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Background We hypothesized that, compared with propofol, desflurane prolongs the antegrade accessory pathway effective refractory period (APERP) in children undergoing radiofrequency catheter ablation for Wolff-Parkinson-White (WPW) syndrome. Methods In this randomized crossover study, children aged 4.1−16.1 years undergoing radiofrequency catheter ablation for WPW syndrome were randomly divided into four groups according to the concentration of desflurane and anesthetics used in the first and the second electrophysiological studies (EPS). After induction of general anesthesia with propofol and tracheal intubation, they received one of the following regimens: 0.5 minimum alveolar concentration (MAC) desflurane (first EPS) and propofol (second EPS) (Des0.5-Prop group, n = 8); propofol (first EPS) and 0.5 MAC desflurane (second EPS) (Prop-Des0.5 group, n = 9); 1 MAC desflurane (first EPS) and propofol (second EPS) (Des1.0-Prop group, n = 10); propofol (first EPS) and 1 MAC desflurane (second EPS) (Prop-Des1.0 group, n = 9). Radiofrequency catheter ablation was performed upon completion of EPS. Sample size was determined to detect a difference in the APERP. Results Desflurane at 1.0 MAC significantly prolonged the APERP compared with propofol, but did not affect the sinoatrial conduction time, atrio-His interval or atrioventricular node effective refractory period. Supraventricular tachycardia was induced in all children receiving propofol, but not induced in 1 and 4 children receiving 0.5 MAC and 1.0 MAC desflurane, respectively. Conclusion Desflurane enhances the refractoriness and may block the electrical conduction of the atrioventricular accessory pathway, and is therefore not suitable for use in children undergoing radiofrequency catheter ablation for WPW syndrome.

Background Neuroprotection from therapeutic hypothermia increases when combined with the anaesthetic gas xenon in animal studies. A clinical feasibility study of the combined treatment has been successfully undertaken in asphyxiated human term newborns. It is unknown whether xenon alone would be sufficient for sedation during hypothermia eliminating or reducing the need for other sedative or analgesic infusions in ventilated sick infants. Minimum alveolar concentration (MAC) of xenon is unknown in any neonatal species. Methods Eight newborn pigs were anaesthetised with sevoflurane alone and then sevoflurane plus xenon at two temperatures. Pigs were randomised to start at either 38.5°C or 33.5°C. MAC for sevoflurane was determined using the claw clamp technique at the preset body temperature. For xenon MAC determination, a background of 0.5 MAC sevoflurane was used, and 60% xenon added to the gas mixture. The relationship between sevoflurane and xenon MAC is assumed to be additive. Xenon concentrations were changed in 5% steps until a positive clamp reaction was noted. Pigs' temperature was changed to the second target, and two MAC determinations for sevoflurane and 0.5 MAC sevoflurane plus xenon were repeated. Results MAC for sevoflurane was 4.1% [95% confidence interval (CI): 3.65-4.50] at 38.5°C and 3.05% (CI: 2.63-3.48) at 33.5°C, a significant reduction. MAC for xenon was 120% at 38.5°C and 116% at 33.5°C, not different. Conclusion In newborn swine sevoflurane, MAC was temperature dependent, while xenon MAC was independent of temperature. There was large individual variability in xenon MAC, from 60% to 120%.

Background Morbid obesity is associated with important differences in pharmacokinetics and pharmacodynamics. The aim of this study was to determine minimum alveolar concentration of sevoflurane for maintaining bispectral index (BIS) below 50 (MACBIS50) in morbidly obese patients undergoing bariatric surgery using the Continual Reassessment Method (CRM) method. Methods Twenty-four morbidly obese patients (body mass index 40–70 kg/m2) were enrolled in our study. Twenty minutes following pre-medication with fentanyl 100 μg, general anaesthesia was induced using propofol 2 mg/kg and cisatracurium 2 mg/kg to facilitate tracheal intubation. The lowest BIS score was recorded following induction. Thereafter, when BIS began to increase > 60, maintenance of anaesthesia was started with a pre-determined end-tidal sevoflurane concentration (ETSevo) and maintained for 10 min followed by 1-min assessment of BIS taken at 10-s intervals to determine the ETSevo. The ETSevo leading to a probability close to 80% success was calculated using the CRM, and the MACBIS50 leading to 50% success was calculated by fitting the data to a dose-probability sigmoid curve, respectively. Results The ETSevo able to maintain BIS value below 50 was 1.8% in 67% [95% confidence interval (CI) 0.44–0.86] and higher in the remaining 33% of the patients and the ETSevo leading to a BIS value below 50 in 50% of the patients (MACBIS50) was 1.6 ± 0.10%. Conclusions The calculated values (1.8% and 1.6%) were higher than that previously reported in normal adult patients (0.97%; 95% CI 0.89–1.1%) and less than that reported in children (2.8%; 95% CI 2.7–3.1%).

Background Non-steroidal anti-inflammatory drugs are analgesics commonly used for post-operative pain. However, their effect on dosages of inhaled anesthetics during surgery is unclear. We investigated the effect of flurbiprofen axetil and parecoxib sodium on the minimum alveolar concentration of sevoflurane required to blunt stress responses to skin incision under general anesthesia. Methods One hundred and five adult patients were randomly allocated to four treatment groups, each receiving sevoflurane: control (sevoflurane only), lidocaine (1 mg/kg bolus, followed by continuous infusion of 20 μg/kg/min after intubation), Intravenous (IV) flurbiprofen (1 mg/kg before skin incision), and IV parecoxib (40 mg before skin incision). Following anesthetic induction and stabilization of end-tidal sevoflurane concentration, mean arterial blood pressure and heart rate were recorded 2 min before and at 5-min intervals after skin incision. The stable end-tidal sevoflurane concentration was calculated using an up-and-down method. Results The minimum alveolar concentration of sevoflurane required to blunt the stress responses to skin incision in the control, lidocaine, flurbiprofen, and parecoxib groups was 4.63 ± 0.08%, 2.67 ± 0.08%, 3.33 ± 0.08%, and 3.80 ± 0.11%, respectively. These figures for the later three groups were all significantly less than that of the control group (P = 0.021, P = 0.037, and P = 0.011, respectively); that of the flurbiprofen group was significantly less than the parecoxib (P = 0.034). Conclusion The non-steroidal anti-inflammatory drugs flurbiprofen axetil and parecoxib sodium decreased the minimum alveolar concentration of sevoflurane required to blunt the stress response to skin incision during general anesthesia.

