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methoxyflurane

methoxyflurane

introduction

  • 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.

pharmacology

  • 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

contraindications

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

adverse effects

irreversible, dose-dependent nephrotoxicity

  • 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.

hepatotoxicity

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

at analgesic 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.

occupational exposure

  • 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

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

administration

'Penthrox' inhaler

  • 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.

references and other resources

  • Review article by Grindlay and Babl. Emergency Medicine Australasia (2009) 21, 4-11.
methoxyflurane.txt · Last modified: 2019/06/27 17:36 (external edit)