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PubMed1980

A comparison of the analgesic effects of methoxyflurane-nitrous oxide and nitrous oxide alone during labour related to the Eysenck personality inventory test.

One hundred and thirty-three paturients who had received either methoxyflurane-nitrous oxide or nitrous oxide analgesia with or without pudendal block, underwent the Eysenck Personality Inventory Test on the second postpartum day and evaluated their memory of the pain (Subjectively Evaluated Pain Suffering Scores) during labor. Parturients who had received methoxyflurance-nitrous oxide analgesia reported significantly lower pain suffering than parturients who had had nitrous oxide analgesia. Subdivision according to Personality Inventory factors showed that at the introvert end of the Extroversion-Introversion scale, methoxyflurance-nitrous oxide analgesia with or without additional pudendal block resulted in significantly lower pain suffering than did not nitrous oxide analgesia. On the other hand, nitrous oxide analgesia without additional pudendal block gave significantly lower pain suffering at the extrovert end of the scale. Among the extroverts there was a tendency, though not statistically significant, towards non-approval of the pudendal block.

Anesthesia, Inhalation↗
PubMed1978

Methoxyflurane anesthesia in mule deer (Odocoileus hemionus) fawns.

Methoxyflurane inhalation was used a total of 58 times to anesthetize 23 hand-reared mule deer (Odocoileus hemionus) fawns ranging from 25 to 85 days of age. Induction, maintenance, and recovery times were recorded for 28 anesthetizations. Induction time was unrelated to age and averaged 3 +/- 1 min (X +/- SD). Recovery time was longest in the youngest fawns and varied with the depth but not with the length of anesthesia. Induction and recovery were smooth, the depth of anesthesia was easily controlled, and analgesia and muscle relaxation was excellent. No adverse effects or complications were encountered.

Anesthesia, Inhalation↗
PubMed1975

The comparative evaluation of methoxyflurane and diethyl ether action upon an active sodium transport across isolated frog skin preparation.

The experiments were performed in vitro using the frog skin preparations and Ussing method. The effect of methoxyflurane was investigated in 18 sections and that of diethyl ether in 16 sections. Both the anaesthetics were found to affect the frog skin preparation in qualitatively similar way. They both demonstrated a two-phase character of action. Decrease in active sodium transport is preceeded by a transient increase in bioelectric indices of the membrane. The effect was reversible after removing of the drugs from the medium. In order to determine the mechanism of action of the two anaesthetics they were given in combination with ADH and insulin. It was found that the mechanism of action of both the drugs is not analogical to any of the hormones examined, at least, as far as the first phase of action is concerned.

Animals↗
PubMed1975

[Sodium and water balance in the dog under halothane and methoxyflurane anesthesia (author's transl)].

In our model of volume expanded dogs with an equilibrium between input and renal output of sodium and water halothane anesthesia (1,5 Vol.-% insp.) was performed. In deepening halothane anesthesia we found a progressive decrease of mean aortic pressure, GFR and renal sodium and water excretion. There was a strong correlation between GFR and sodium excretion. With a high GFR significantly more sodium was excreted under halothane, whilst reduction of GFR led to an overproportional decrease of sodium excretion. Urine osmolality, too, depended on GFR under halothane. The results of methoxyflurane anesthesia were quite similansion. Concentrations of inorganic fluoride in serum and urine, which we measured in these experiments, did not result in visible changes of sodium or water balance, compared with the conscious state.

Animals↗
PubMed1992

Analgesia and behavioral responses of dogs given oxymorphone-acepromazine and meperidine-acepromazine after methoxyflurane and halothane anesthesia.