Background We investigated the cardioprotective effects of isoflurane administered at the onset of reperfusion in senescent rat in vivo, and the activation of the reperfusion injury salvage kinase (RISK) pathway to address a possible mechanism underlying age-related differences. Methods Male Wistar rats were assigned to age groups (young, 3–5 months; old, 20–24 months), and randomly selected to receive isoflurane (1 minimum alveolar concentration) or not for 3 min before and 2 min after reperfusion (ISO postC). Rats were subjected to coronary occlusion for 30 min followed by 2 h of reperfusion. Western blot analysis was used to assess the phosphorylation of extracellular signal-regulated kinase (ERK1/2), Akt, and GSK3β 15 min after reperfusion. Results Brief administration of isoflurane 3 min before and 2 min after the initiation of early reperfusion reduced infarct size (56 ± 8% of left ventricular area at risk, mean ± standard deviation) compared with controls (68 ± 4%) in young rats, but had no effect in old rats (56 ± 8% in ISO postC and 56 ± 10% in control, respectively). Phosphorylation of ERK1/2, Akt, and GSK3β were increased in the young ISO postC group but not in the old ISO postC group compared with control groups of the respective ages. Conclusions We demonstrated that isoflurane post-conditions the heart in young but not in senescent rats. Failure to activate RISK pathway may contribute to attenuation of isoflurane-induced post-conditioning effect in senescent rats.

Background Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase. Methods Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10??g/g intraperitoneally) or its vehicle dimethy sulfoxide (10??l/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18?min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-BadSer112 and B-cell lymphoma 2 was determined using Western immunoblotting analysis. Results Infarct size in control animals (CON) was 46?±?3%. Dimethylsulfoxide (47?±?3%) and Pim-1 kinase inhibitor II (44?±?5%) did not significantly reduce infarct size. Desflurane (16?±?2%*; *P? Conclusion These data suggest that Pim-1 kinase mediates both desflurane-induced postconditioning and IPOST in mice.

Background We tested the hypothesis that an upregulation of antioxidant proteins [Cu-Zn superoxide dismutase (SOD), Mn SOD, catalase, glutathione peroxidase, and glutathione peroxidase] plays a role in the delayed protection against myocardial stunning produced by isoflurane preconditioning (ISOPC). Findings were compared with late ischemic PC (IPC). Methods Fourteen mongrel dogs were chronically instrumented to measure coronary blood flow and myocardial wall thickening (WT) in conscious state. In Group 1, dogs underwent IPC, induced by a 10-min coronary artery occlusion (CAO); after 24 h of reperfusion, they were subjected to a second 10-min ischemia CAO-reperfusion. In Group 2 (ISOPC), dogs inhaled one minimum alveolar concentration (MAC) ISO (1.4% in O2) for 60 min, allowed to recover for 24 h, and then subjected to CAO ischemia-reperfusion. Recovery of WT following the initial 10-min CAO in Group 1 served as control response for both ISOPC and IPC. Expression and activity of antioxidant proteins were measured using Western blotting and spectrophotometric techniques, respectively. Results Two to three hours of reperfusion were required for recovery of WT following either ISOPC or IPC; in contrast, without PC, WT remained markedly reduced (30% below baseline) at this time point and required more than 6 h of reperfusion for recovery. Neither IPC nor ISOPC affected expression of Cu-Zn SOD, Mn SOD, or catalase. However, ISOPC increased activity of Mn SOD (+40%), catalase (+39%), glutathione peroxidase (+37%), and glutathione reductase (+93%) (P

Background: The immunomodulatory effects of volatile anaesthetics in vitro and the protective effect of propofol in lung injury spurred us to study the effects of volatile anaesthetics and propofol on lung tissue in vivo. Methods: Twenty-seven pigs were randomized to 4-h general anaesthesia with propofol (8 mg/kg/h, group P, n=9), sevoflurane [minimum alveolar concentration (MAC)=1.0, group S, n=9) or desflurane (MAC=1.0, group D, n=9). Four healthy animals served as the no-ventilation group. Bronchoalveolar lavage fluid (BALF) was obtained to measure the cell counts, platelet-activating factor acetylhydrolase (PAF-AcH), phospholipase A2 (PLA2) and superoxide dismutase (SOD) activity. Lung tissues were evaluated histologically and for caspase-3 expression. Results: Volatile anaesthetics reduced PAF-AcH levels without affecting PLA2 activity and resulted in decreased alveolar macrophage and increased lymphocyte counts in BALF (sevoflurane: 29 ± 23%; desflurane: 26 ± 6%, both P

Background: The aim of this study was to investigate whether sevoflurane-induced post-conditioning has a neuroprotective effect against incomplete cerebral ischemia in rats. Methods: After cerebral ischemia by right common carotid artery occlusion in combination with hemorrhagic hypotension (35 mmHg) for 30 min, 1.0 minimum alveolar concentration of sevoflurane was administered for 15 min (Post-C 15, n=8), 30 min (Post-C 30, n=8), or 60 min (Post-C 60, n=8) in rats. Sevoflurane was not administered in control (n=8) and sham control rats (n=8). Neurologic evaluations were performed at 24, 48, and 72 h after ischemia. Degrees of neuronal damage in ischemic hippocampal CA1 and the cortex were assessed by counting eosinophilic neurons, and detection of DNA fragmentation was performed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Results: Neurologic deficit scores in the Post-C 60 group were higher than in the control group at 48 and 72 h post-ischemia (P

