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PubMed2002

Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice.

The effects of gamma-aminobutyric acid (GABA) receptor modulators and GABA uptake inhibitors on volatile and intravenous anesthetic-induced anesthesia were examined in male ICR mice, as assessed by the loss of righting reflex (LORR). The GABA uptake inhibitors, NO-711 and SKF89976A, which are permeable to the blood-brain barrier (BBB), but not nipecotic acid or guvacine, which poorly permeate BBB, shortened the onset of LORR but did not affect the duration of LORR induced by 1.5% halothane and 2% isoflurane. NO-711 and SKF89976A shortened the onset of and prolonged the duration of LORR induced by thiamylal (45 mg/kg i.p.). The GABA mimetics, muscimol and diazepam, shortened the onset of and prolonged the duration of LORR induced by halothane, isoflurane, and thiamylal. On the other hand, picrotoxin, a GABAA receptor antagonist, prolonged the onset of LORR induced by all anesthetics tested. Another GABAA receptor antagonist, bicuculline, prolonged the onset of LORR induced by halothane, but not by isoflurane or thiamylal. Both antagonists failed to affect the duration of LORR induced by halothane, isoflurane, or thiamylal. Baclofen, a GABAB receptor agonist, enhanced both volatile anesthetics- and thiamylal-induced anesthesia. These results suggest that anesthesia induced by volatile and intravenous anesthetics might be correlated with the modification of the pre- and/or postsynaptic GABAergic activities.

Anesthesia↗
PubMed1987

Hepatic glutathione S-transferase release after halothane anaesthesia: open randomised comparison with isoflurane.

Plasma concentrations of hepatic glutathione S-transferase (GST) are a more sensitive measure of acute hepatic damage than aminotransferase activity. Plasma GST concentrations have been measured by radioimmunoassay in an open randomised study after halothane or isoflurane anaesthesia. The concentration of GST was significantly increased after anaesthesia in patients who received halothane in 30% oxygen/70% nitrous oxide (n = 37) and in patients who received halothane in 100% oxygen (n = 17). The frequency of abnormal GST concentrations, defined as 4 micrograms/l or more, was 35% and 24%, respectively. GST concentrations usually reached a peak 3-6 h after the end of anaesthesia. In 17 patients who received isoflurane in 30% oxygen/70% nitrous oxide, there was no significant rise in GST concentration and no patient had a concentration above 4 micrograms/l. No patient in any of the groups had a significant increase in alanine aminotransferase. In clinically identical situations, anaesthesia with halothane but not isoflurane leads to demonstrable impairment of hepatocellular integrity.

Adult↗
PubMed2003

On the use of isoflurane versus halothane in the study of visual response properties of single cells in the primary visual cortex.

Halothane is a widely used anesthetic in research. It produces several alterations in organs, especially in the brain. Recently, isoflurane emerged in neuroscience laboratories. For many reasons it appears to be better than halothane for animal brain research (e.g. isoflurane induces lower intracranial pressure, and is less detrimental on the cardiovascular system). However, no one is in a position to recommend it in electrophysiology research because its effects on specific brain functions are relatively unknown. Given that both anesthetics yield different actions on gross brain activity (EEG, VEP), it is likely that they differentially affect single neuron activity. The goal of this study is to determine whether halothane or isoflurane use is best suited to study the receptive field properties of neurons in the cat's primary visual cortex. Extra-cellular recordings were made for both anesthetics in area 17 of adult cats under different levels of anesthesia. Results indicate that various cell parameters differ under halothane anesthesia when compared with isoflurane. The main difference between the two anesthetics is the greater depression of the cell optimal visual response amplitude induced by isoflurane at equipotent concentration. Due to its stronger depressive effects, isoflurane may not be the ideal anesthetic for single-cell recordings in the primary visual cortex.

Action Potentials↗
PubMed1997

Kupffer cells from halothane-exposed guinea pigs carry trifluoroacetylated protein adducts.

