This guideline covers the use of Penthrox (methoxyflurane) for analgesia in moderate to severe pain in acute trauma and burns

Analgesia for any patient should be considered relative to the nature and severity of pain as a multi-modal approach – see analgesic pyramid below

What is penthrox?

Penthrox (methoxyflurane 99.9%) is an inhaled vapour that is used for the relief of moderate to severe pain in conscious adults with acute trauma pain or burns. Penthrox is a fluorinated anaesthetic. However, it is used in significantly lower doses than required for a general anaesthetic, for the purpose of pain relief.

Penthrox delivers significant environmental benefit as compared to Entonox.


Penthrox is licensed for conscious adult patients (18 years and older) with moderate to severe pain (Verbal Analogue Scale (VAS) > 4) with traumatic injuries such as:

  • Fractures and/or dislocations
  • Lacerations
  • Burns
  • Chest injuries & Abdominal injuries (pneumothorax is not a contraindication)


  • Painful procedures related to such injuries e.g. chest drains


Penthrox is contraindicated in patients with atraumatic pain and patients with mild pain (VAS < 4)

Penthrox is contraindicated in children/anyone under 18 years of age

The ‘CHECK ALLL’ checklist should be used to screen for contraindications

  • CCardiovascular instability
  • HHypersensitivity to Penthrox or any fluorinated anaesthetic
  • EEstablished or genetically susceptible to malignant hyperthermia.
  • CConsciousness reduced due to any cause including head injury, alcohol or drugs
  • KKidney impairment* (clinically significant, eGFR<30) or nephrotoxic drugs (tetracycline, gentamicin, colistin, amphotericin, polymyxin B)
  • -----------------------------------------------------------------
  • AAge < 18 years
  • LLung/respiratory impairment* (anything which causes respiratory compromise or respiratory depression. A managed diagnosis is not a contra-indication)
  • LLiver impairment* (deranged LFTs or synthetic function) or CYP450 inducers (carbamazepine, isoniazid, phenobarbital, phenytoin, primidone, rifampicin)
  • LLast administration of Penthrox (maximum dose 6 ml (2 bottles)/24 hrs or 15 ml/7 days). Should not receive doses on consecutive days.

            *seek senior advice relating to kidney, lung, liver impairment contraindications

Further information is available from the Summary of Product Characteristics available at the emc.


Starting dose is one 3mL bottle Penthrox.

  • Onset of pain relief is rapid and should occur within 6 to 10 inhalations (wait 10 minutes after starting to ensure adequate analgesic level achieved for procedure, even if inhalation not continuous).
  • If stronger analgesia is required, patient can cover dilutor hole on the AC chamber with finger during use.
  • Continuous inhalation provides analgesia for 25 to 30 minutes.
  • Intermittent inhalation provides analgesia for one hour.
  • Patients should be encouraged to assess their own level of pain and titrate the amount of Penthrox inhaled for adequate pain control.

A second bottle (3 mL dose of Penthrox) can be given immediately, if needed. No further doses can be given.

Maximum doses:

6 mL (2 bottles) for a single episode

6 mL in a 24-hour period and it should not be administered on consecutive days.

15 mL in a 7-day period (week).


  1. Prepare product: follow the step by step guide that comes with the product to fill the single use inhaler
  2. Prepare patient: Penthrox is self-administered by patients under the supervision of a person trained in its administration. Explain the process to the patient. Self-administration of the medication ensures a self-limiting dose. When a partial anaesthetic dose is achieved, the patient’s hand will fall away, preventing further administration until sufficient recovery achieved to use again.
  3. Monitoring: is required: intermittent blood pressure, continuous oxygen saturations and heart rate (which can be derived from the oxygen saturation trace). The location of the department’s defibrillator should be known. The patient should lie on a bed or trolley, either with sides attached and elevated, or a person on either side, to stop them from falling off.
  4. Post-Treatment: A patient who has used Penthrox does not require post-treatment monitoring.

A patient alert card should be given to the patient. If the patient is likely to receive repeated doses, the patient must be given the patient alert card at the end to ensure previous exposure and timing is taken into consideration for subsequent doses.

Penthrox may have minor influences on a patient’s ability to drive, operate heavy machinery or perform an action requiring significant coordination, motor skills or responsibility. Patients should be advised not to perform these tasks if they are feeling drowsy or dizzy.

Top tips for successful administration

  • Careful patient selection. Inform the patient of the nature of the sedation and what to expect. Ensure ‘buy-in’ from them.
  • Good seal
    • Ensure the seal around mouthpiece is adequate to reduce entrainment of air and dilution of Penthrox and to avoid contamination of the environment with exhaled Penthrox.
  • Go slow
    • Allow sufficient time for Penthrox to work (at least 10 minutes); this varies from patient to patient from 6 breaths up to a few minutes of inhalation. Patients may describe ‘seeing double’ as they approach an adequate level of analgesia.
  • Gentle few first breaths
    • Encourage the patient to take gentle first few breaths whilst they get used to the smell and taste. Then gradually deepen the breaths with or without the dilutor hole to attain sufficient analgesia
  • 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.
  • Reassure
    • Patients can become disinhibited. They are often suggestible and will settle with reassurance and a calm environment. Maintain regular verbal contact with the patient.
  • Remove the inhaler from the patient’s mouth if they seem to be getting too sedated. They should recover rapidly.

When to stop

  • Penthrox should not be utilised for a period greater than 2 weeks duration
  • Patient request
  • Patient experiencing undue pain or distress
  • Development of cardiovascular instability, respiratory depression or unconsciousness
  • New derangement in renal or liver function tests
  • Hypersensitivity to Penthrox
  • Threshold of maximum safe dose achieved (6 mL/24hours or 15 mL/7days)
  • Analgesic requirement reduced sufficiently that Penthrox use no longer indicated
  • Malignant hyperthermia

Side Effects

Commonly patients may feel dizziness, nausea and it is worth noting that if not used as described there is an increased risk of nephro and hepato toxicity. For further information on side effects and cautions see SPC.

Pregnancy and breast feeding

Exercise caution with the use of Penthrox in pregnancy, especially in the first trimester, and in breast feeding.

Penthrox Clinical Record

Click here

Last reviewed: 31/03/2022

Next review date: 31/03/2025

Author(s): Consultant Emergency Department.

Version: 1.3

Approved By: TAM Subgroup of ADTC

Reviewer name(s): Consultant Emergency Department.

Document Id: TAM496