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

  title={Methoxyflurane revisited: tale of an anesthetic from cradle to grave.},
  author={Richard I. Mazze},
  volume={105 4},
  • 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… 

The Reincarnation of Methoxyflurane.

  • S. Ikeda
  • Medicine
    Journal of anesthesia history
  • 2020

Methoxyflurane toxicity: historical determination and lessons for modern patient and occupational exposure.

There are a number of pathways whereby repeated exposure to methoxyflurane in lower doses may pose a risk, and the safety of recurrent patient or occupational healthcare-worker exposure has not been confirmed, and merits further investigation.

S10. Methoxyflurane: Like a Phoenix Rising From the Ashes.

  • L. Dangler
  • Medicine
    Journal of anesthesia history
  • 2015

Case report: proximal tubule impairment following volatile anesthetic exposure

It is suggested that transient proximal tubule impairment may play a role in the proteinuria and glycosuria described following volatile anesthetic exposure and the relationship between these observations and the ability of these agents to protect against ischemic nephropathy.

Analgesic use of inhaled methoxyflurane

  • A. Dayan
  • Medicine
    Human & experimental toxicology
  • 2016
It is concluded from clinical experience in emergency medicine, surgical procedures and various experimental and laboratory investigations that the analgesic use of methoxyflurane in subanaesthetic doses in the Penthrox inhaler does not carry a risk of nephrotoxicity.

Use of Potent Inhalational Anesthetic Agents During Mechanical Ventilation

Halothane, a halogenated alkane, was introduced into clinical practice in 1956 and offered several favorable properties including nonflammability, a favorable blood-gas partition coefficient, and a favorable profile for inhalation induction including a rapid onset and limited pungency, bronchodilatation, relative cardiovascular stability, andA decreased incidence of nausea and vomiting.

Exposure to methoxyflurane: Low-dose analgesia and occupational exposure

The literature is reviewed to identify the relevance of methoxyflurane as an effective analgesic agent, identify whether there are any patient safety concerns in modern use, and determine occupational risk to healthcare personnel due to environmental methoxyFLurane exposure.

Methoxyflurane: A Review in Trauma Pain

Inhaled methoxyflurane may offer advantages over other analgesics administered via the intravenous, intramuscular or intranasal routes in terms of its non-invasive self-administration, ease of use and/or rapid onset of action.

Inhaled methoxyflurane (Penthrox) for analgesia in trauma: a systematic review protocol

This systematic review and meta-analysis will summarise the best available evidence and definitively establish if inhaled methoxyflurane is a superior analgesia to standard care in the acute trauma setting and may require amendments to European pain relief guidelines.



Methoxyflurane Metabolism and Renal Dysfunction: Clinical Correlation in Man

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.

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

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.

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

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.


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

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.

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

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

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.