The anesthetic, halothane, is bioactivated by the liver cytochrome P450 system to trifluoroacetyl-chloride, which can readily acylate liver protein. Covalent binding of the trifluoroacetyl moiety may result in hapten formation leading to the induction of an immune response and ultimately halothane hepatitis. In this study the presence of trifluoroacetylated-protein adducts in Kupffer cells was investigated to learn how the immune system might come in contact with the proteins. Guinea pigs were exposed to 1.0% halothane, 40% oxygen for 4 h. Kupffer cells were isolated on days 1 through 9 post-exposure, by liver perfusion and purification by elutriation. Using gel electrophoresis and Western blotting techniques, it has been demonstrated that Kupffer cells obtained from halothane-treated guinea pigs, do carry trifluoroacetyl-protein adducts as recognized by an anti-trifluoroacetyl-rabbit serum albumin antibody. Apparent molecular weights of polypeptides bound by trifluoroacetyl were of a wide range, 25-152 kDa. Bands were most prominent in the larger Kupffer cells with more appearing at lower molecular weights. Trifluoroacetyl-protein adducts were not detected in lung, spleen, lymph node or peripheral blood macrophages. This work suggests a role for Kupffer cells in the presentation of altered proteins in the liver to cells of the immune system.

Acetylation↗
PubMed1998

Changes in the defense against free radicals in the liver and plasma of the dog during hypoxia and/or halothane anaesthesia.

Defenses against free radicals were evaluated in the dog under different conditions of ventilation. Changes in the levels of reduced glutathione (GSH), alpha-tocopherol (vitamin E), ascorbic acid (vitamin C) and the lipid peroxidation end-products, estimated as malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), were studied in serial liver biopsies from dogs ventilated with either oxygen, halothane and oxygen, hypoxic gas mixture of 8% oxygen and 92% nitrogen or halothane under hypoxic conditions. Simultaneous determination of GSH, vitamin E and MDA were carried out in the plasma. The results showed time-dependent depletion of GSH and vitamin E in liver and plasma and vitamin C in the liver. This was accompanied by a simultaneous increase in the levels of MDA. The magnitude of the change was in the following order: halothane and hypoxia > hypoxia > halothane and oxygen > oxygen. The greatest depletion was observed for vitamin E and the least for vitamin C. The rise in the level of MDA in plasma was much higher than in the liver tissue. Hypoxia resulted in inhibition of liver SOD activity. It seems that increased production of free radicals under hypoxic conditions may have overwhelmed the anti-oxidant defenses in the liver. In addition, the much higher level of MDA in plasma, as compared to liver tissue, may indicate that MDA could have originated in tissues or organs other than the liver and leaked into the blood, indicating possible damage in other locations in the body.

Anesthesia↗
PubMed1983

Microvascular response in cancellous bone to halothane-induced hypotension in pigs.

The microvascular response in cancellous bone to halothane-induced hypotension was studied simultaneously using Laser Doppler Flowmetry (LDF) and clearance of locally injected 133Xe in the subapical mandibular bone of 16 young pigs. During halothane inhalation, a significant reduction in mean blood pressure to values ranging from 22 to 60 mm Hg was observed. The blood flow, as measured with LDF, increased in more than 60% of the animals with hypotension levels above 30 mm Hg. At hypotension levels below 30 mm Hg, blood flow decreased in all cases. The individual regional vascular resistance, calculated as the quotient between blood pressure and recorded blood flow value, was significantly reduced (p less than 0.001) during hypotension. Rhythmical flow variations, observed in some animals at normotension, disappeared immediately following the start of halothane inhalation, but returned when blood pressure was stabilized at a lower level. For recordings made with 133Xe-clearance, a significant reduction (p less than 0.001) in the logarithmic decay of the washout curves was observed during hypotension. This logarithmic decay was correlated to the reduced blood pressure levels (r = 0.73). No average change in regional vascular resistance could, however, be demonstrated. The lack of correlation between results obtained by the 2 methods may be due to the fact that LDF is sensitive to the total blood flow in a limited tissue volume, while the 133Xe isotope seems to be washed out mainly by the capillary blood flow. It can be further concluded that halothane-induced hypotension levels, applicable to clinical routines, may produce an increase rather than a decrease in total blood flow in cancellous bone tissue.

Animals↗
PubMed2000

Gamma-aminobutyric acid enhancement of halothane binding in rat cerebellum.