Background and objectives The mitochondrial membrane potential (DeltaPsi(m)) drives the three fundamental functions of mitochondria, namely adenosine triphosphate (ATP) generation, Ca(2+) uptake/storage, and generation/detoxification of ROS. Isoflurane depolarizes neural mitochondria. The sensitivity for general anesthetics increases with age, but the mechanism for this age-related sensitivity is still unknown. We compared the effect of isoflurane on [Ca(2+)](i) and DeltaPsi(m) in isolated pre-synaptic terminals (synaptosomes) from neonatal, adolescent, and adult rats and the influence of interventions in the respiratory chain was assessed. Methods Synaptosomes were loaded with the fluorescent probes fura-2 ([Ca(2+)](i)) and JC-1 (DeltaPsi(m)) and exposed to isoflurane 1 and 2 minimum alveolar concentration (MAC). The effect on the electron transport chain was investigated by blocking complexes I and V. Results In neonatal rats isoflurane had no significant effect on DeltaPsi(m). In adolescent and adult synaptosomes, however, isoflurane 1 and 2 MAC decreased DeltaPsi(m). Isoflurane 2 MAC increased [Ca(2+)](i) in neonatal and adolescent rats, but not in adult synaptosomes. In Ca(2+)-depleted medium, isoflurane still decreased DeltaPsi(m), while [Ca(2+)](i) remained unaltered. By blocking complex V of the respiratory chain, the isoflurane-induced mitochondrial depolarization was enhanced in all age groups. Blocking complex I depolarized the mitochondria to the same extent as isoflurane 2 MAC, but without any additive effect. Conclusions The depolarizing effect of isoflurane on neural mitochondria is more pronounced in the adolescent and adult than in neonatal synaptosomes. The increased mitochondrial sensitivity with age seems to be related to the reversed function of the ATP synthase of the electron transport chain.

Background: Right ventricular (RV) function is an important determinant of post-operative outcome. Consequences of RV infarction might be limited by pre-conditioning with volatile anesthetic drugs. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of isoflurane and xenon on the extent and degree of myocardial injury. Methods: IR injury was induced by a 90-min ligation of the distal right coronary artery and 120-min reperfusion in thiopental anesthetized pigs. A control group (n=12) was compared with two groups, which received either 0.55 minimum alveolar concentration (MAC) isoflurane (n=10) or xenon (n=12) starting 60 min before ischemia. Myocardial injury was described by three criteria: the infarct size related to area at risk (IS/AAR), the infiltration of neutrophils as determined by myeloperoxidase (MPO) activity, and the plasma levels of tumor necrosis factor α (TNFα), interlukin 6 (IL-6), myoglobin and troponin-T (TnT). Results: IS/AAR was reduced from 58.3±6.2% in the control group to 41.8±7.8% after isoflurane and 42.7±8.5% after xenon pre-treatment, which equals an absolute reduction of 16.5% [95% confidence interval (CI): 10.9–22.1] and 15.5% (95% CI: 10.1–20.9). The maximum increase of TnT could be observed within the xenon group. Both treatment groups were characterized by lower MPO activity, in the infarct and periinfarct region and lower plasma concentrations of TNFα and IL-6. Conclusions: It could be demonstrated for the first time in a model of RV infarction that the continuous application of isoflurane or xenon before, during and after ischemia reduced the extent (size) and severity (inflammation) of myocardial injury.

Background: In contrast to other volatile anesthetics, xenon produces less cardiovascular depression with fewer fluctuations of various hemodynamic parameters, but reduces cardiac output (CO) in vivo. Besides an increase in left ventricular afterload and reduction of heart rate, an impairment of the right ventricular function might be an additional pathophysiological mechanism for the reduction of CO. Therefore, we used an animal model to study the effects of xenon as a supplemental anesthetic on right ventricular function, especially right ventricular afterload. Methods: Right ventricular function was monitored with a volumetric pulmonary artery catheter in 11 pigs during general anesthesia with thiopental. Six animals received additional 70% (volume) xenon (equivalent to 0.55 MAC minimum alveolar concentration). Parameters for systolic function, afterload, and preload were calculated at baseline and during 50 min of xenon application, and in a corresponding control group. Significant differences were detected by multivariate analyses of variance for repeated measures. Results: Xenon reduced CO on average by 30% and increased pulmonary arterial elastance by 60%, which led to a reduction of the right ventricular ejection fraction by 25%. Whereas right ventricular preload remained stable, maximal slope of pulmonary artery pressure and the right ventricular elastance increased. No effect on the ratio of stroke work and end-diastolic volume was found. Conclusion: The reduction in CO during xenon anesthesia was partly due to an impairment of the right ventricular function, mainly caused by an increased afterload, without an impairment of systolic ventricular function.

