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Anesthesiology Oct 2021The Solubility of Halothane in Blood and Tissue Homogenates. By Larson CP, Eger EI, Severinghaus JW. Anesthesiology 1962; 23:349-55. Measured samples of human and bovine...
The Solubility of Halothane in Blood and Tissue Homogenates. By Larson CP, Eger EI, Severinghaus JW. Anesthesiology 1962; 23:349-55. Measured samples of human and bovine blood, human hemoglobin, and tissue homogenates from human fat and both human and bovine liver, kidney, muscle, whole brain, and separated gray and white cortex were added to stoppered 2,000-ml Erlenmeyer flasks. To each flask, 0.1 ml of liquid halothane was added under negative pressure using a calibrated micropipette. After the flask was agitated for 2 to 4 h to achieve equilibrium between the gas and blood or tissue contents, a calibrated infrared halothane analyzer was used to measure the concentration of halothane vapor. Calculated partition coefficients ranged from 0.7 for water to 2.3 for blood and from 3.5 for human or bovine kidney to 6 for human whole brain or liver and 8 for human muscle. Human peritoneal fat had a value of 138. The human blood-gas partition coefficient of 2.3 as determined by this equilibration method was well below the previously published value of 3.6.
Topics: Anesthetics, Inhalation; Animals; Biomedical Research; Cattle; Halothane; Humans; Solubility; Tissue Distribution
PubMed: 34499097
DOI: 10.1097/ALN.0000000000003952 -
Anesthesiology Nov 2020The degree to which different volatile anesthetics depress carotid body hypoxic response relates to their ability to activate TASK potassium channels. Most commonly,...
BACKGROUND
The degree to which different volatile anesthetics depress carotid body hypoxic response relates to their ability to activate TASK potassium channels. Most commonly, volatile anesthetic pairs act additively at their molecular targets. We examined whether this applied to carotid body TASK channels.
METHODS
We studied halothane and isoflurane effects on hypoxia-evoked rise in intracellular calcium (Ca2+i, using the indicator Indo-1) in isolated neonatal rat glomus cells, and TASK single-channel activity (patch clamping) in native glomus cells and HEK293 cell line cells transiently expressing TASK-1.
RESULTS
Halothane (5%) depressed glomus cell Ca2+i hypoxic response (mean ± SD, 94 ± 4% depression; P < 0.001 vs. control). Isoflurane (5%) had a less pronounced effect (53 ± 10% depression; P < 0.001 vs. halothane). A mix of 3% isoflurane/1.5% halothane depressed cell Ca2+i response (51 ± 17% depression) to a lesser degree than 1.5% halothane alone (79 ± 15%; P = 0.001), but similar to 3% isoflurane alone (44 ± 22%; P = 0.224), indicating subadditivity. Halothane and isoflurane increased glomus cell TASK-1/TASK-3 activity, but mixes had a lesser effect than that seen with halothane alone: 4% halothane/4% isoflurane yielded channel open probabilities 127 ± 55% above control, versus 226 ± 12% for 4% halothane alone (P = 0.009). Finally, in HEK293 cell line cells, progressively adding isoflurane (1.5 to 5%) to halothane (2.5%) reduced TASK-1 channel activity from 120 ± 38% above control, to 88 ± 48% (P = 0.034).
CONCLUSIONS
In all three experimental models, the effects of isoflurane and halothane combinations were quantitatively consistent with the modeling of weak and strong agonists competing at a common receptor on the TASK channel.