This study was designed to test analgesia, duration, and cardiovascular changes induced by meperidine (MEP) and oxymorphone (OXY) following methoxyflurane (MOF) and halothane (HAL) anesthesia. Eight healthy dogs were given atropine and acepromazine, and anesthesia was induced with thiamylal and maintained with 1.5 minimal alveolar concentration of MOF or HAL for 1 hour during controlled ventilation. Eight treatments were given with each anesthetic: 3 with MEP (0.5, 1.0, and 2.0 mg/kg, IV), 3 with oxymorphone (OXY; 0.05, 0.1, and 0.2 mg/kg, IV), and 2 placebos with sterile water. Test drugs were given at the end of anesthesia when early signs of recovery were evident. Minimal threshold stimulus/response nociception was assessed by use of an inflatable soft plastic colonic balloon. Blood pressures and pulse rate were measured with a noninvasive monitor. Meperidine and OXY were found to be effective analgesics and could be reversed with naloxone. Intravenous administration of 2.0 mg of MEP/kg provided analgesia for 36 +/- 6 minutes and 39 +/- 15 minutes after MOF and HAL, respectively. In contrast, OXY was effective at all 3 doses with effects of IV administration of 0.2 mg of OXY/kg lasting 154 +/- 13 minutes and 152 +/- 12 minutes, after MOF and HAL, respectively. Analgesia could not be demonstrated after anesthesia for acepromazine, MOF, or HAL. Blood pressure was not changed by either anesthetic nor was it influenced by MEP or OXY. Pulse rate was significantly depressed by the higher doses of OXY following HAL, but was not changed by MEP following either anesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Acepromazine↗
PubMedDate not supplied

Long duration local anesthesia with lecithin-coated microdroplets of methoxyflurane: studies with rat skin.

Lecithin-coated microdroplets of methoxyflurane (MOF) are shown to produce local anesthesia of three- to six-day duration in the skin with a single intradermal injection in rats. Anesthesia was quantitated by elevation of the threshold (milliampere) for shock vocalization with intradermal electrodes. Intradermal injection of 0.1 ml 0.5% MOF gave moderate (2.1 mA) anesthesia of approximately three-day duration for a 10-12-mm diameter area, with no damage to the tissue. Higher concentrations gave six-day duration anesthesia at very high level (7 to 12 mA) anesthesia of three- to five-day duration with some damage to the tissue. At 4.4% MOF, ulcers formed in the center of the injection site with maximal dimensions of 1.3 mm (11-13% of the site diameter). Phenol, a widely used neurolytic agent, was tested as a control in the same concentration range. Phenol at 4.4% gave very high level (8 mA) anesthesia for longer than seven-day duration and caused formation of ulcers with maximal dimensions of 3.8 mm (31-38% of the site diameter). Analysis showed that MOF produced less damage than phenol for any given degree of anesthesia. Systemic toxicity and pharmacokinetic data are also presented. Phenol produced a hypothermic reaction and behavioral changes, whereas MOF was without systemic effect. The plasma concentrations of phenol were four to five times greater than those of MOF. These results suggest that MOF may have clinical advantages over phenol.

Anesthesia, Local↗
PubMedDate not supplied

Long duration local anesthesia with lecithin-coated microdroplets of methoxyflurane: studies with human skin.

Lecithin-coated microdroplets of methoxyflurane (MOF) have been reported to produce local anesthesia of long duration in rats. The present study was conducted in two phases. The first phase was open label studies in two human volunteers aimed at determining the effective concentration of MOF in human skin. Over the concentration range of 0.3-2.4%, MOF produced local anesthesia to pinprick and cold stimuli within 15 seconds. The duration of the anesthesia effect of 2.4% MOF in the skin of the buttock, forearm and leg was five to eight days. Microdroplets containing isoflurane, a more volatile agent, gave an anesthetic effect that reversed within two to five hours. In the second phase of the study, the safety and efficacy of MOF were compared to phenol in placebo-controlled and blinded studies using indwelling stimulating electrodes. Phenol was destructive to skin at a concentration necessary to obtain a degree of local anesthesia comparable to MOF. The greater part of the anesthetic effect produced by phenol at this "toxic" concentration was transient (approximately one hour). In contrast to phenol, MOF produced an anesthetic effect lasting four to seven days without producing visible damage to skin. These results suggest that MOF is safer and more efficacious than phenol for producing long-lasting local anesthesia of human skin.

Anesthesia, Local↗
PubMed1990

Perdeuteration of methoxyflurane reduces production of fluorometabolites in mice.