Background: Even small costs per case can become economically significant in high volume day surgical units. While general anaesthesia with higher fresh gas flow rates has technical advantages, they result in higher costs. The aim of the present study was to evaluate drug consumption and direct costs related to variations in the fresh gas flow and use of nitrous oxide at a 1 minimum alveolar concentration (MAC) sevoflurane end-tidal anaesthesia for day surgery. Methods: Thirty-two ASA I–II patients undergoing elective day surgery under general anaesthesia [14 (10–21) min] were studied. Induction was with propofol and fentanyl 100 μg. After laryngeal mask airway placement, patients were randomized to one of four different fresh gas flows: 1 or 2 l/min oxygen in air (50% oxygen), 3 l/min (33% oxygen), or 3 l/min oxygen in nitrous oxide (33% oxygen). Anaesthesia was maintained at 1 MAC. The vaporizer was weighed before and after each procedure. The primary study variable was the sevoflurane utilization per minute. Results: Sevoflurane utilization increased with increasing fresh gas flow for oxygen in air (r2= 0.89). The nitrous oxide in oxygen group had the lowest sevoflurane utilization, even compared with the lowest oxygen in air group (0.36 vs. 0.48 g/min). Conclusion: Sevoflurane utilization during 1 MAC anaesthesia increases linearly with fresh gas flow and is still higher than when nitrous oxide is used even with very low fresh gas flow rates. Direct inhaled anaesthesia-related costs are consequently 20% higher than when nitrous oxide is used, even for the lowest oxygen in air fresh gas flows.

Background We examined the hypothesis that the minimum alveolar concentration of desflurane for maintaining bispectral index (BIS) below 50 (MACBIS50) decreases with advance of age. Methods Sixty young (20–30 year), middle-aged (31–65 year) and elderly (66–80 year) patients were included (n = 20, each group). Five minutes following the start of continuous intravenous administration of remifentanil at 0.25 μg/kg/min, general anaesthesia was induced with propofol 2 mg/kg and rocuronium 0.8 mg/kg to facilitate tracheal intubation. Infusion of remifentanil was stopped immediately after tracheal intubation. When BIS began to increase > 60, maintenance of anaesthesia was started with an end-tidal desflurane concentration of 4.0% and maintained for 10 min followed by 1-min assessment of BIS taken at 10-s intervals. MACBIS50 of each age group was estimated by up–down methodology. Results MACBIS50 of desflurane in young, middle-aged and elderly patients was 4.25% end-tidal (95% confidence intervals 4.04–4.46), 3.58% (3.38–3.79) and 2.75% (2.50–3.00) respectively. MACBIS50 was higher (P = 0.011) in young patients and lower (P = 0.012) in elderly patients than those in middle-aged patients. Conclusions Advance in age significantly decreased the concentrations of desflurane required to maintain BIS below 50. BIS reflected age-associated decrease in end-tidal concentrations of desflurane required for maintaining adequate depth of anaesthesia during resting state.

Background: Bronchoactive properties of volatile agents against lung constriction are well established. The purpose of this study was to investigate the ability of halothane (Hal), isoflurane (Iso), sevoflurane (Sev) and desflurane (Des) to alter the lung mechanics in the absence of an airway tone and during acetylcholine (Ach)-induced bronchoconstriction. Methods: Low-frequency pulmonary impedance data (ZL) were collected from isolated, normo-perfused rat lungs under baseline conditions and following the injection of Ach (0.1 mg/kg) into the pulmonary artery. Measurements were performed without the administration of any anaesthetic agent in the first phase of the experiments and during inhalation without any volatile agent (control group, n = 6) or during inhalation of Hal (n = 6), Iso (n = 9), Sev (n = 6) or Des (n = 8) at 1 minimum alveolar concentration (MAC). The airway resistance (Raw) and parenchymal damping and elastance were estimated from the ZL data by model fitting. Results: Under baseline conditions, the basic value of Raw was significantly decreased by Des (− 31.2 ± 3.8%) and Sev (− 18.0 ± 4.5%) administration, whereas Hal and Iso did not have a statistically significant effect on Raw (− 3.3 ± 5.1% and − 8.6 ± 2.4%, respectively). Moreover, all four inhalation anaesthetics prevented the increase in Raw following Ach administration, the findings ranging between − 14.3 ± 11.4% for Hal and − 37.5 ± 10.9% for Sev. Conclusions: Our results on a denervated isolated perfused lung model demonstrate the potential of Des and Sev to decrease the basal airway tone, whereas Iso and Hal are ineffective in this regard. All of these volatile agents markedly protect against Ach-induced bronchoconstriction.

Background: In this study, we investigated the inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated human myometrium. Methods: Following delivery of the infant and placenta, a small segment of myometrium was excised from the upper incisional surface of the lower uterine segment and 20 strips, randomly assigned into two groups (n = 10), were obtained from 20 non-laboring term parturients. The study protocol consisted of a 60-min period of spontaneous contractions, control recording with oxytocin 2 × 109 m (10-min period), washout interval of 10 min, volatile administration (three times per 15-min period) of 0.5, 1 and 2 minimum alveolar concentration (MAC), response to oxytocin (10-min period), a further washout interval (10-min period) and subsequent control recording with oxytocin without anesthetics. Results: After oxytocin administration, the frequency and amplitude of contractions increased (P

Background: Isoflurane and halothane act in the spinal cord to blunt ascending transmission of impulses to the brain resulting from noxious stimulation. Because intrathecal picrotoxin (an antagonist at the gamma-aminobutyric acid-A receptor) partially reverses the immobilizing effect of isoflurane and halothane, we hypothesized that the electroencephalographic response to noxious stimulation would likewise be partially reversed by intrathecal picrotoxin. Methods: Rats were anesthetized with isoflurane (n = 8) or halothane (n = 8) and a laminectomy performed. Following determination of minimum alveolar concentration (MAC), the electroencephalogram (EEG) was recorded during separate applications of a hindpaw clamp, tail clamp and electrical current to the tail at 0.8 and 1.2 MAC. Picrotoxin was then applied to the exposed spinal cord and the EEG response to noxious stimulation again determined. Results: The EEG was more active during halothane anesthesia than isoflurane (spectral edge frequency for 95% power: 25.6 ± 2.1 Hz vs. 23.1 ± 1.6 Hz, P

