The Reincarnation of Methoxyflurane.

Methoxyflurane was an inhaled agent commonly used for general anesthesia in the 1960s, but its clinical role gradually decreased in the 1970s because of reports of dose-dependent nephrotoxicity. In 1999 its manufacturer, Abbott Laboratories, discontinued distribution of methoxyflurane in the United States and Canada. Outside of North America, however, methoxyflurane has been reborn as an inhaled analgesic used for pain relief in the prehospital setting and for minor surgical procedures. First used in Australia and New Zealand, and subsequently in over thirty-seven other countries, low concentrations of methoxyflurane are administered with a hand-held inhaler which provides conscious sedation, so that patients can self-assess their level of pain and control the amount of inhaled agent. The Penthrox inhaler, originally developed in Australia after several other hand-held vaporizers were tried, is currently being used worldwide as a portable and disposable self-administered agent delivery system. Methoxyflurane-induced nephrotoxicity continues to be a major concern, but with cautious administration of recommended doses methoxyflurane has been established as a remarkably safe analgesic agent with minimal side effects for patients in need of rapid and potent pain relief.

Methoxyflurane revisited: tale of an anesthetic from cradle to grave.

Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971; 35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and urinary inorganic fluoride excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane induced renal dysfunction. Five patients with clinically evident renal dysfunction had a mean peak serum inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (106 +/- 17 microm). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction.