measured awake and then at 0.5, 1.0, and 1.5 MAC of the designated anesthetic in random sequence. The (mean +/- SD) MAC for halothane was 0.90 +/- 0.12%; the MAC for isoflurane was 1.48 +/- 0.21%; and the MAC for sevoflurane was 2.12 +/- 0.39%. Awake (mean +/- SD) measurements of HR, SAP, and CI did not differ significantly among the three groups. Compared to the awake HR, the mean HR decreased 35% at 1.5 MAC halothane (P less than 0.001), 19% at 1.5 MAC isoflurane (P less than 0.005), and 31% at 1.5 MAC sevoflurane (P less than 0.005). Compared to awake SAP, mean SAP measurements decreased 46% at 1.5 MAC halothane (P less than 0.001), 43% at 1.5 MAC isoflurane (P less than 0.001), and 36% at 1.5 MAC sevoflurane (P less than 0.005). Mean SAP at 1.0 and 1.5 MAC halothane and isoflurane were significantly less than those measured at equipotent concentrations of sevoflurane (P less than 0.005). Compared to awake CI, mean CI measurements decreased 53% at 1.5 MAC halothane (P less than 0.001) and 43% at 1.5 MAC isoflurane (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intravenous anesthesia with propofol on regional cortical blood flow and intracranial pressure in surgery for moyamoya disease

BACKGROUND: The aim of this study was to compare the effects of inhalation anesthesia with sevoflurane and intravenous anesthesia with propofol on ICP and rCoBF during revascularization surgery for patients with MMD. METHODS: Between 1999 and 2004, a total of 90 revascularization surgeries were performed on 58 patients. Among them, in 20 consecutive operations on 14 patients, continuous monitoring of ICP was performed with an ICP monitoring probe. Subsequently, in 14 consecutive operations on 9 patients (CoBF group), intraoperative monitoring of rCoBF was carried out with a laser Doppler flowmeter probe. The monitoring of ICP and rCoBF was performed for more than 20 minutes after the administration of anesthetic was changed from 1.5% to 2.5% sevoflurane to 6 mg/kg per hour of propofol. In all cases, the Paco(2) of these patients was strictly maintained between 38 and 40 mm Hg throughout the operations. RESULTS: In both the ICP and the CoBF groups, the values of physiologic parameters obtained under inhalation anesthesia did not differ statistically from those obtained under intravenous anesthesia. The value for ICP under anesthesia with propofol was significantly lower than that under anesthesia with sevoflurane (P < .0001). The value for rCoBF in the frontal lobe under anesthesia with propofol was significantly higher than that under anesthesia with sevoflurane. CONCLUSIONS: Intravenous anesthesia with propofol has potential to provide brain protection and preservation of rCBF in the frontal lobes in surgery for MMD. Whether choice of anesthetic agents might be important in surgery for MMD should be investigated further.     

Sevoflurane Increases Lumbar Cerebrospinal Fluid Pressure in Normocapnic Patients Undergoing Transsphenoidal Hypophysectomy

Background: The data on the effect of sevoflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that sevoflurane would increase intracranial pressure as compared to propofol.

Methods: In 20 patients with no evidence of mass effect undergoing transsphenoidal hypophysectomy, anesthesia was induced with intravenous fentanyl and propofol and maintained with 70% nitrous oxide in oxygen and a continuous propofol infusion, 100 [micro sign]g [middle dot] kg-1 [middle dot] min-1. The authors assigned patients to two groups randomized to receive only continued propofol infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of sevoflurane for 10 min each. The authors continuously monitored lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations.

Results: Lumbar CSF pressure increased by 2 +/- 2 mmHg (mean +/- SD) with both 0.5 MAC and 1 MAC of sevoflurane. Cerebral perfusion pressure decreased by 11 +/- 5 mmHg with 0.5 MAC and by 15 +/- 4 mmHg with 1.0 MAC of sevoflurane. Systolic blood pressure decreased with both concentrations of sevoflurane. To maintain blood pressure within predetermined limits (within +/- 20% of baseline value), phenylephrine was administered to 5 of 10 patients in the sevoflurane group (range = 50-300 [micro sign]g) and no patients in the propofol group. Lumbar CSF pressure, cerebral perfusion pressure, and systolic blood pressure did not change in the propofol group.     

Propofol and Sevoflurane in Subanesthetic Concentrations Act Preferentially on the Spinal Cord: Evidence from Multimodal Electrophysiological Assessment

Background: Animal experiments in recent years have shown that attenuation of motor responses by general anesthetics is mediated at least partly by spinal mechanisms. Less is known about the relative potency of anesthetic drugs in suppressing cortical and spinal electrophysiological responses in vivo in humans, particularly those, but not only those, connected with motor responses. Therefore, we studied the effects of sevoflurane and propofol in humans using multimodal electrophysiological assessment.

