Analgesic use of inhaled methoxyflurane: Evaluation of its potential nephrotoxicity

Area of Science:

• Anesthesiology
• Nephrology
• Pharmacology

Background:

• Methoxyflurane was previously used for anesthesia at high doses, leading to dose-related renal tubular damage.
• This damage was linked to methoxyflurane metabolism and fluoride ion release.
• Current use involves low-dose, self-administered methoxyflurane for analgesia via the Penthrox inhaler.

Purpose of the Study:

• To discuss the pathogenesis of methoxyflurane-induced renal damage.
• To evaluate the safety of low-dose methoxyflurane for analgesic purposes.
• To provide evidence that current analgesic doses are not associated with renal adverse effects.

Main Methods:

• Review of historical data on high-dose methoxyflurane anesthesia and renal toxicity.
• Analysis of pharmacokinetic and pharmacodynamic data for low-dose methoxyflurane (Penthrox inhaler).
• Examination of clinical experience and laboratory investigations regarding analgesic methoxyflurane use.

Main Results:

• High-dose methoxyflurane anesthesia is associated with nephrotoxicity due to fluoride ion release.
• Analgesic doses are limited to 6 mL/day and 15 mL/week, with a minimum alveolar concentration (MAC) of 0.59 MAC-hours.
• Exposure below 2.0 MAC-hours, resulting in serum fluoride ≤40 µmol/L, shows no renal tubular toxicity.

Conclusions:

• The analgesic use of methoxyflurane in the Penthrox inhaler has a safety margin of at least 2.7- to 8-fold.
• Clinical experience and investigations indicate no risk of nephrotoxicity with subanesthetic doses.
• Methoxyflurane in low analgesic doses is safe for short-term pain management.