see also:

• anaesthetics
• pain, analgesia and analgesics
• Western Health guideline on use of methoxyflurane (pdf) - only available in intranet

• methoxyflurane (“Penthrane”) is a volatile fluorinated hydrocarbon inhaled analgesic and anaesthetic agent.
• it's use as an anaesthetic was ceased in the late 1970's as at anaesthetic concentrations it was found to cause hepatotoxicity and irreversible, dose-dependent nephrotoxicity.
• the US FDA removed it from the register of drugs because of safety concerns, but it is still used in Australia and NZ as an analgesic for pre-hospital and emergency care as “Penthrox” inhaler and “Analgizer” inhaler.
• it's use below is as an analgesic inhaler device, NOT as an anaesthetic.

• not flammable at room temperatures
• colorless liquid with fruity odour
• high blood gas partition coefficient of 13
• potent anaesthetic with MAC of 0.2
• unlike most other anaesthetic agents, it posseses powerful analgesic properties
• 50-70% of absorbed dose undergoes hepatic metabolism via cytochrome P450
  • it is thought that its metabolites (eg. possibly dichloroacetic acid) rather than flouride ions are the cause of the nephrotoxicity

• renal impairment
• diabetes
• concurrent enzyme-inducing drugs or tetracycline
• PH liver damage due to anaesthesia
• PH malignant hyperthermia
• PH hypersensitivity to flourinated anaesthetic agents

• subclinical nephrotoxicity has been calculated to occur at doses of 20-24g in adults
• 6ml (the max. recommended daily dose) delivers < 1.5g methoxyflurane
• 2 fatal cases occurred with doses of 60ml over 14 and 16 days.
• no reported cases at doses of 3ml repeated once with a maximum of 15ml/week.

• rare, and appears to be mainly only associated with repeated anaesthetic doses

• no serious side effects reported when used as sole agent at recommended doses
• minor side effects:
  • drowsiness (27% of children, 11% of adults), restless (17% patients), sedation, hallucinations, vomiting, confusion, dizziness, cough & headache
• possible teratogenicity although seems unlikely.

• unlikely to be a problem unless cumulative exposure in confined spaces (especially if supplemental oxygen used)
• a nurse has developed myasthenic symptoms of ptosis and weakness following prolonged performance of methoxyflurane anaesthesia, but she had subclinical myasthenia gravis which was exacerbated by the methoxyflurane.
• NSW ambulance recommends no more than two patients to be given methoxyflurane per shift and not to use oxygen concurrently.
• Victorian ambulance do allow use of oxygen.

• misuse resulting in repeated exposures may cause:
  • nephrotoxicity
  • hepatotoxicity
  • crystalline retinopathy
  • periosteal new bone formation
  • osteosclerosis
  • psychological dependence

• green plastic tube with a unidirectional valve supplied with 3ml ampoules of methoxyflurane
• the fluid is poured into the non-mouthpiece end whilst holding it upright and the polypropylene wick inside the device then becomes saturated.
• the device has an oxygen port in case supplemental oxygen is needed (but is rarely used and may pose an increased occupational hazard when used in confined spaces)
• the patient then holds the device and breathes through the mouth piece, and alternatively can block the dilutor hole with a finger to increase the inhaled concentration from 0.2-0.4% to 0.5-0.7% (although this may be more than actually delivered as max. concentration is said to be 0.3-0.4% according to manufacturer).
• the dose lasts ~30 minutes and a 2nd and final dose of 3ml can be given if needed.
• a weekly dose of 15ml should not be exceeded, otherwise there is risk of cumulative dose-related nephrotoxicity.

• Review article by Grindlay and Babl. Emergency Medicine Australasia (2009) 21, 4-11.