The Use of Inhaled Methoxyflurane (Penthrox) as an Analgesic for Acute Traumatic Pain and Painful Procedures​
Introduction​
This document sets out guidance on the safe paediatric use of Penthrox® (methoxyflurane), a potent, self-administered inhaled analgesic that provides rapid relief for moderate to severe pain. It belongs to the fluorinated hydrocarbon group of volatile anaesthetics and is unique among the group in having analgesic properties at low doses. It is effective for both trauma-related and procedural pain, allowing for reduced reliance on intravenous analgesia or sedation [1; 2] which is time and resource consuming as well as carrying additional risks.

In Southampton CED at present the 3 main options available when procedural sedation is indicated are intranasal Fentanyl, inhaled Entonox, or intravenous Ketamine (in addition to simple agents). Penthrox® as an alternative agent avoids the delay and pain associated with placing IV access and is not only effective but rapid in onset, with a short recovery time and does not require a high dependency area or continuous monitoring [3]. The Penthrox® inhaler allows the patient to titrate their analgesia to their pain and allows them continuous usage thus reducing requests for further pain relief.

This would benefit a busy overstretched CED, and evidence suggests result in a reduced length of stay [4], keep senior clinicians available for other tasks and above all give patients timely access to appropriate analgesia. Furthermore, Penthrox® has been shown to be a more environmentally sustainable option [5].

In the UK, it is not currently licensed for patients under 18; however, it has been safely used in paediatric populations in other countries for decades. Following successful implementation in other children’s hospitals in the United Kingdom and in line with existing evidence, we are introducing its use in children aged 5 years and older in Southampton for use ‘off-licence’.
Scope and Purpose​
This SOP applies to clinicians (doctors, nurse practitioners, and appropriately trained nursing staff) in CED. It is designed to guide the safe use of inhaled methoxyflurane (Penthrox®) for analgesia for acute traumatic pain and painful procedures in the children’s emergency department (CED). 

The target population is children aged 5 years and older who are developmentally able to understand and use the device. It would be indicated for:
  • Moderate to severe pain in conscious patients resulting from trauma (e.g. fractures, dislocations, burns, etc).
  • Procedural analgesia for painful interventions (e.g. fracture manipulation, wound care, or dressing changes)
Definitions
Penthrox® - is a compact, lightweight, hand-held inhaler containing an analgesic dose of methoxyflurane. It is self-administered under supervision of a person trained in its administration. It is currently licensed for adults and indicated for the emergency relief of moderate to severe pain in conscious patients with trauma and associated pain.  More information can be found here. 

Procedural sedation - Techniques and medications used to minimize anxiety and pain associated with unpleasant or painful procedures. More information can be found here.

Moderate or severe pain - Any pain which scores 4+ on the Faces Pain Scale - Revised (FPS-R), the Wong Baker Faces Scale or the FLACC behavioural pain scale.

Faces Pain Scale Revised / Wong Baker Faces Scale:

https://brandonkss.github.io/pain-chart-with-faces.html

Faces Pain Scale Revised / Wong Baker Faces Scale:

Merkel, S. I., Voepel-Lewis, T., Shayevitz, J. R., & Malviya, S. (1997). The FLACC: A behavioral scale for scoring postoperative pain in young children. Pediatric Nursing, 23(3), 293–297. The FLACC scale was developed by Sandra Merkel, MS, RN, Terri Voepel-Lewis, MS, RN, and Shobha Malviya, MD, at C. S. Mott Children’s Hospital, University of Michigan Health System, Ann Arbor, MI. Used with permission.
Restrictions
Methoxyflurane (Penthrox®) may only be given in adherence to this protocol, by a member of the CED staff, who has appropriate training in the assembly and administration of methoxyflurane via the Penthrox® device.
Exclusion Criteria
  • Hypersensitivity to methoxyflurane (or any fluorinated anaesthetic)
  • Malignant hyperthermia (in patient or relatives)
  • Head injury causing reduced consciousness (including due to alcohol)
  • Clinically significant renal and/or liver impairment
  • Respiratory depression
  • Recent use of methoxyflurane (not to exceed greater than a 6 mL dose in 24 hours and/or a total of 15mL per week)
  • Ensure patient is not taking CYP-450 enzyme inducers* (e.g. isoniazid, phenobarbital, rifampicin) and antibiotics with known nephrotoxic effect (gentamicin, tetracycline, colistin, polymyxin B, amphotericin B)

*Enzyme inducers may increase the rate of metabolism of methoxyflurane and thereby increase its potential
toxicity – CYP-450 enzyme inhibitors will not increase the risk of any potential toxicity
Precautions
  • Use with caution in patients with CNS depressants due to additive sedative effects.
  • Ensure activated carbon chambers are used to minimize occupational exposure.
  • Ensure patient/carer given advice on signs of (rare) developing nephro- or hepatotoxicity (see official patient alert card (appendix 4) and CED information sheet (appendix 3)
  • Use alternative analgesia for high intensity service users.
Adverse Reactions
Dizziness, drowsiness, euphoria, dysarthria, amnesia, anxiety, taste disturbance, headache, nausea, paraesthesia, hypotension, cough, sweating.

Adverse effects are generally CNS symptoms which are easily reversible with ceasing of the drug / titrating its use downwards. They may include dizziness, somnolence, headache, cough, euphoria and feeling drunk.

Serious dose-related nephrotoxicity has only been associated with methoxyflurane when used in large doses over prolonged periods during general anaesthesia.

