Is Methoxyflurane (penthrox) superior to Entonox

Date First Published:

July 24, 2024

Last Updated:

July 25, 2024

Report by:

Paul Jarvis, Paramedic (Manchester Metropolitan University (MSc Emergency Medicine))

Three-Part Question:

In [adult trauma patients] Is [methoxyflurane Penthrox more effective than Entonox] At [reducing pain]

Clinical Scenario:

While working pre-hospital, you attend an adult patient with severe burns. You have treated the patients pain with IV morphine, IV paracetamol and Entonox. At handover the patient is given Penthrox. You wounder if Penthrox is superior to Entonox at reducing pain.

Search Strategy:

Conducted a literature search via PubMed and Google Scholar using the following search terms:

"Penthrox" AND "Entonox" AND "trauma" AND "methoxyflurane"

Outcome:

Collectively 185 studies returned which after removal of studies based on non-relevance according to their title, and after quick analysis, and discarding duplicates. 4 studies remained and included

Relevant Paper(s):

Study Title	Patient Group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
BET 1: Green or blue for you? Methoxyflurane (Penthrox) or nitrous oxide/oxygen 50% mixture (Entonox) for the management of acute pain in the ED Shah Mizanur Rahman, Eimhear Quinn 2019	Patients in acute pain secondary to traumatic pain	Case series CEBM 4	2 studies included with a total of 2208 participants	No evidence found to suggest superiority of methoxyflurane over Entonox and any other analgesic agents	One study was 1257 participants in labour not trauma patients. Other study does include 951 trauma patients. Both studies neglect to note the use of alternative analgesic agents or adjuncts such as ice, splinting or other analgesic medication. One study included was funded by pharmaceutical companies. No documentation of time of injury or onset of pain and time analgesia administered or with associated risks of injury complication. Both studies use self-reported pain scores introducing individual variation/subjectivity to results.
Management of trauma pain in the emergency setting: low-dose methoxyflurane or nitrous oxide? A systematic review and indirect treatment comparison Keith M Porter, Mohd Kashif Siddiqui, Ikksheta Sharma, Sara Dickerson, Alice Eberhardt 2017	Patients aged >18 with trauma induced pain in the per-hospital or hospital setting	Systematic Reviews and Meta-analyses CEBM 1a	4 randomized controlled trails used for analysis, with a further two being excluded after bias assessment. Leaving 2 studies included fir quantitative synthesis	The proportion of patients experiencing pain relief at 15 minutes after start of inhalation was greater under low-dose methoxyflurane, but statistical significance was not achieved. No significant differences between the two agents. Entonox is contraindicated in any condition where gas is entrapped within the body and where expansion might be dangerous. As a result Entonox has more contra-indications in trauma compared to Penthrox.	Small size of controlled trials 2. Different pain scales use over two studies that are not interconvertible
Evaluation of the effectiveness and costs of inhaled methoxyflurane versus usual analgesia for prehospital injury and trauma: non-randomised clinical study Murray D. Smith, Elise Rowan, Robert Spaight, Aloysius N. Siriwardena 2022	Adults with moderate to severe traumatic pain attended by ambulance staff	Systematic review / meta - analysis of case control study CEBM 3a	Comparison of the effects of the administration of the following at reducing pain: methoxyflurane 483 patients - 753 Entonox - 802 IV morphine. 278 patients using paracetamol	Methoxyflurane reduced pain more rapidly and to a greater extent than Entonox	Bias in the reporting of pain score by the ambulance staff reporting pain. Patients were also offered additional pain relief as well as methoxyflurane making the reported effects of methoxyflurane inaccurate.
Penthrox Is an Effective Analgesic but Is It Patient Approved? Ana V Dias, Ziad Zeidan, Matt Copp, Frances Eslabra, Rawan Hassan, Rory Middleton 2024	All users of Penthrox in the ED over a two month period	Case control observational study 3a	101 participants included within the study that was completed via questionnaire.	No direct comparison made.	Small patient group. Standard pain score not recorded, No direct comparison. Low quality study

Author Commentary:

It seems there has been very little studies completed that have explored the effectiveness of methoxyflurane in comparison to Entonox. It seems from the literature I have seen, there is no robust superiorities observed when using methoxyflurane for the treatment of acute traumatic pain when compared to Entonox. There is a suggestion that methoxyflurane may be faster acting and may work very well in balanced approach with the administration of additional analgesia.

Bottom Line:

There is currently very limited literature to conclude on whether methoxyflurane is superior at managing traumatic pain. Entonox is contraindicated in any condition where gas is entrapped within the body and where expansion might be dangerous. This is more prevalent in trauma patients. Methoxyflurane should be considered in situation where Entonox is contraindicated and used as part of a balance analgesia regime.

References:

Shah Mizanur Rahman, Eimhear Quinn. BET 1: Green or blue for you? Methoxyflurane (Penthrox) or nitrous oxide/oxygen 50% mixture (Entonox) for the management of acute pain in the ED
Keith M Porter, Mohd Kashif Siddiqui, Ikksheta Sharma, Sara Dickerson, Alice Eberhardt. Management of trauma pain in the emergency setting: low-dose methoxyflurane or nitrous oxide? A systematic review and indirect treatment comparison
Murray D. Smith, Elise Rowan, Robert Spaight, Aloysius N. Siriwardena. Evaluation of the effectiveness and costs of inhaled methoxyflurane versus usual analgesia for prehospital injury and trauma: non-randomised clinical study
Ana V Dias, Ziad Zeidan, Matt Copp, Frances Eslabra, Rawan Hassan, Rory Middleton. Penthrox Is an Effective Analgesic but Is It Patient Approved?