Methods: We studied nine healthy volunteers in two sessions during steady state sedation with 0.5, 1.0, and 1.5 [mu]g/l (targeted plasma concentration) propofol or 0.2 and 0.4 vol% (end-tidal) sevoflurane. Following a 15-min equilibration period, motor responses to transcranial magnetic stimulation and peripheral (H-reflex, F-wave) stimulation were recorded, while electroencephalography and auditory evoked responses were recorded in parallel.

Results: At concentrations corresponding to two thirds of C50 awake, motor responses to transcranial magnetic stimulation were reduced by approximately 50%, H-reflex amplitude was reduced by 22%, F-wave amplitude was reduced by 40%, and F-wave persistence was reduced by 25%. No significant differences between sevoflurane and propofol were found. At this concentration, the Bispectral Index was reduced by 7%, and the middle-latency auditory evoked responses were attenuated only mildly (Nb latency increased by 11%, amplitude PaNb did not change). In contrast, the postauricular reflex was suppressed by 77%.     

Direct cerebral vasodilatory effects of sevoflurane and isoflurane.

BACKGROUND: The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram. METHODS: Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 micro/g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels. RESULTS: Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4+/-3 and 17+/-3% at 0.5 and 1.5 MAC sevoflurane; 19+/-3 and 72+/-9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P<0.05). All patients required phenylephrine (100-300 microg) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia. CONCLUSIONS: In common with other volatile anesthetic agents, sevoflurane has an intrinsic dose-dependent cerebral vasodilatory effect. However, this effect is less than that of isoflurane.     

The effect of sevoflurane and isoflurane anesthesia on interictal spike activity among patients with refractory epilepsy.

The electrophysiologic effects of sevoflurane are not well characterized in humans. Among patients with refractory epilepsy, this study compared 1) electroencephalographic (EEG) interictal spike activity during wakefulness and sevoflurane anesthesia, and 2) electrocorticographically (ECoG) recorded interictal spike activity during sevoflurane and isoflurane anesthesia. We studied 12 patients undergoing insertion of subdural electrodes. Before commencing anesthesia, awake (baseline) EEG recordings were obtained. After inhaled induction, EEG interictal spike activity was evaluated during stable, normocapnic, and hypocapnic (Paco2 = 28-30 mm Hg), sevoflurane anesthesia administered at 1.5 times the minimum alveolar anesthetic concentration (1.5 MAC). Immediately after surgery, ECoG recordings were obtained from subdural electrodes during 1) 1.5 MAC isoflurane, 2) 0.3 MAC isoflurane, and 3) 1.5 MAC sevoflurane anesthesia. EEG spike frequency increased in all patients during sevoflurane anesthesia compared with awake recordings (P = 0.002). Compared with 0.3 MAC isoflurane anesthesia, ECoG interictal spike frequency was higher in all patients during 1.5 MAC sevoflurane anesthesia (P = 0.004) and in 8 of 10 patients during 1.5 MAC isoflurane anesthesia (P = 0.016). Under sufficiently rigorous conditions, both sevoflurane and isoflurane can provoke interictal spike activity at near burst-suppression doses. This property is more prominent with sevoflurane than isoflurane. IMPLICATIONS: The results of this study suggest that the capacity to modulate neuroexcitability is a dose-dependent feature of volatile anesthetics that is manifested most prominently at near burst-suppression doses (i.e., 1.5 times the minimum alveolar anesthetic concentration) and is minimal or absent at low doses.     

Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PET

Background: Arterial carbon dioxide tension (PaCO₂) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia‐induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Methods: Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H₂¹⁵O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Results: Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO₂ was decreased from 5.5 ± 0.7 to 3.8 ± 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. Conclusions: This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia.     

Propofol and Sevoflurane Depress Spinal Neurons In Vitro via Different Molecular Targets

Background: The capacity of general anesthetics to produce immobility is primarily spinally mediated. Recently, compelling evidence has been provided that the spinal actions of propofol involve [gamma]-aminobutyric acid type A (GABAA) receptors, whereas the contribution of glycine receptors remains uncertain. The relevant molecular targets of the commonly used volatile anesthetic sevoflurane in the spinal cord are largely unknown, but indirect evidence suggests a mechanism of action distinct from propofol.

Methods: The effects of sevoflurane and propofol on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurons in cultured spinal cord tissue slices obtained from embryonic rats (embryonic days 14-15).

Results: Propofol and sevoflurane reduced spontaneous action potential firing of neurons. Concentrations causing half-maximal effects (0.11 [mu]m propofol, 0.11 mm sevoflurane) were lower than the median effective concentration immobility (1-1.5 [mu]m propofol, 0.35 mm sevoflurane). At higher concentrations, complete inhibition of action potential activity was observed with sevoflurane but not with propofol. Effects of sevoflurane were mediated predominantly by glycine receptors (45%) and GABAA receptors (38%), whereas propofol acted almost exclusively via GABAA receptors (96%).     