The fluorometabolites of perdeuterated methoxyflurane (D-MOF) compared to the nondeuterated form (H-MOF) were studied in mice. Inorganic fluoride (F) and an organic acid labile fluorometabolite (OALF) were determined at various post-administration times. At 100 minutes after D-MOF, F was decreased 32-38% and OALF was down to 33-45%. After 300 minutes F was 56% less and OALF was 46% less after D-MOF administration. OALF increased 35-38% when H-MOF and D-MOF were diluted in oil compared to the undiluted forms. At three times (10, 30, and 100 minutes) D-MOF resulted in reductions of F to 31-38% of values produced by H-MOF. Also, OALF was reduced to 38-46% with D-MOF compared to H-MOF. These studies suggest that the use of D-MOF in mice results in a significant decrease in the appearance of the fluorometabolites F and OALF. The accumulation of metabolites is thought to be responsible for nephrotoxicity of MOF; therefore, D-MOF should be a much safer agent for use in general anesthesia.

Animals↗
PubMedDate not supplied

Purification and identification of rat hepatic cytosolic enzymes responsible for defluorination of methoxyflurane and fluoroacetate.

Enzymes responsible for the defluorination of methoxyflurane (MOF) and fluoroacetate (FAc) were separated and purified from rat liver cytosol. Both hepatic cytosolic enzymes with defluorination activity were labile and addition of 2-mercaptoethanol had little effect on the stability of these enzymes. Glutathione S-transferase (GT) activity of the same cytosolic fractions was stable for at least 11 days. Separation of defluorination and GT enzymatic activities on DEAE-Sephadex A-50 and reduced glutathione-affinity columns revealed that the defluorinations of MOF and FAc were primarily catalyzed by anionic proteins which also exhibited GT activity. Further identification by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed protein bands with pl values of approximately 6.5 and 6.9 and molecular weights of approximately 20,000. However, other proteins that exhibited no GT activity also defluorinated MOF and FAc, but accounted for only 10% of the total defluorination activity present in anionic proteins. Results from a separate purification experiment using a CM-cellulose column also indicated that the enzymes responsible for defluorination coeluted with cationic GTs. Collectively, these cationic enzymes were responsible for about 20% of the recovered cytosolic defluorination activities. The results suggest that the cytosolic defluorinations of both MOF and FAc are primarily the result of a dehalogenation reaction catalyzed by one or more species of rat liver cytosolic GTs.

Animals↗
PubMed1976

[Inhalation analgesia with methoxyfluran (penthrane) in obstetrics (author's transl)].

In 105 normal spontaneous deliveries the effect of inhalation analgesia with Methoxyfluran (Penthrane) was studied. Penthrane was administered intermittently with the Penthrane oxilator (Rod inhalator of Abbott). The initial concentration was 0.25 volume%. The maximal concentration was 0.35 volume% of Penthrane. Fetal monitoring records were obtained in all deliveries. In 49 cases (46.7%) intra- and post-partum microblood studies were obtained. In 85 women (81.0%) the result of the analgesia was good. Nausea occurred in 21 women (20%). There were no abnormal fetal monitoring patterns. The Apgar scores of the newborns were between 8 and 10. The actual pH's were between 7.24 and 7.41. The third stage of labour was normal in all cases.

Analgesia↗
PubMed1986

Pharmacokinetics of inhaled anesthetics in humans: measurements during and after the simultaneous administration of enflurane, halothane, isoflurane, methoxyflurane, and nitrous oxide.

To determine the relative washin and washout characteristics of isoflurane, enflurane, halothane, and methoxyflurane, we administered all four anesthetics simultaneously (total = 1.1 MAC) to nine healthy patients for 2 hr. Concentrations of anesthetics in end-tidal gases were measured during washin and for 5-9 days during washout. Multiexponential (multicompartment) models were fit to the washin and washout curves using least-squares analysis. Slowly equilibrating compartments could only be identified during washout. For 27 of the 36 data sets, five-compartment models fit the washout curves significantly better than four-compartment models. The time constant for our first compartment is consistent with that predicted for washout of the lungs. Time constants for the second, third, and fifth compartments were consistent with current data for blood flows and solubilities of vessel-rich, muscle, and fat tissue groups, respectively. The fourth compartment has a time constant that lies between the time constants predicted for muscle and fat.