Background: The effects of isoflurane and halothane anesthesia on hepatic circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, in an attempt to assess which of the anesthetics was the better one for hepatic resection. Methods: Mongrel dogs (n=24) were divided into two groups and accordingly anesthetized with isoflurane (n=12) or halothane (n=12). Each test anesthetic was administered in air. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows 1) before the inhalation of each anesthetic (baseline); 2) 1 h inhalation of 1.5 MAC (minimum alveolar concentration) of each anesthetic; and 3) 1 h after hepatolobectomy with each anesthesia. Measurements of systemic hemodynamics, blood gas tensions, and the arterial ketone body ratio were made at the same time. Results: Isoflurane maintained portal venous, hepatic arterial and total hepatic blood flows better than halothane anesthesia before and after hepatolobectomy. With halothane anesthesia, hepatolobectomy decreased prominently hepatic arterial blood flow. Hepatic arterial and mesenteric vascular resistance increased in the halothane group, but remained constant in the isoflurane group after hepatolobectomy. Hepatic oxygen delivery was significantly suppressed in the halothane group, but did not change in the isoflurane group. No significant difference was found in hepatic oxygen consumption between the two groups, but the arterial ketone body ratio decreased significantly only in the halothane group before and after hepatolobectomy. Conclusion: The present data indicate that isoflurane has less adverse effect than halothane anesthesia on hepatic circulation, oxygen delivery and energy charge in hepatolobectomy cases.

BACKGROUND Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.

Background: Xenon is an odorless gas with low blood-gas solubility coefficient and without occupational and environmental hazards. This investigation was performed to evaluate the speed of induction, and respiratory and cardiovascular reactions to inhalation induction with xenon compared to an equianesthetic concentration of sevoflurane. Results: Compared to equianesthetic sevoflurane, xenon produced a faster induction of anesthesia (14759 versus 71221 s, respectively) with smaller decreases in respiratory rate, tidal volume and minute ventilation. Both agents showed comparable cardiovascular stability and oxygen saturation during induction. One patient in the sevoflurane group had breath-holding and movements of extremities and another had only breath-holding. No patients in the xenon group experienced any complications. Conclusion: Xenon produced a faster induction of anesthesia without any complications than sevoflurane. Xenon had smaller decreases in tidal volume and respiratory rate during induction than sevoflurane. Xenon might offer an alternative to sevoflurane for an inhalation induction. Method Twenty-four adult ASA 1–2 patients premedicated with 0.05 mg/kg of midazolam were instructed to take vital capacity breaths of 1 minimum alveolar concentration (MAC) of either xenon or sevoflurane until they lost consciousness. Induction time, total ventilatory volume, tidal volume, respiratory rate, minute ventilation, end-tidal MAC fraction, cardiovascular parameters and oxygen saturation were recorded. The patients were interviewed on the following day to evaluate their acceptability rating of the inhalation inductions.

Background : Volatile anaesthetics have a direct inhibitory effect upon epicardial coronary arterial smooth muscles (1-4). The site and mode of their action at the cellular level need to be clarified, which was the purpose of our study. The present investigation attempted to answer the question in what way volatile anaesthetics influence Ca 2+ -related contraction in isolated porcine epicardial coronary to understand their intracellular mechanism. Methods : Isolated helical strips of porcine epicardial coronary artery without endothelium were suspended for isotonic contraction recordings in Krebs-Ringer's solution. 9.4x10 -2 M K+, 2.5x10 -3 M Ca 2+ -induced shortening of the strips was regarded as the reference value (100%). After incubation in Ca 2+ -free solution with 10 -3 M ethlene glycol bis (β-aminoethyl ether)-N,N-tetraacetic acid (EGTA) for 60 minutes, the muscle strips were exposed to increasing Ca 2+ concentrations (10 4 -10 -2 ) either in the presence or absence of 1.5 or 2.5 minimum alveolar concentration (MAC) halothane, isoflurane or sevoflurane, with 9.4x10 -2 M K + bath solution. Results : All three drug groups produced apparent biphasic effects with a cumulative increase of Ca 2+ concentration compared with control groups. An initial increase at low Ca 2+ concentration was followed by a decrease of Ca 2+ -activated contractions. Isoflurane affected Ca 2+ -induced contraction significantly more than halothane and sevoflurane. Conclusions : The results imply that volatile anaesthetics influence Ca 2+ -dependent activity of coronary smooth muscle by complex mechanisms, which involve promotion of intracellular Ca 2+ release and other mechanisms that alter sensitivity to calcium.

Background: We studied the inhibitory effects of desflurane and sevoflurane on oxytocin-induced contractions of isolated gravid rat myometrium. Methods: Twenty strips were obtained from rats and these were randomly assigned into two groups. The effects of desflurane and sevoflurane were evaluated by treating strips with oxytocin alone 2×10−9 M or with oxytocin after desflurane and sevoflurane at 0.5, 1, and 2 MAC. Results: Oxytocin significantly increased the amplitude and duration of contractions (P

Background: The precise mechanism by which sevoflurane exerts its effects in the human brain remains unknown. In the present study, we quantified the effects of sevoflurane on regional cerebral glucose metabolism (rGMR) in the human brain measured with positron emission tomography. Methods: Eight volunteers underwent two dynamic 18F-fluorodeoxyglucose positron emission tomography (PET) scans. One scan assessed conscious-baseline metabolism and the other scan assessed metabolism during 1 minimum alveolar concentration (MAC) sevoflurane anaesthesia. Cardiovascular and respiratory parameters were monitored and bispectral index responses were registered. Statistical parametric maps and conventional regions of interest analysis were used to determine rGMR differences. Results: All subjects were unconsciousness at 1.0 MAC sevoflurane. Cardiovascular and respiratory parameters were constant over time. In the awake state, rGMR ranged from 0.24 to 0.35 μmol/g/min in the selected regions. Compared with the conscious state, total GMR decreased 56% in sevoflurane anaesthesia. In white and grey matter, GMR was averaged 42% and 58% of normal, respectively. Sevoflurane reduced the absolute rGMR in all selected areas by 48–71% of the baseline (P≤0.01), with the most significant reductions in the lingual gyrus (71%), occipital lobe in general (68%) and thalamus (63%). No increases in rGMR were observed. Conclusions: Sevoflurane caused a global whole-brain metabolic reduction of GMR in all regions of the human brain, with the most marked metabolic suppression in the lingual gyrus, thalamus and occipital lobe.

