Core Skills — 23 February 2021 at 9:10 pm

Penthrox® and Pain

Dr Craig Miller / Emergency Medicine Trainee / South West

Far from help and faced with a patient in acute pain; what are your options for analgesia in the remote setting? Craig Miller is an Emergency Medicine and Expedition Doctor with experience ranging from high altitude to remote diving, and many environments in between. Craig discusses the rationale for including Penthrox® in his remote medical kit.

Approach to Pain in the Wilderness

The role of the expedition doctor begins long before arriving on-site, bags packed ready for the next adventure. Taking the time to thoroughly plan and familiarise yourself with your medical kit will help to lay the foundations for a successful expedition.

Analgesia in the wilderness can be challenging given the limited interventions available, both pharmacological and non-pharmacological, therefore it is important in the planning phase to consider the different options for pain management and anticipated aetiologies.

Many of us will be familiar with the WHO pain ladder which was initially designed for the management of cancer pain and has since been adapted for the management of acute pain of varying aetiologies. The Wilderness Medical Society (WMS) has adapted the ladder to create a ‘pain pyramid’ which forms the basis for their guidelines on the management of pain in the wilderness setting1 [Figure 1].

Figure 1. Pain treatment pyramid from the Wilderness Medical Society (WMS) guidelines1.

Severe Pain in the Remote Setting

Management of acute severe pain can be extremely challenging for the remote medic. Whilst opiate medications are often utilised for severe pain in the UK, having morphine or fentanyl in the expedition medical kit can be fraught with issues. Parental opiates are controlled drugs in the UK and accordingly remain subject to strict legislation on their supply, requiring an export license from the Home Office if they’re being taken overseas2. Transit and importation of opiates is similarly complex with different regulations for each country or territory. For example, UAE will not allow transit of opiates and these will be seized by customs3. Indonesia classifies codeine as a narcotic and requires appropriate licenses from various government agencies and police departments. Having spent six months on expedition in West Papua I’ve been exposed to the logistical and bureaucratic challenges of even the most simple paperwork; importing opiates in your medical kit would be no small feat. Even worse, there are extreme repercussions under Indonesia’s narcotics trafficking laws, with maximum punishment including the death penalty or life imprisonment4 – not a situation to be getting into. These barriers limit parental opiates to expeditions with significant logistical and organisational support. Thankfully, there are alternatives!

Penthrox® (Methoxyflurane)

Methoxyflurane is a volatile anaesthetic agent that can be used to treat moderate and severe pain. It was initially developed in the 1940s as a general anaesthetic, preferred over other agents for its cardiovascular stability and post-operative analgesic properties. Due to its analgesic properties at sub-anaesthetic doses, a disposable inhaler was initially developed for the management of pain during labour. Unfortunately, evidence of nephrotoxicity at high anaesthetic doses (upwards of 15 mL) was demonstrated and ultimately resulted in its removal from the market5. Australia and New Zealand continued to use methoxyflurane as an analgesic agent at much lower doses (3-6 mL) predominantly in the prehospital setting. Studies have demonstrated Penthrox® to be a safe and effective medication for pain management, with almost no risk of significant nephrotoxicity at low doses. Otherwise known as the ‘green whistle’, it is an alternative to parental opiates in the management of moderate to severe pain secondary to trauma in conscious adults.

Figure 2. Penthrox® (Methoxyflurane)

Using Penthrox®

Penthrox® is a portable and lightweight single-use inhaler that is used for the delivery of methoxyflurane. The kit contains one green inhaler device with an absorbent polypropylene wick and a vial containing 3 mL of methoxyflurane – you simply assemble the inhaler and charcoal scrubber, pour the liquid onto the absorbent wick and it’s ready to be used. The patient self-administers the medication by inhaling the vaporised liquid through the mouthpiece, enabling them to titrate administration and achieve adequate pain control. Rapid onset analgesia will begin within 6-10 inhalations from the 3ml vial, which will provide approximately 30 minutes of analgesia with continuous use, extending to 1 hour with intermittent use5. The maximum daily dose is 6ml, allowing for the administration of two vials over a 24 hour period. Note the maximum weekly dose of 15mL, ensuring that it is not used on consecutive days in order to limit the risk of nephrotoxicity.

Figure 3. The Penthrox® inhaler.

Side Effects and Contraindications

The side effect profile of Penthrox® is relatively modest with dizziness being reported as a very common side effect, followed by headache, somnolence, dry mouth and nausea, which are reported as common6. The self-administration of Penthrox® makes it simple for patients to reduce inhalations and limit side effects, whilst titrating for desired pain control. Contraindications are shown in Table 1, and helpfully there is a contraindication card included in the Penthrox® packs for the health professional and patient.

Table 1: Contraindications to Penthrox administration
Hypersensitivity to methoxyflurane
Personal or family history of malignant hyperpyrexia
Personal or family history of severe adverse reaction to inhaled anaesthetic agents
Patients who’ve suffered liver damage after previous halogenated anaesthesia
Clinically significant renal impairment
Altered level of consciousness
Cardiovascular instability
Respiratory depression

Benefits in the Remote Setting

By their very nature expeditions head into the wilderness with challenging environmental conditions. Ideal expedition medications are compact, lightweight, and durable with minimal side effects. With Penthrox® fulfilling these criteria the last important consideration is environmental stability. Penthrox® does not require specific temperature storage conditions and is stable even at low ambient temperatures. Again this is advantageous in comparison to nitrous gas which separates at low temperatures, meaning a hypoxic mix could be delivered to the patient. Wilkes et al. report the successful use of methoxyflurane at high altitude (4470m) for procedural sedation, demonstrating stability at altitude and extreme temperature7. Porter et al. report proven stability in temperatures ranging from –20°C to 40°C and suggest Penthrox® is “suitable for emergency situations in extreme environments”5.

Given the challenges surrounding opiates on expedition, including importation and supply as well as administration in austere environments (i.e. intravenous cannulation), methoxyflurane represents an excellent alternative in the management of severe pain8. Additionally, there is the advantage of inhalers being more compact and transportable than a nitrous cylinder.

Penthrox® is being used increasingly in Emergency Departments across the UK for the management of severe pain and procedural sedation, thus opportunities to use methoxyflurane in a controlled environment are increasing. The characteristics of methoxyflurane are ideal for use in the wilderness setting, representing an excellent alternative to opiates and Penthrox® is now a must for my expedition medical kit.


  1. Russell KW, Scaife CL et al. Wilderness Medical Society. Wilderness Medical Society practice guidelines for the treatment of acute pain in remote environments. doi: 10.1016/j.wem.2013.10.001. PMID: 24462332.
  2. Government Export License –
  3. UAE Transit Medications –
  4. Indonesia Narcotics Customs –
  5. Porter KM, Dayan AD et al. The role of inhaled methoxyflurane in acute pain management. Open Access Emerg Med. 2018;10:149-164. doi:10.2147/OAEM.S181222
  6. Penthrox EMC information –
  7. Wilkes M, Heath EC et al. Methoxyflurane for Procedural Analgesia at 4470 m Altitude. Wilderness Environ Med. doi: 10.1016/j.wem.2018.02.011. PMID: 30057014.
  8. Middleton PM, Simpson PM et al. Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting. doi: 10.3109/10903127.2010.497896. PMID: 20809687.