Topics: Anesthetics, Inhalation; Carotid Body; Cell Hypoxia; Drug Combinations; Drug Interactions; HEK293 Cells; Halothane; Humans; Isoflurane; Nerve Tissue Proteins; Potassium Channels, Tandem Pore Domain
PubMed: 32826405
DOI: 10.1097/ALN.0000000000003520 -
British Medical Journal May 1980
Topics: Anesthesia, General; Chemical and Drug Induced Liver Injury; Enflurane; Enzyme Induction; Halothane; Humans; Liver
PubMed: 7388468
DOI: No ID Found -
Postgraduate Medical Journal Mar 1989
Review
Topics: Adult; Chemical and Drug Induced Liver Injury; Halothane; Humans; Liver Diseases; Male; Middle Aged; Risk Factors
PubMed: 2682584
DOI: 10.1136/pgmj.65.761.129 -
Environmental Health Perspectives Dec 1977Current knowledge of the quantitative aspects of biotransformation of halothane and the fate of its metabolites are reviewed. Absorbed quantities of the inhalation... (Review)
Review
Current knowledge of the quantitative aspects of biotransformation of halothane and the fate of its metabolites are reviewed. Absorbed quantities of the inhalation anesthetic average 12.7 and 18 g during 1 and 2 hr, respectively, of anesthesia. Reported fractions of halothane recovered as urinary metabolites range from 10 to 25%. An analysis of reports of bromide ion accumulation in plasma during and following anesthesia suggests that metabolism of halothane continues for 20-40 hr after exposure and that 22-24% of absorbed halothane is metabolized following 8 hr of anesthesia. Half-times for excretion of trifluoroacetic acid (TFA), a principal urinary metabolite of halothane, tend to confirm that biotransformation proceeds for 2 to 3 days following exposure. Other urinary metabolites which occur in small amounts include a dehydrofluorinated metabolite of halothane conjugated with L-cysteine and N-trifluoroacetyl-n-ethanolamine, both of which are evidence of the occurrence of reactive intermediates during the metabolism of halothane. Support for free radical formation has come from in vivo and in vitro demonstrations of stimulation of lipoperoxidation of polyenoic fatty acids by halothane. Irreversible binding of halothane metabolites to microsomal proteins and phospholipids has been shown to depend on the microsomal P-450 cytochrome system. Irreversible binding is increased by microsomal enzyme induction and by anaerobic conditions. Hypoxia increases irreversible binding to phospholipids, augments the release of inorganic fluoride and is followed by centrilobular hepatic necrosis. It is concluded that one-fourth to one-half of halothane undergoes biotransformation in man. One fraction is excreted as trifluoroacetic acid, chloride and bromide. A second fraction is irreversibly bound to hepatic proteins and lipids. Under anaerobic conditions fluoride is released, binding to phospholipids is increased, and hepatic necrosis may occur.
Topics: Anesthesia, Inhalation; Animals; Biotransformation; Body Fluids; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Feces; Halothane; Humans; Liver; Rats; Sweat
PubMed: 348455
DOI: 10.1289/ehp.7721165 -
Eastern Mediterranean Health Journal =... Feb 2012The anaesthetic agent halothane is still widely used in developing countries including the Islamic Republic of Iran because of its low price. Because of... (Review)
Review
The anaesthetic agent halothane is still widely used in developing countries including the Islamic Republic of Iran because of its low price. Because of halothane-induced hepatitis, a rare complication, it has been replaced by other inhalation anaesthetics in Western countries; it has been suggested by some Iranian professionals that the Islamic Republic of Iran should do the same. We evaluated various dimensions of this replacement through a literature review to assess the incidence of halothane-induced hepatitis and costs of anaesthetics in the country. We also conducted a questionnaire survey of 30 anaesthesiology/gastroenterology experts about their views on the subject. The results indicate that the incidence of halothane hepatitis in the Islamic Republic of Iran is very low and could mostly be avoided by strict adherence to guidelines. Complete withdrawal of halothane in the Islamic Republic of Iran might not be appropriate at present. Comprehensive cost-effectiveness studies are needed before a decision is made on complete replacement of halothane with other anaesthetics.
Topics: Anesthetics, Inhalation; Attitude of Health Personnel; Chemical and Drug Induced Liver Injury; Costs and Cost Analysis; Desflurane; Developing Countries; Halothane; Humans; Iran; Isoflurane; Methyl Ethers; Risk Assessment; Sevoflurane; Surveys and Questionnaires
PubMed: 22571093
DOI: 10.26719/2012.18.2.159 -
British Medical Journal Feb 1977
Topics: Anesthesia; Chemical and Drug Induced Liver Injury; Halothane; Humans
PubMed: 843790
DOI: No ID Found -
IARC Monographs on the Evaluation of... 1999
Topics: Animals; Carcinogenicity Tests; Carcinogens; Halothane; Humans; Mutagenicity Tests; Mutagens; Neoplasms, Experimental; Salmonella typhimurium
PubMed: 10476411
DOI: No ID Found -
Anesthesiology Aug 1981
Topics: Animals; Biotransformation; Chemical and Drug Induced Liver Injury; Halothane; Humans; Pharmacogenetics; Rats
PubMed: 7258720
DOI: 10.1097/00000542-198108000-00001 -
Anesthesiology Mar 1978
Topics: Anesthesia, Inhalation; Animals; Halothane; Humans; Mutation; Neoplasms
PubMed: 626420
DOI: 10.1097/00000542-197803000-00001