The azeotropic mixture of halothane and diethyl ether (HE) may be a valuable alternative to other anaesthetic agents under circumstances such as war, civil disaster, and primitive conditions. In the present study the minimum alveolar concentrations (MACs) for HE in man (n = 25) and in pigs (n = 6) were determined. For comparison with results of other studies, the MAC for halothane in man (n = 14) was also determined. A Normac gas analyser and a Varian 3700 gas chromatograph were calibrated against known standards of HE. The performance of two vaporizers (Fluotec Mark III, Servo vaporizer for halothane) was studied. The Fluotec Mark III vaporizer and the Servo halothane vaporizer filled with HE gave a linear performance with increasing dial settings. The Normac gas analyser set for methoxyflurane was linearly sensitive to the ether component of the azeotrope. The MAC for HE in man was 0.71 vol.% +/- 0.03 (s.e.mean) (ether 0.21 vol.%, halothane 0.50 vol.%) in the age group 19-42 years. MAC for halothane in man was 0.65 +/- 0.03 in the age group 19-32 years. The MAC for HE in pigs between 20-24 kg was 0.99 vol.% +/- 0.07. The ether component seems to act synergistically with halothane in the azeotropic mixture. The present study provides an opportunity to compare HE with other volatile anaesthetic agents.

BACKGROUND Sevoflurane has been shown to have different effects on cerebrovascular CO(2) reactivity in comparison with isoflurane. In this study, the comparative effects of sevoflurane vs. isoflurane on cerebrovascular CO(2) reactivity were examined in patients with hypertension. METHODS Fifty patients, 30 hypertensive and 20 normotensive, were included in this study. The 30 hypertensive patients were divided into two groups: sevoflurane and isoflurane. Patients with controlled hypertension (n= 9 in each of the two groups) were those with normal blood pressure levels (systolic blood pressure below 139 mmHg). Patients with uncontrolled hypertension (n= 6 in each of the two groups) were those with high blood pressure levels despite medication (systolic blood pressure above 160 mmHg). Anesthesia was maintained with either 1.0 minimum alveolar concentration (MAC) of sevoflurane or 1.0 MAC of isoflurane in 33% oxygen and 67% nitrous oxide. A 2.5-MHz pulsed transcranial Doppler probe was attached to the patient's head at the right temporal window for continuous measurement of the mean blood flow velocity in the middle cerebral artery (V(mca)). After establishing baseline values of V(mca) and cardiovascular hemodynamics, the end-tidal CO(2) was increased by decreasing the ventilatory frequency by 2-5 breaths per minute. RESULTS Values of the absolute and relative CO(2) reactivity in the sevoflurane groups were lower than those in the isoflurane groups. There were no significant intra-group differences in the absolute and relative CO(2) reactivity within the sevoflurane and isoflurane groups. CONCLUSIONS Our findings suggest that, in hypertensive patients, the control of cerebral blood flow by altering the pressure of arterial CO(2) (P(a)co(2)) can be more effectively achieved during isoflurane rather than sevoflurane anesthesia.

Background: Recent studies suggest that volatile anaesthetics have anti-inflammatory and preconditioning properties and that beta-adrenoceptors are involved in the signalling pathways for these effects. Concurrently, the blockade of beta-adrenoceptors has been shown to augment the release of inflammatory mediators in response to pro-inflammatory stimuli. We therefore aimed to investigate whether the beta-adrenoceptor antagonist propranolol might modulate the anti-inflammatory effects of isoflurane on the systemic and pulmonary release of pro-inflammatory cytokines in endotoxemic rats. Methods: Forty anaesthetized and ventilated Sprague–Dawley rats were randomly treated as follows. Lipopolysaccharide (LPS) only (n = 8), endotoxemia with LPS [5 mg/kg, intravenously (i.v.)]. LPS-isoflurane (n = 8): endotoxemia and continuous inhalation of 1 minimum alveolar concentration (MAC) of isoflurane. LPS-isoflurane-propranolol (n = 8): administration of propranolol (3 mg/kg) before continuous inhalation of isoflurane and induction of endotoxemia. LPS-propranolol (n = 8): administration of propranolol (3 mg/kg) before endotoxemia without inhalation of isoflurane. Sham (n = 8): control-group only with surgical preparation. After 4 h of endotoxemia, levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in plasma and bronchoalveolar fluid (BALF) were analysed. Release of nitric oxide (NO) and amount of inducible nitric oxide synthase (iNOS) protein in alveolar macrophages was measured by Griess assay or determined by Western Blotting, respectively. Results: Inhalation of isoflurane reduced the release of TNF-α (P