If there are concerns about reduced consciousness, respiratory depression, or parental concern, inform a senior clinician immediately.
Preparation
Fasting
  • Not Required

Consent
  • Gain verbal consent after giving parents a patient information sheet (appendix 3) to read and answer any questions.

Equipment & Monitoring
  • Standard monitoring (Oxygen saturations & heart rate trace) and resuscitation equipment should be available.
  • Continuous monitoring is not required.
  • The Penthrox® device and 3ml vial of methoxyflurane are provided in one box and are stored in the Drugs cupboard.
  • Penthrox® should be self-administered by the patient under supervision of a person trained in its administration.
'How to use Penthrox' 
Select 'for HCPs'
Environment
  • The patient should be in an allocated CED cubicle.
  • It is not appropriate to be used in the waiting area.

Personnel
  • Any healthcare professional who has been appropriately trained on the assembly and delivery of the Penthrox® device may administer it once it has been prescribed.
  • Prior to first use the patient should be reminded that the first few inhalations are likely to cause a cough
  • The first few inhalations should be witnessed to ensure adequate technique, exhalation through the mouthpiece and to provide reassurance.

Methoxyflurane (Penthrox®) Dosage

One bottle of 3mL methoxyflurane to be vaporised in a Penthrox® inhaler. On finishing the dose, another 3mL dose may be used. A dose of 6mL should not be exceeded due to the risk of renal toxicity.

Onset of pain relief occurs at 6-10 inhalations. Patients are encouraged to inhale intermittently to achieve adequate analgesia. Continuous inhalation of a 3mL dose provides analgesia for up to 25-30 minutes. Administration on consecutive days is not recommended and the total dose to a patient in a week should not exceed 15mL.
Patient Alert Card Sticker
A Patient Alert Sticker (Appendix 4) will be given to each patient/parent/caregiver before discharge from the department. Completion of this step forms part of the checklist.

Practical Tips for use:

Go slow: “see double”:

Allow sufficient time for the drug to work as it varies from patient to patient from 6 breaths up to a few minutes of inhalation. Patients may describe ‘seeing double’ or become a bit disinhibited as they approach the appropriate level of analgesia.
Good Seal:

Ensure good seal around mouthpiece to reduce entrainment of air and dilution of methoxyflurane on inhalation / contamination of environment with exhaled methoxyflurane that has not been channelled through charcoal filter on exhalation. Patient must breathe in and out through the device.
Gentle first few breaths

Encourage patient to take gentle first few breathe while they get used to the smell/ taste of the drug. Then gradually deepen breaths (+/- cover dilutor hole) to attain sufficient analgesia for procedure.
In-Hold-Out:

Deep breaths in, hold in lungs for few seconds then exhale
Reassure/Suggestibility:

Patients can become disinhibited. They are often suggestible and will settle with reassurance and a calm environment
Patient feedback: stop-deepen-restart:

If the patient becomes uncomfortable, stop the procedure and deepen the analgesia by taking deep breaths with the dilutor hole covered. Advise the patient to take a deep breath in, to hold in the lungs for a few seconds, and then exhale.
Regular verbal contact with patient:

Remove inhaler form patients’ mouth if they seem to be getting too sedated - should recover rapidly
Staff:

It can be normal for staff to smell the drug slightly, but it should not be potent. If it is, ventilate the area. In either case it is highly unlikely staff can be exposed to enough of the drug to cause any effects.
Communication & Training Plans
Staff will undergo initial training on device use, patient selection, and drug specifics from a representative from the supplier (Galen). Staff already familiar with the device should cascade training to other staff on an opportunistic basis.
Process for monitoring compliance
The PIER network will review problems associated with this guideline through the governance process.

Compliance will be monitored by assessing the documentation of data collection via the checklist. Completion of the checklist will be audited by the CED team delivering Penthrox in each site.

The first 50 uses and / or 6 months of use in each department will be audited to review compliance with the checklist.

Any adverse reactions will be documented via the relevant data collection section on the checklist.

Reporting arrangements will also be communicated to the local Drugs & Therapeutics boards.
References​
  1. CoffeyF, WrightJ, HartshornS et al. STOP! a randomised, double-blind, placebo- controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. EMJ 2014;31:613-8.
  2. Hartshorn S, Middleton PM. Efficacy and safety of inhaled low dose methoxyflurane for acute paediatric pain: A systematic review. Trauma. 2019;21(2):94-102
  3. Jason C. Bendall, Paul M. Simpson & Paul M. Middleton (2011) Effectiveness of Prehospital Morphine, Fentanyl, and Methoxyflurane in Paediatric Patients, Prehospital Emergency Care, 15:2, 158-165
  4. Young L, Bailey GP, McKinlay JAC. Service Evaluation of Methoxyflurane Versus Standard Care for Overall Management of Patients with Pain Due to Injury. Adv Ther. 2020 May;37(5):2520-2527.
  5. GreenED Framework – Reducing your department’s environmental impact; Penthrox
Appendix 1 - Flowchart​
Appendix 2 - Checklist
Appendix 3 - Patient Advice Leaflet
Patients/Guardians can scan the QR code below to have the Information leaflet sent to their phones.
Appendix 4 - Patient Alert Card
Document Version: 
1.0

Lead Authors: 
Thomas Cromarty, UHS PEM Consultant
Beatrice Gardiner, UHS ST3 EM Resident
Keisha Kamalanthanan, RCPCH PEM Resident
Amanda Bevan, UHS Divisional lead Pharmacist
Approving Network:
Wessex Paediatric Emergency Medicine Network

Date of Approval: 
August 2025

Review Due:
August 2028