Determination of equi-analgesic doses of inhaled methoxyflurane versus intravenous fentanyl using the cold pressor test in volunteers: a randomised, double-blinded, placebo-controlled crossover study

Br J Anaesth. 2021 May;126(5):1038-1045. doi: 10.1016/j.bja.2020.12.045. Epub 2021 Mar 4.

Abstract

Background: Inhaled methoxyflurane for acute pain relief has demonstrated an analgesic effect superior to placebo. Data comparing methoxyflurane to an opioid are needed. The aim of this study was to determine the equi-analgesic doses of inhaled methoxyflurane vs i.v. fentanyl. Both drugs have an onset within minutes and an analgesic effect of 20-30 min.

Methods: Twelve subjects were included in a randomised, double-blinded, placebo-controlled crossover study with four treatments: placebo (NaCl 0.9%), fentanyl 25 μg i.v., fentanyl 50 μg i.v., or inhaled methoxyflurane 3 ml. The subjects reported pain intensity using the verbal numeric rating scale (VNRS) from 0 to 10 during the cold pressor test (CPT). The CPT was performed before (CPT 1), 5 min (CPT 2), and 20 min (CPT 3) after drug administration.

Results: Inhaled methoxyflurane and fentanyl 25 μg reduced VNRS scores significantly compared with placebo at CPT 2 (-1.14 [estimated difference in VNRS between treatment groups with 95% confidence interval {CI}: -1.50 to -0.78]; -1.15 [95% CI: -1.51 to -0.79]; both P<0.001) and CPT 3 (-0.60 [95% CI: -0.96 to -0.24]; -0.84 [95% CI: -1.20 to -0.47]; both P<0.001). There were no significant differences between the two drugs. Methoxyflurane had significantly higher VNRS scores than fentanyl 50 μg at CPT 2 (0.90 [95% CI: 0.54-1.26]; P<0.001) and CPT 3 (0.57 [95% CI: 0.21-0.94]; P<0.001).

Conclusions: Inhaled methoxyflurane 3 ml was equi-analgesic to fentanyl 25 μg i.v. at CPT 2. Both resulted in significantly less pain than placebo. Fentanyl 50 μg i.v. demonstrated analgesia superior to methoxyflurane.

Clinical trial registration: NCT03894800.

Keywords: acute pain; analgesia; cold pressor test; fentanyl; methoxyflurane.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Administration, Intravenous
  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Anesthetics, Inhalation / administration & dosage
  • Anesthetics, Inhalation / pharmacology*
  • Cold Temperature
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fentanyl / administration & dosage
  • Fentanyl / pharmacology*
  • Humans
  • Male
  • Methoxyflurane / administration & dosage
  • Methoxyflurane / pharmacology*
  • Middle Aged
  • Pain / drug therapy
  • Pain Measurement
  • Young Adult

Substances

  • Analgesics, Opioid
  • Anesthetics, Inhalation
  • Methoxyflurane
  • Fentanyl

Associated data

  • ClinicalTrials.gov/NCT03894800