The brain is a complex organ and critically dependent on its oxygen metabolism and blood supply. The purpose of the present study was twofold: firstly to design, evaluate, and adopt a physiologically stable experimental model for repeated measurements of cerebral cortical microvascular perfusion by a new laser Doppler technique (experimental part (I) - intrinsic model). Secondly, to examine the complication rates of a brief period of hypothermia for protection of the brain in patients who were operated on for subarachnoid aneurysms (clinical part (II) - extrinsic model).Method. Part I. In contrast to conventional laser Doppler flowmetry, the laser Doppler perfusion imager (LDPI) creates a two-dimensional map of the tissue perfusion in an area of up to 120 x 120 mm, comprising 4096 measurement points. Measurements were made in a closed cranial window in ventilated anaesthetised pigs (n=25). Provocations that altered cerebral blood flow (CBF) were those that can occur during anaesthesia and critical care, including varying arterial concentration of carbon dioxide and mean arterial blood pressure (MABP), and those caused by different types (isoflurane and sevoflurane) and concentrations (minimum alveolar concentration, MAC, 0.3-1.2) of volatile anaesthetics.Part II. The feasibility and complication rates of rapidly-induced moderate hypothermia in 359 operations were examined prospectively. The complications that we sought were: altered haemostasis, infections, haemodynamic instability, and increased need for postoperative ventilatory support. Hypothermia was produced by cold (4°C) intravenous infusions and convective cooling. This lowered the body temperature at a mean (SD) 4 (0.4)oC h1 to 32.5 (0.4)oC. The body temperature returned to normal in all patients by 5 (2) hours postoperatively.Results. Part I. Cortical CBF was distributed highly heterogeneously and it was strongly dependent on MABP, as well as concentrations of CO2 During decreasing MABP the lower limit of autoregulation varied locally in the cortex and the 'classic' autoregulatory pressure-flow relation was present in only a few areas. Alterations in PaC02 concentration did not affect the pressure-flow relation at low perfusion pressures, whereas at normal or above normal values, hypercapnia increased CBF considerably (p < 0.001). CBF was not affected by the anaesthetic (isoflurane or sevoflurane) or dose (MAC 0.3-1.2) used.Part II. Perioperative and postoperative complications itcluded: circulatory instability (10%), arrhythmias (5%), abnormalities of coagulation, need for blood transfusions (47%), infections (8%), and puhnonary complications including infiltrates or oedema while on ventilatory support (27%). There was no correlation between the extent of hypothermia and any of the complications. However, there was a strong correlation (p < 0.001) between the incidence of complications and the severity of the underlying neurological disease as assessed by the Hunt and Hess score.Conclusion Part I. The LDPI method was useful and relevant for measurement of cortical CBF in this experimental model. 'Classic' autoregulatory patterns were found only when all values sampled wereclustered together, whereas the autoregulatory capacity is often lacking at the local level in the cortex. Volatile anaesthestics (isoflurane and sevoflurane) in the doses 0.3 - 1.2 (MAC) did not affect the regulation of CBF in this model. Part II. Moderate hypothermia can be achieved within 1 hour of induction of anaesthesia and seems to be safe as far as the risks of perioperative and postoperative complications are concerned.

Background The mitochondrial membrane potential (DeltaPsim) controls the generation of adenosine triphosphate (ATP) and reactive oxygen species, and sequesteration of intracellular Ca2+[Ca2+]i. Clinical concentrations of sevoflurane affect the DeltaPsim in neural mitochondria, but the mechanisms remain elusive. The aim of the present study was to compare the effect of isoflurane and sevoflurane on DeltaPsim in rat pre-synaptic terminals (synaptosomes), and to investigate whether these agents affect DeltaPsim by inhibiting the respiratory chain. Methods Synaptosomes were loaded with the fluorescent probes JC-1 (DeltaPsim) and Fura-2 ([Ca2+]i) and exposed to isoflurane or sevoflurane. The effect of the anaesthetics on the electron transport chain was investigated by blocking complex I and complex V. Results Isoflurane 1 and 2 minimum alveolar concentration (MAC) decreased the normalized JC-1 ratio from 0.92 +/- 0.03 in control to 0.86 +/- 0.02 and 0.81 +/- 0.01, respectively, reflecting a depolarization of the mitochondrial membrane (n = 9). Isoflurane 2 MAC increased [Ca2+]i. In Ca2+-depleted medium, isoflurane still decreased DeltaPsim while [Ca2+]i remained unaltered. The effect of isoflurane was more pronounced than for sevoflurane. Blocking complex V of the respiratory chain enhanced the isoflurane- and sevoflurane-induced mitochondrial depolarization, whereas blocking complex I and V decreased DeltaPsim to the same extent in control, isoflurane and sevoflurane experiments. Conclusions Isoflurane and sevoflurane may act as metabolic inhibitors by depolarizing pre-synaptic mitochondria through inhibition of the electron transport chain, although isoflurane seems to inhibit mitochondrial function more significantly than sevoflurane. Both agents inhibit the respiratory chain sufficiently to cause ATP synthase reversal.

Background: One advantage of tracheal extubation during deep anaesthesia is that respiratory complications are reduced. Sevoflurane is a suitable anaesthetic agent for children. This study was conducted to determine the minimum alveolar concentration of sevoflurane required to prevent cough or movement during and after tracheal extubation (MACextubation). Methods: We studied 30 nonpremedicated children, aged 2–10 yr, undergoing plastic surgery. They were allocated randomly to five groups (end-tidal sevoflurane concentrations: 2.0, 2.5, 3.0, 3.5, 4.0%). After surgery, 60% nitrous oxide was discontinued and the target concentration of sevoflurane was maintained for at least 10 min in 100% oxygen, then the trachea was extubated to determine MACextubation. Logistic regression was used to estimate MACextubation. of sevoflurane. Results: MACextubation. was 2.3 (0.2; standard error)% (95% confidence limits: 1.2% and 2.7%). Conclusions: Tracheal extubation in 50% of anaesthetized children age 2–10 yr may be accomplished without coughing or moving at 2.3% end-tidal concentration of sevoflurane.