Adult↗
PubMedDate not supplied

A test of the carcinogenicity of enflurane, isoflurane, halothane, methoxyflurane, and nitrous oxide in mice.

We exposed Swiss ICR mice for 2-hour periods to 1/32, 1/8 and/or 1/2 MAC enflurane, halothane, isoflurane, methoxyflurane, or N2O both in utero during the last 1/2 of pregnancy (4 exposures at 2-day intervals) and after delivery (24 exposures at 2-to-3-day intervals). Anesthetics were delivered in air or in O2. Thus, 1973 mice were exposed and examined after 15 months of life for the development of neoplastic lesions. Neoplastic lesions (principally pulmonary adenomas, lymphomas, hepatocyte lesions, liver vascular lesions) were found in all treatment and control sets. There was no indication that a specific anesthetic or anesthetic dose was carcinogenic. Our results do not confirm the suggestion that isoflurane is a hepatocarcinogen, nor do our data suggest that the modern inhaled anesthetics pose a significant threat of carcinogenicity.

Anesthesia, Inhalation↗
PubMed1978

The effect of thiopental sodium, methoxyflurane and halothane on the acid-base status in sheep.

Experiments have been carried out on 20 adult fat-tailed ewes to determine the effects of thiopental sodium, methoxyflurane and halothane on acid-base status of the saliva loss during prolonged surgical anaesthesia. The rate of loss of base in saliva depends on the volume of saliva produced, which fell sharply at the onset of anesthesia with the volatile anaesthesia. Plasma pH and plasma pvCO2 excess were both increased by the volatile anaesthetics but fell sharply during thiopental anaesthesia. Plasma pH and plasma PvCO2 showed no consistent relationship.

Acid-Base Equilibrium↗
PubMedDate not supplied

Hepatitis and renal tubular acidosis after anesthesia with methoxyflurane.

A 69-year-old man operated for acute cholecystitis under methoxyflurane anesthesia developed postoperatively a hepatic insufficiency syndrome and renal tubular acidosis. Massive bleeding appeared during surgery which lasted for six hours. Postoperative evolution under supportive therapy was favourable. Complete recovery was confirmed by repeated controls performed over a period of one year after surgery.

Acidosis, Renal Tubular↗
PubMed1982

Concentrations of methoxyflurane and nitrous oxide in veterinary operating rooms.

The surgical rooms of 14 private veterinary practices were monitored to determined methoxyflurane (MOF) concentrations during surgical procedure under routine working conditions. The average room volume for these 14 rooms was 29 m3. The average MOF value for all rooms was 2.3 ppm, with a range of 0.7 to 7.4 ppm. Four of the 14 rooms exceeded the maximum recommended concentration of 2 ppm. Six rooms which had 6 or more air changes/hr averaged 1.1 ppm, whereas 8 rooms with less than 6 measurable air changes/hr averaged 3.2 ppm. Operating rooms that had oxygen flows of more than 1,000 cm3/min averaged 4.4 ppm, whereas those with flows of less than 1,000 cm3/min averaged 1.5 ppm. The average time spent during a surgical procedure using MOF, for all 14 facilities, was 2 hours. Nitrous oxide (N2O) concentrations were determined in 4 veterinary surgical rooms. The average N2O concentration for 3 rooms without waste anesthetic gas scavenging was 138 ppm. Concentration of N2O in the waste anesthetic gas-scavenged surgical room was 14 ppm, which was below the maximum recommended concentration of 25 ppm.

Air Pollution↗
PubMed1982

Defluorination of methoxyflurane by glutathione and coenzyme B12.

Fluoride was eliminated from methoxyflurane in solutions which contained glutathione and coenzyme B12. The reaction rate was maximal at pH 10 and was dependent upon the concentration of each reactant under specified conditions. A stoichiometric ratio of 2 was found between the amount of glutathione utilized and the amount of fluoride generated in the reaction. Glutathione disulfide was the only stable ninhydrin-positive reaction product identified.

Cobamides↗