Quantitative autoradiography of 14C-halothane direct photolabeled rat cerebellum sections was performed in the presence of increasing concentrations of gamma-aminobutyric acid (GABA) or glutamate to test the hypothesis that a coupled binding equilibrium between the anesthetic and neurotransmitter exists. The results show that halothane binding was enhanced in the presence of GABA by approximately 50% in the molecular layer and to a lesser extent in the granular layer, with no change in the myelin layer. Glutamate, however, did not enhance halothane binding in any layer. These data confirm the presence of coupling, and thus suggest a direct interaction of halothane with a GABA binding protein.

Animals↗
PubMed2003

Increased sensitivity to halothane but decreased sensitivity to propofol in mice lacking the N-type Ca2+ channel.

Volatile anesthetics are known to depress excitatory synaptic transmission. Inhibition of voltage-dependent Ca2+ channels is speculated to underlie this mechanism, which remains to be clarified in vivo. We examined the sensitivity to halothane in mice lacking the N-type Ca2+ channel, a major contributor of presynaptic neurotransmitter release. Sensitivity to halothane was significantly increased in the knockout mice compared with the wild-type littermates. Halothane also depressed field excitatory postsynaptic potentials recorded from the Schaffer collateral-CA1 hippocampal synapses more greatly in the knockout mice. We further examined sleep time induced by injection of propofol, an intravenous anesthetic that mainly affects inhibitory synaptic transmission. In contrast, sensitivity to propofol was significantly decreased in the knockout mice. We suggest that inhibition of the N-type Ca2+ channel underlies mechanisms of halothane anesthesia but counteracts propofol anesthesia.

Anesthetics, Inhalation↗
PubMed2002

Translocation of protein kinase C by halothane in cholinergic cells.

Protein kinase C (PKC) is a signal transducing enzyme that is an important regulator of multiple physiologic processes and a potential molecular target for volatile anaesthetic actions. However, the effects of these agents on PKC activity are not yet fully understood. Volatile anaesthetics increase intracellular calcium concentration ([Ca(2+)](i)) in a variety of cells, thus their effects on PKC activity may be indirect due to [Ca(2+)](i) increase. Alternatively, the anaesthetics could directly stimulate PKC activity. In order to distinguish these two possibilities in intact cells, we used a fully functional green fluorescent protein conjugated PKCbetaII (GFP-PKCbetaII) and confocal microscopy to evaluate the dynamic redistribution of PKC in living SN56 cells, a cholinergic cell line, in response to halothane. Halothane induced PKC translocation in SN56 cells transfected with GFP-PKCbetaII. This effect was not suppressed by dantrolene, a drug that blocks halothane-induced Ca(2+) release from intracellular stores in these cells. These findings indicate that halothane induces PKC translocation in SN56 cells independently of its ability to release calcium from internal stores.

Anesthetics, Inhalation↗
PubMed1998

Effects of halothane and methoxyflurane on the hypothalamic-pituitary-adrenal axis in rat.

Effects of acute exposure (2 h) to either 1.5% halothane or 0.5% methoxyflurane on chemical mediators of the hypothalamic-pituitary-adrenal (HPA) axis were evaluated in male Sprague-Dawley rats immediately after exposure, after the righting reflex (4 h), or 24 h postexposure. Effects of these anesthetics on hippocampal corticotropin releasing factor (CRF) were also evaluated. Methoxyflurane caused significant elevations in pituitary adrenocorticotropin hormone (ACTH)-like immunoreactivities in all three of the experiment's time groups, yet halothane failed to cause the same response immediately after exposure. Serum ACTH-like immunoreactivities were significantly elevated immediately after exposure to both anesthetics, but were not elevated at 4 and 24 h postexposure. Corticosterone (CORT)-like immunoreactivities were significantly elevated by halothane in all experimental groups, and in the 2- and 24-h groups following methoxyflurane exposure. Hippocampal CRF-like immunoreactivities remained unaffected by either anesthetic. Results indicate that a 2-h exposure to either halothane or methoxyflurane results in significant activation of the rat hypothalamic-pituitary-adrenal axis, and that the activation appears to be sustained over a 24-h period.

Adrenocorticotropic Hormone↗
PubMed1988

[Effects of isoflurane and halothane on the auditory and somatosensory evoked potentials].

