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

@article{Mazze2006MethoxyfluraneRT,
  title={Methoxyflurane revisited: tale of an anesthetic from cradle to grave.},
  author={Richard I. Mazze},
  journal={Anesthesiology},
  year={2006},
  volume={105 4},
  pages={
          843-6
        }
}
  • R. Mazze
  • Published 1 October 2006
  • Medicine, Biology
  • Anesthesiology
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… 

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References

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Methoxyflurane Metabolism and Renal Dysfunction: Clinical Correlation in Man

TLDR
Evidence is presented to suggest that inorganic fluoride is the substance responsible for methoxyflurane; induced renal dysfunction, and a proposed metabolic pathway to support this hypothesis is presented.

Methoxyflurane nephrotoxicity. A study of dose response in man.

TLDR
The use of methoxyflurane in clinical anesthesia should be restricted to situations where it offers specific advantages and where dosages less than 2.5 MAC hours can be attained.

Nephrotoxicity Associated with Methoxyflurane Anesthesia

TLDR
Among 94 cases in which methoxyflurane was used, 16 developed a toxic nephropathy characterized by diuresis, but in most cases renal functional impairment was transient (10–20 days), but in 3 cases an elevated blood urea nitrogen remained 12, 16 and 29 months after onset.

The etiology of methoxyflurane nephrotoxicity.

TLDR
Inorganic fluoride is responsible for the acute polyuric renal lesion which occurs after methoxyflurane administration, and Pretreatment with SKF 525-A decreased the metabolism of methoxyFLurane and ameliorated its nephrotoxicity.

Metabolism and Renal Effects of Enflurane in Man

TLDR
Metabolism of enflurane to inorganic fluoride was insufficient to cause clinically significant renal dysfunction and postanesthetic renal function was normal in both groups of surgical patients without renal disease.

RENAL DYSFUNCTION ASSOCIATED WITH METHOXYFLURANE ANESTHESIA, A RANDOMIZED, PROSPECTIVE CLINICAL EVALUATION

TLDR
A syndrome was observed, characterized by polyuria, lack of responsiveness to infusion of vasopressin injection, marked weight loss, and delayed return to preoperative renal concentrating ability, indicating a lesion of the distal nephron.

Dose-related Methoxyflurane Nephrotoxicity in Rats: A Biochemical and Pathologic Correlation

TLDR
It was concluded that methoxyflurane produced dose-related nephrotoxicity due to increased concentrations of its metabolite, inorganic fluoride.

Strain differences in metabolism and susceptibility to the nephrotoxic effects of methoxyflurane in rats.

TLDR
A high rate of methoxyflurane metabolism and increased susceptibility to the nephrotoxic effects of inorganic fluoride result in polyuric renal insufficiency in Fischer 344 rats.

A Comparison of the Renal Effects of Isoflurane and Methoxyflurane in Fischer 344 Rats

TLDR
In this animal model, an isoflurane exposure ten times greater than a nephrotoxic exposure to methoxyflurane did not result in sufficient metabolism to inorganic fluoride to cause neph rotoxicity.

Renal Effects and Metabolism of Isoflurane in Man

TLDR
Intra-anesthetic depressions of renal blood flow, glomerular filtration rate and urinary flow rate during isoflurane anesthesia were similar to those seen with halothane, andabolism of is of insufficient magnitude to cause renal dysfunction.