Methoxyflurane revisited: tale of an anesthetic from cradle to grave

Anesthesiology. 2006 Oct;105(4):843-6. doi: 10.1097/00000542-200610000-00031.


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.

Publication types

  • Biography
  • Classical Article
  • Comment
  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anesthesiology / history*
  • Anesthetics, Inhalation / adverse effects
  • Anesthetics, Inhalation / history*
  • Anesthetics, Inhalation / pharmacokinetics
  • Animals
  • Fluorides / metabolism
  • History, 20th Century
  • Humans
  • Kidney Diseases / chemically induced
  • Methoxyflurane / adverse effects
  • Methoxyflurane / history*
  • Methoxyflurane / pharmacokinetics
  • Oxalic Acid / metabolism
  • Rats


  • Anesthetics, Inhalation
  • Methoxyflurane
  • Oxalic Acid
  • Fluorides

Personal name as subject

  • Richard I Mazze