The effects of isoflurane and halothane anaesthesia on brainstem auditory (BEAR) and somatosensory evoked potentials (SEP) were recorded in 15 patients; eight received isoflurane and seven halothane. Atropine alone was given as premedication. After induction of anaesthesia with thiopentone, it was maintained with 50% nitrous oxide in oxygen. Ventilation was controlled. Isoflurane and halothane concentrations were gradually increased to 3%. Recordings were made at 1%, 2.5% and 3%. There were statistically significant differences in the latencies of SEP and BEAR with increasing concentrations of anaesthetic. The BEAR waves significantly affected were wave V and the latency between peaks I to V (p less than 0.001); for the SEP, it was wave N20. SEP central conduction time was prolonged with both anaesthetics (p less than 0.001). The effects of isoflurane and halothane were similar. These results could not be explained by changes in central body temperature or end-tidal carbon dioxide concentration. The study showed a dose-related direct effect of both anaesthetic agents on the brainstem auditory and somatosensory evoked responses. It may be that the measurement of changes in evoked potentials could be a useful indicator of anaesthetic depth.

Adult↗
PubMed1989

[Use of halothane in a semi-closed circuit].

Halothane was administered to 10 ASA or 11 patients undergoing elective peripheral surgery. The vaporizer was included in the delivery gas line of the semiclosed system. Löwe's square root of time model of uptake was used to calculate the required doses of halothane. In order to reach an alveolar concentration corresponding to 1.3 MAC, 0.5 vol % of halothane (1.3 MAC) combined with 60 vol % of nitrous oxide (0.6 MAC) were administered at a fresh of 20 ml.kg-1. The ventilation controlled in order to maintain end-tidal CO2 partial pressure at a 5 vol %. Inspiratory halothane concentration was measured during the inspiratory plateau. The alveolar fraction was defined as being the mean end expiratory concentration. The latter was well above the theoretical values during the first 9 min of anaesthesia (0.85% at the 4 th min). This concentration then decreased progressively, becoming less than the expected value after 15 min (0.4% at the 30 th min). Löwe's model would therefore seem to lead to a gross overestimation of the amount of anaesthetic vapour to be delivered to a patient at the beginning of anaesthesia, and an underestimation thereafter.

Anesthesia, Inhalation↗
PubMedDate not supplied

Effects of halothane reexposure in female mice and their offspring.

Female CBi mice subjected to multiple exposures to halothane inhalation anesthesia before mating were investigated for the potential effects of such intervention on a specific antibody response mounted by them and their offspring. An assessment of the toxicologic and reproductive performance of female mice undergoing anesthesia was also performed. Adult female mice received three episodes of halothane anesthesia at weekly intervals. Seventy-two hours after the last dose, mice were subjected to the following procedures: 1) study of the specific humoral immune response to sheep red blood cells (SRBC); 2) hematologic, hepatologic, and histopathologic studies; and 3) mating with syngeneic sires. Halothane-treated females had increased amounts of specific antibody secreting B cells, with liver studies showing evidence of microscopic fatty changes and decreased lipid peroxidation. Anesthesia did not alter reproductive performance but lowered offspring survival. Offspring displayed depressed antibody response after challenge with SRBC at weaning and at 60 d of age. The anti-SRBC antibody response that was found to be enhanced in halothane anesthetized females, seemed to be conversely impaired when studied in the offspring.

Anesthetics, Inhalation↗
PubMed2000

Emergence characteristics of sevoflurane compared to halothane in pediatric patients undergoing bilateral pressure equalization tube insertion.

STUDY OBJECTIVE: To compare the emergence characteristics of sevoflurane with halothane in pediatric patients having bilateral myringotomy and pressure equalization tube insertion using a highly standardized and common anesthetic technique. DESIGN: Prospective, randomized, double-blind study. SETTING: University hospital. PATIENTS: 43 ASA physical status I and II healthy pediatric outpatients scheduled for initial ear tube placement by one surgeon. INTERVENTIONS: Patients were randomized to receive either halothane or sevoflurane as their sole anesthetic drug for ear tube insertion. All patients as well as the research nurse grading emergence agitation were blinded to group assignment. No premedication was administered, and all patients received a standard dose of rectal acetaminophen for postoperative pain control. MEASUREMENT AND MAIN RESULTS: The primary outcome was the percentage of patients with emergence agitation, defined as thrashing behavior requiring physical restraint for greater than three minutes. Time to discharge from the postanesthesia care unit (PACU) and from the hospital were also compared. Sevoflurane patients had a greater incidence of emergence delirium: 57% versus 27% [95% CI (1.7%-58.1%) p = 0.047]. Time to discharge from the PACU and the hospital were longer for patients who received sevoflurane: 62 versus 50 min [95% CI (1.4-23.6) p = 0.02] and 102 versus 79 mins [95% CI (9.6-37.1) p = 0.003]. CONCLUSION: In our institution there is a trend toward greater emergence agitation in ear tube placement patients given sevoflurane versus halothane anesthesia. Further, (with our discharge criteria) patients are actually discharged from the PACU and the hospital faster when given halothane as a sole anesthetic when compared to sevoflurane.

Anesthesia, Inhalation↗
PubMed2001

Postoperative recovery following outpatient pediatric myringotomy: a comparison between sevoflurane and halothane.

STUDY OBJECTIVE: To assess recovery in children undergoing myringotomy and anesthetized using sevoflurane or halothane with special reference to the phenomenon of excitation reported in previous studies. DESIGN: Prospective, randomized, single-blind study. SETTING: Regional (district general) hospital. PATIENTS: 60 healthy, physical status I children (aged 3 to 8 years) presenting for elective outpatient myringotomy. INTERVENTIONS: The children were premedicated with midazolam and paracetamol and randomly allocated to one of two groups: Group H were induced with halothane (0.5% to 5%) and Group S with sevoflurane (1% to 8%). Anesthesia was maintained with oxygen (FIO(2) = 0.33), nitrous oxide, and the study drug. No opioids were administered during surgery. Postoperatively, propofol was given (1 mg/kg) if the child was crying and uncontrollable on the excitation scale for >5 minutes. Total analgesic consumption and side effects were recorded. MEASUREMENTS AND MAIN RESULTS: Postoperatively, the following parameters were recorded: time to eye opening, excitation, pain, time to sit unaided, time to drink water, time to walk, and time to discharge home. No differences were found in the demographic data, duration of anesthesia and operation, time to loss of eyelash reflex, time to waking up, incidence of postoperative excitation (7% and 8% in the sevoflurane and halothane groups respectively), pain, or postoperative nausea and vomiting. The ability to sit and walk, and the time to discharge home (mean 60.4 min vs. 67.1 min, respectively) was similar between the groups. CONCLUSIONS: Although some studies have reported a high incidence of excitation following sevoflurane anaesthesia, we found no differences between halothane and sevoflurane. This finding could be due to the midazolam given as premedication as well as minimal postoperative pain in these children.

Akathisia, Drug-Induced↗
PubMed1995

Comparison of the alteration of cardiac function by sevoflurane, isoflurane, and halothane in the isolated working rat heart.

OBJECTIVES: Despite its widespread use, little is known about sevoflurane's physiologic effects. The direct myocardial effects of sevoflurane were compared with both halothane and isoflurane. DESIGN: Administration of minimum alveolar concentration (MAC) fractions of anesthetic (0 to 3.0) was systematically varied to decrease the possibility of time-related effects on measured parameters. SETTING: Isolated rat hearts were perfused using a working heart model where the parameters affecting myocardial work were carefully controlled and monitored. PARTICIPANTS: To avoid confounding effects of prior anesthetic administration, hearts were removed from rats, after decapitation, in the absence of anesthetic. INTERVENTIONS: In the first series, isolated perfused rat hearts were exposed to one of the three anesthetics in doses of 0 to 1.5 times MAC. In the second series, hearts were exposed to either sevoflurane or isoflurane in doses of 0 to 3.0 times MAC. The following variables were measured: the rate of change of left ventricular pressure; aortic flow rate; cardiac output; left ventricular end-diastolic pressure; the time constant of isovolumetric relaxation; and coronary vascular resistance. Oxygen consumption was measured during the first series. MEASUREMENTS AND MAIN RESULTS: In the first series, all systolic variables were reduced in the presence of halothane when compared with either isoflurane or sevoflurane. Halothane affected diastolic function to a greater degree than either sevoflurane or isoflurane, as measured by the rate of relaxation and end-diastolic pressure. In the second series, at a dose of 3.0 times MAC, both sevoflurane and isoflurane decreased systolic and diastolic function, with a greater reduction in cardiac output, and peak aortic flow and higher left ventricular end-diastolic pressures observed with isoflurane. Coronary resistance and oxygen consumption were not affected by any of the anesthetics. CONCLUSIONS: These data suggest that sevoflurane depresses cardiac function less than either halothane in doses of 1.0 and 1.5 x MAC or isoflurane at doses of 3 x MAC.

