Metabolism of synthane: comparison with in vivo and in vitro defluorination of other halogenated hydrocarbon anaesthetics.

Aerobic defluorination of the inhalation anaesthetic agent, synthane, was compared with that of methoxyflurane, enflurane and halothane and with two other anaesthetics, isoflurane and sevoflurane. In vitro, in microsomes prepared from phenobarbitone-induced and control livers, synthane and halothane were not defluorinated. The relative order of defluorination of the other anaesthetics was methoxyflurane greater than enflurane greater than isoflurane. In vivo, following 4 h of 1.2% (MAC) synthane anaesthesia, urinary inorganic fluoride excretion was increased by only a trivial amount and only in phenobarbitone-treated rats; polyuria was not observed. Synthane is the least metabolized of the fluorinated ether anaesthetics; its administration will not result in inorganic fluoride nephropathy. An index of nephrotoxic potential for fluorinated anaesthetic agents was formulated utilizing in vitro fluoride production data and oil: gas partition coefficients.

Thermoregulatory defect in rats during anesthesia.

Male rats of the Fischer 344, Sprague-Dawley, Brattleboro, and Wistar strains, balb/C mice, and Hartley guinea pigs were divided into 2 treatment groups. One group drank tap water while the other group drank water containing 1 mg/ml of phenobarbital. Animals were exposed to sevoflurane, enflurane, methoxyflurane, isoflurane, or halothane in a closed chamber. In some of the experiments, soda lime was included and in other the chamber was heated to 39 degrees C with a water blanket. Eighty-six percent (43/50) of Fischer 344 rats treated with phenobarbital and esposed to either sevoflurane or enflurane, in the presence of either soda lime or exogenous heat, died within a few hours after exposure. Fischer 344 rats and rats of other strains drinking phenobarbital water and exposed to methoxyflurane were affected, but to a lesser degree. Rats drinking ordinary tap water and phenobarbital-treated rats not exposed to either soda lime or exogenous heat were unaffected. Guinea pigs and mice also were unaffected. We postulate that the toxic response represents a species-specific thermoregulatory defect, precipitated by heat and occurring in rats treated with phenobarbital in combination with sevoflurane, endlurane, or methoxyflurane.

A comparison of renal effects and metabolism of sevoflurane and methoxyflurane in enzyme-induced rats.

Twenty-five 5-month-old male Fischer-344 rats were randomly divided into 5 groups: Group I, no anesthesia; Group II, 1.4 precent sevoflurane for 2 hours; Group III, 0.1 percent phenobarbital, ad lib, in drinking water for 7 days; followed by 1.4 percent sevoflurane for 2 hours; Group IV, 0.25 percent methoxyflurane, 1 hour; Group V, phenobarbital in water as in Group III, followed by methoxyflurane as in group IV. Pre- and postanesthetic serum and urinary osmolality, Na+, K+, urea nitrogen (BUN), inorganic fluoride (F-) levels, and 24-hour urine volume were measured. Kidney tissue was obtained for examination by light and electron microscopy. Sevoflurane was metabolized to F- to a lesser extent than was methoxyflurane; treatment with phenobarbital-sevoflurane doubled urinary F- excretion, resulting in a value similar to that seen after methoxyflurane alone. There was no functional or morphologic evidence of renal abnormalities in either group of rats anesthetized with sevoflurane. Methoxyflurane dosage was sufficiently low that renal abnormalities did not occur except in rats treated also with phenobarbital; these animals developed polyuria and the morphologic lesion typically associated with F--induced nephrotoxicity.

[Renal effects and metabolism of sevoflurane in Fisher 3444 rats: an in-vivo and in-vitro comparison with methoxyflurane].

Sevoflurane, 1.4 per cent (MAC), was administered to groups of Fischer 344 rats for 10 hours, 4 hours, or 1 hour; additional rats received 0.5 per cent methoxyflurane for 3 hours or 1 hour. Urinary inorganic fluoride excretion of sevoflurane in vivo was a third to a fourth that of methoxyflurane. However, using hepatic microsomes, sevoflurane and methoxyflurane were defluorinated in vitro at essentially the same rate. The discrepancy between defluorination of sevoflurane and methoxyflurane in vivo and in vitro was probably due to differences in tissue solubility between the drugs. There were no renal functional or morphologic defects following sevoflurane administration. An unexplained adverse effect was significant weight loss, which occurred following all exposures to sevoflurane.