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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

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 ons...

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Autores principales: Lenz, Harald, Høiseth, Lars Ø., Comelon, Marlin, Draegni, Tomas, Rosseland, Leiv A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132882/
https://www.ncbi.nlm.nih.gov/pubmed/33676727
http://dx.doi.org/10.1016/j.bja.2020.12.045
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author Lenz, Harald
Høiseth, Lars Ø.
Comelon, Marlin
Draegni, Tomas
Rosseland, Leiv A.
author_facet Lenz, Harald
Høiseth, Lars Ø.
Comelon, Marlin
Draegni, Tomas
Rosseland, Leiv A.
author_sort Lenz, Harald
collection PubMed
description 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
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spelling pubmed-81328822021-05-21 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 Lenz, Harald Høiseth, Lars Ø. Comelon, Marlin Draegni, Tomas Rosseland, Leiv A. Br J Anaesth Clinical Investigation 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 Elsevier 2021-05 2021-03-04 /pmc/articles/PMC8132882/ /pubmed/33676727 http://dx.doi.org/10.1016/j.bja.2020.12.045 Text en © 2021 Oslo University Hospital https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Clinical Investigation
Lenz, Harald
Høiseth, Lars Ø.
Comelon, Marlin
Draegni, Tomas
Rosseland, Leiv A.
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Clinical Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132882/
https://www.ncbi.nlm.nih.gov/pubmed/33676727
http://dx.doi.org/10.1016/j.bja.2020.12.045
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