Anesthetics, Inhalation↗
PubMed2001

Similar haemodynamic, respiratory and metabolic changes with the use of sevoflurane or halothane in children breathing spontaneously via a laryngeal mask airway.

BACKGROUND: In preschool children, short-lasting surgical procedures are often performed under combined inhalational and regional anaesthesia with the child breathing spontaneously via a laryngeal mask airway (LMA). Despite widespread use, only limited data are available on haemodynamic, respiratory and metabolic effects of sevoflurane and halothane during LMA anaesthesia. METHODS: In an open-label, randomised, controlled study, 49 children (aged 3-8 years) were allocated to receive either sevoflurane or halothane in 60% nitrous oxide. After insertion of the LMA, end-tidal concentrations of sevoflurane or halothane were maintained at 1 MAC with the child ventilating spontaneously throughout the entire procedure. Analgesia was provided by caudal block. Haemodynamic and respiratory parameters were recorded, and capillary blood-gas samples were obtained repeatedly. RESULTS: Changes in heart rate (HR) and systolic blood pressure were similar in both groups during all observed periods, apart from a significantly higher increase in HR during inhalational induction with sevoflurane (P<0.05). Regression slope analysis during anaesthesia revealed a decrease of the respiratory rate of 5 breaths h-1 (P<0.001) and an increase of end-tidal PCO2 and capillary PCO2 of about 0.25 kPa h-1 (P<0.001), with no significant difference between the two groups. Base excess, calculated in capillary blood gas samples, did not change over time (P>0.5) in either group. CONCLUSIONS: The use of approximately 1 MAC sevoflurane or halothane in 60% N2O in children breathing spontaneously via LMA resulted in comparable haemodynamic, respiratory and metabolic changes, and clinically relevant deteriorations did not occur during the 65-min study period.

Anesthesia, Inhalation↗
PubMed2006

Apparent 'electrocatalytic' activity of multiwalled carbon nanotubes in the detection of the anaesthetic halothane: occluded copper nanoparticles.

The electrocatalytic detection of the anaesthetic halothane on a multiwalled carbon nanotube modified glassy carbon electrode is reported with a low limit of detection of 4.6 microM. A thorough investigation of the underlying cause of this apparent catalytic effect is undertaken by comparing the response of various carbon electrodes including glassy carbon, basal- and edge-plane pyrolytic graphite electrodes (bppg and eppg respectively) to increasing additions of halothane. The reduction of halothane is shifted by 250-300 mV to more negative potentials at an eppg electrode than that observed at the GC-CNT electrode. Therefore the results of this investigation show that, surprisingly, the electrocatalysis is not solely due to the introduction of edge-plane-like defect sites on the carbon nanotubes as is commonly found for many other substrates showing favourable voltammetry at nanotube modified electrodes. Instead, we reveal that in this unusual case the electroactive sites for the reduction of halothane are due to the presence of copper nanoparticles occluded within the carbon nanotubes during their production, which are never completely removed by standard purification techniques such as acid washing. This is only the third known case where apparent electrocatalysis by carbon nanotube modified electrodes is due to occluded metal-related nanoparticles within the nanotube structure, rather than the active sites being the edge-plane-like defect sites on the nanotubes. Furthermore this is the first case where the active sites are nanoparticles of copper metal, rather than metal oxide nanoparticles (namely oxides of iron(II)/(III)) as was found to be the case in the previous examples.

Anesthetics↗