Effects of anesthesia on norepinephrine kinetics. Comparison of propofol and halothane anesthesia in dogs

Alteration of sympathetic function is a major determinant of the cardiovascular effects of anesthetic agents. Plasma norepinephrine (NE) concentrations are determined not only by the rate of NE release from sympathetic nerves but also by NE clearance rate. Therefore, NE concentration in plasma may be an inadequate index of sympathetic activity. We used an isotope dilution technique to investigate the effects of halothane and propofol anesthesia on NE kinetics. A relationship of NE kinetics to halothane dose was determined in six dogs. Halothane 1.0 MAC reduced plasma NE concentration by 35 +/- 9% versus awake (P less than 0.05). This was due to a reduction of 52 +/- 9% in NE spillover (P less than 0.05) accompanied by a reduction of 27 +/- 5% in NE clearance (P less than 0.005). The clearance changes were dose-dependent: reductions were 34 +/- 4% at 1.5 MAC (P less than 0.05 vs. 1.0 MAC) and 45 +/- 5% at 2.0 MAC (P less than 0.05 vs. 1.5 MAC). Six dogs were studied with a single halothane dose (1.0 MAC) and NE concentration, spillover, and clearance were found to be stable over a period of 5.5 h of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of aortic blood flow velocity on changes of middle cerebral artery blood flow velocity during isoflurane and sevoflurane anaesthesia

BACKGROUND AND OBJECTIVE: We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia. METHODS: Forty patients (age: isoflurane 24-62 years; sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity. RESULTS: Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; [mean +/- SD] P = 0.0001). CONCLUSIONS: The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.     

Sevoflurane increases lumbar cerebrospinal fluid pressure in normocapnic patients undergoing transsphenoidal hypophysectomy.

BACKGROUND: The data on the effect of sevoflurane on intracranial pressure in humans are still limited and inconclusive. The authors hypothesized that sevoflurane would increase intracranial pressure as compared to propofoL METHODS: In 20 patients with no evidence of mass effect undergoing transsphenoidal hypophysectomy, anesthesia was induced with intravenous fentanyl and propofol and maintained with 70% nitrous oxide in oxygen and a continuous propofol infusion, 100 microg x kg(-1) x min(-1). The authors assigned patients to two groups randomized to receive only continued propofol infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) of sevoflurane for 10 min each. The authors continuously monitored lumbar cerebrospinal fluid (CSF) pressure, blood pressure, heart rate, and anesthetic concentrations. RESULTS: Lumbar CSF pressure increased by 2+/-2 mmHg (mean+/-SD) with both 0.5 MAC and 1 MAC of sevoflurane. Cerebral perfusion pressure decreased by 11+/-5 mmHg with 0.5 MAC and by 15+/-4 mmHg with 1.0 MAC of sevoflurane. Systolic blood pressure decreased with both concentrations of sevoflurane. To maintain blood pressure within predetermined limits (within+/-20% of baseline value), phenylephrine was administered to 5 of 10 patients in the sevoflurane group (range = 50-300 microg) and no patients in the propofol group. Lumbar CSF pressure, cerebral perfusion pressure, and systolic blood pressure did not change in the propofol group. CONCLUSIONS: Sevoflurane, at 0.5 and 1.0 MAC, increases lumbar CSF pressure. The changes produced by 1.0 MAC sevoflurane did not differ from those observed in a previous study with 1.0 MAC isoflurane or desflurane.     

Pharyngeal Function and Airway Protection During Subhypnotic Concentrations of Propofol, Isoflurane, and Sevoflurane: Volunteers Examined by Pharyngeal Videoradiography and Simultaneous Manometry

Background : Anesthetic agents alter pharyngeal function with risk of impaired airway protection and aspiration. This study was performed to evaluate pharyngeal function during subhypnotic concentrations of propofol, isoflurane, and sevoflurane and to compare the drugs for possible differences in this respect.

Methods : Forty-five healthy volunteers were randomized to receive propofol, isoflurane, or sevoflurane. During series of liquid contrast bolus swallowing, fluoroscopy and simultaneous solid state videomanometry was used to study the incidence of pharyngeal dysfunction, the initiation of swallowing, and the bolus transit time. Pressure changes were recorded at the back of the tongue, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, the anesthetic was delivered, and measurements were made at 0.50 and 0.25 predicted blood propotol concentration (Cp50asleep) for propofol and 0.50 and 0.25 minimum alveolar concentration (MAC)awake for the inhalational agents. Final recordings were made 20 min after the end of anesthetic delivery.

Results : All anesthetics caused an increased incidence of pharyngeal dysfunction with laryngeal bolus penetration. Propofol increased the incidence from 8 to 58%, isoflurane from 4 to 36%, and sevoflurane from 6 to 35%. Propofol in 0.50 and 0.25 Cp50asleep had the most extensive effect on the pharyngeal contraction patterns (P < 0.05). The upper esophageal sphincter resting tone was markedly reduced from 83 +/- 36 to 39 +/- 19 mmHg by propofol (P < 0.001), which differed from isoflurane (P = 0.03). Sevoflurane also reduced the upper esophageal sphincter resting tone from 65 +/- 16 to 45 +/- 18 mmHg at 0.50 MACawake (P = 0.008). All agents caused a reduced upper esophageal sphincter peak contraction amplitude (P < 0.05), and the reduction was greatest in the propofol group (P = 0.002).