Background: Nociceptin is the endogenous agonist of the opioid receptor-like (ORL) 1 receptor (NOP), and both nociceptin and NOP are widely expressed in the brain and spinal cord, which are target organs of general anaesthetics. As nociceptin has been reported to be involved in modulating pain mechanisms and stress responses, it is possible that the activity of the nociceptin system affects the anaesthetic potency of general anaesthetics. To address this possibility, we investigated the minimum alveolar concentrations (MACs) of various volatile anaesthetics in nociceptin receptor knockout mice (NOP–/–) and wild-type mice (NOP+/+). Methods: We used male NOP–/– mice and NOP+/+ mice. MACs for halothane, isoflurane and sevoflurane were determined by the tail-clamp method. Results: MACs for halothane, isoflurane and sevoflurane in NOP–/– mice were 1.60 (SD 0.06), 1.68 (0.08) and 3.36 (0.07)%, respectively. In NOP+/+ mice, MACs for halothane, isoflurane and sevoflurane were 1.59 (SD 0.07), 1.72 (0.07) and 3.38 (0.09)%, respectively. Conclusion: MACs in NOP–/– mice did not significantly differ from those in NOP+/+ mice for halothane, isoflurane and sevoflurane. This result suggests that the nociceptin system does not affect the anaesthetic potency of volatile anaesthetics.

BACKGROUND Halothane and isoflurane are frequently used in studies of perinatal hypoxia and ischemia. Little information exists on the minimum alveolar concentration (MAC) necessary to prevent movement to a painful stimulus in newborn pigs and no information on the effects of hypothermia on MAC in pigs. Hypothermia is currently investigated as a posthypoxic neuroprotective intervention. METHODS The MAC of halothane and isoflurane necessary to prevent movement when a 25 cm hemostatic clamp was applied to the tail were determined in six 20-48-hour-old piglets, and when the same stimulus was applied to the hoof. MAC for halothane was first determined at 39 degrees C, then at 35 degrees C, whereafter halothane was discontinued and MAC for isoflurane determined first at 35 degrees C and then at 39 degrees C. RESULTS In all six piglets MAC was lower at 35 degrees C than at 39 degrees C for both anesthetics with both tail and hoof determination, lower for halothane than isoflurane for both stimuli at both temperatures, and lower for tail than hoof determination for both anesthetics at both temperatures. For halothane at 39 degrees C, mean (SD) MAC hoof was 0.82 (0.05)% vs tail 0.60 (0.12)%, and at 35 degrees C, hoof 0.65 (0.06)% vs tail 0.42 (0.10)%. For isoflurane at 39 degrees C, MAC hoof was 2.47 (0.28)% vs tail 1.83 (0.28)%, and at 35 degrees C, hoof was 1.83 (0.18)% vs tail 0.85 (0.25)%. CONCLUSION In the newborn piglet, MAC should be determined by hoof clamp, MAC of isoflurane is approximately three times that of halothane, and both are reduced during hypothermia.

Requirements for a safe standard for anaesthesia under primitiveconditions differ from those under peaceful circumstances. It is important not to blunt the reflexes that guard vital functions. Safety requirements concerning breathing, circulation, and drug interaction must be sharpened because professional surveillance of the patient may be restricted. The halothane-diethyl-ether azeotrope (HE azeotrope) has properties that could make it suitable for anaesthesia under adverse circumstances. We have re-evaluated the HE azeotrope with special reference to safety in studies on 102 patients and 19 pigs.The vaporizers were calibrated to guarantee their performance. Guidelines for the use of Auotec® Mark Ill and Servo® vaporizer for halothane combined with the HE azeotrope are set out. Minimum alveolar concentration (MAC) for the HE azeotrope has not previously been published. The MAC for the HE azeotrope was determined in man (0.71 vol.%± 0.03, ± SEM) and pig (0.99 vol.%± 0.07) to allow comparison with other inhalation anaesthetics. The safety ratio defined as the ratio between fatal alveolar concentration and minimum alveolar concentration was found to be 3.1 in pig, which is about twice as high as previously reported data for halothane anaesthesia alone.Ventilation during surgical anaesthesia (1.1-1.2 MAC), both when resting and during challenge with raised inspiratory levels of carbon dioxide and decreased inspiratory concentration of oxygen, was measured. Ventilation was maintained during resting. Response to hypercarbia was preserved, in contrast to what was seen under isoflurane anaesthesia. Response to hypoxia was abolished.The central circulation was well preserved under normovolaemia in pigs during HE azeotrope anaesthesia. Haemorrhage. with a loss of30% of the blood volume was well tolerated, no matter whether the pig had received HE azeotrope or isoflurane. Isoflurane is considered in the literature to be an anaesthetic well tolerated by pigs.Most inhalation anaesthetics potentiate neuromuscular blockade, which is an important and sometimes dangerous component of anaesthesia. We therefore thought it important to investigate whether interaction takes place between vecuronium induced neuromuscular blockade and the HE azeotrope. Potentiation similar to that occurring during halothane anaesthesia was found.Early postoperative liver function was studied by tests of cellular metabolic capacity, cell integrity, cholestasis, and synthesizing capacity. No major impact on hepatic function after HE azeotrope anaesthesia was seen.Thus, the halothane-diethyl-ether azeotrope has properties that could make it interesting as an alternative anaesthetic drug under difficult circumstances.

Two groups of paediatric patients, consisting of 40 patients each, were studied with regard to anaesthesia induction and recovery. Group H was given halothane and Group E received enflurane. The induction time was similar for the two groups. Enflurane had, on average, a shorter recovery time (17 +/- 4 min) than halothane (26 +/- 4min) (P less than 0.05). The mean dose of anaesthetic given, expressed as the product of inspired concentration times minute ventilation, was 2.3 +/- 0.2 1 100% halothane and 2.8 +/- 0.2 1 100% enflurane. If one assumes that the minimum alveolar concentration (MAC) value for enflurane twice that of halothane, group E received a less potent anaesthetic dose. This might explain the similar induction times, and, in part, the shorter recovery time for enflurane in this study. No difference was noted between the two agents with regard to post-operative nausea and vomiting or restlessness.