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Self-administered Inhaled Painkiller Shows Superiority in Prehospital Setting

A new study has revealed an inhaled analgesic recently introduced to the UK is the most effective form of severe pain relief in the prehospital setting following traumatic injury, in terms of speed of pain reduction.1

Treatment during the first hour after trauma is vital to improve patient survival and good analgesia can result in easier injury management and the potential to avoid chronic pain development.2,3 Despite this, less than a third of people in UK ambulances are given appropriate pain relief.4

The year-long MAPIT study, led by Professor Aloysius Niroshan Siriwardena of the University of Lincoln, UK, and carried out by East Midlands Ambulance Service, showed that the analgesic Penthrox®▼ (methoxyflurane), acts more than three times quicker than the most frequently used – and also inhaled – analgesic, Entonox® (gas and air), more than three times quicker than intravenous paracetamol, and twice as quick as intravenous morphine to reduce severe pain.1

Methoxyflurane, which has been dubbed the ‘green whistle’ has already been proven to be a convenient and effective option for pain relief, leading to a significant reduction in time spent in the hospital emergency department. Although it is used regularly in UK emergency departments, it is not widely used in ambulances.5-8

The data from the MAPIT study, was today (Tuesday 23rd March) shared at the 999 EMS Research Forum Annual Conference, providing the first comprehensive UK comparison of analgesic options used by paramedics and emergency medical technicians.1 The evidence means prehospital emergency staff can now feel confident when choosing methoxyflurane as a first-line treatment option for moderate-to-severe trauma pain.

Rapid and effective pre-hospital analgesia has the potential to improve the patient journey end-to-end. With the NHS continuing to face an exceptional crisis following the outbreak of COVID-19 and unprecedented levels of pressure to free up resources across all treatment settings, the study results are welcome news.1-3

Chief Investigator, Professor Aloysius Niroshan Siriwardena, commented: “There are many barriers to adequate pain relief. This study is the first to compare methoxyflurane with all other commonly used analgesics in the prehospital setting and the superior results add to the weight of positive findings from other UK and European hospital studies.

“From an academic perspective, it is an important addition to the evidence, and we look forward to seeing how greater uptake impacts patients in other ambulance trusts.”

Dr Leon Roberts, Medical Director for East Midlands Ambulance Service NHS Trust, which carried out the study, commented: “Rapid and effective pain relief is undeniably important in the prehospital setting and this study shows that emergency care staff have access to a well-tolerated treatment, which is easy to administer. EMAS is proud to be a leading organisation in prehospital research collaborating with key partners such as the University of Lincoln, who has analysed and evaluated this data.”




Notes to editors:

About Penthrox (methoxyflurane)

Methoxyflurane is a rapidly-acting inhaled analgesic agent which is self-administered by patients under the supervision of a person trained in its administration. It is easy to administer, with a well-tolerated safety profile, and has been proven to rapidly provide effective analgesia and potentially reduce patient length of stay in hospital settings.8-11

Methoxyflurane has been used extensively in Australia and New Zealand as emergency analgesia for almost 30 years and is licensed in a number of European countries for the emergency relief of moderate-to-severe pain associated with trauma in conscious adult patients.12,13

Penthrox consists of a green-coloured tube containing a fixed measure of methoxyflurane and can provide up to 60 minutes of pain relief per treatment. It is marketed in the UK by the pharmaceutical company Galen Ltd. 10

About the MAPIT study

A study investigating the clinical effectiveness and cost of using methoxyflurane for moderate-to-severe trauma pain relief in prehospital patients was carried out by the East Midlands Ambulance Service National Health Service (NHS) Trust over a 12-month period. The study was funded by Galen Ltd, but study design and analysis were carried out independently of the funder who had no role in the conduct or analysis of the research or preparation of the manuscript.1

The results showed that estimated time to relieve patients from severe pain (in each case, p<0.001) with use of methoxyflurane was 9.66 minutes compared to 37.53 minutes when using intravenous (IV) paracetamol; 10.47 minutes compared to 20.09 minutes when using IV morphine; and when compared to ‘gas and air’ (Entonox), 10.54 minutes for methoxyflurane whereas patients on Entonox were not predicted to exit a state of severe pain at the time of cut-off.1

About the University of Lincoln:

The University of Lincoln has been crowned Modern University of the Year in The Times and Sunday Times Good University Guide 2021. Its Gold award in the national Teaching Excellence Framework (an independent assessment of teaching quality in UK higher education) reflects the exciting teaching and great support available for students. The institution is known for a pioneering approach to working with employers, which has been recognised with a Lord Stafford Award and Times Higher Education Award. More than half of Lincoln’s research is judged to be internationally excellent or world leading (Research Excellence Framework).

About the East Midlands Ambulance Service

The East Midlands Ambulance Service provides emergency 999 care and telephone clinical assessment services for a population of 4.8 million people in Nottinghamshire, Leicestershire, Rutland, Northamptonshire, Lincolnshire and Derbyshire, receiving over one million emergency and urgent calls every year and equating to one call every 40 seconds.14

Volunteer ambulance staff from four ambulance stations in EMAS were first recruited to take part in training for administration of Penthrox and have since been using Penthrox for over two years (since October 2018).1



  1. Smith M, Rowan E, et al. Evaluation of the effectiveness and costs of inhaled methoxyflurane versus usual analgesia for prehospital injury and trauma. Presented at 999 EMS Research Forum Annual Conference, March 2021
  2. Chambers J, Guly H. The need for better pre-hospital analgesia. Archives of Emergency medicine. 1993;10: 187-192
  3. Friesgaard K, Riddervold I, et al. Acute pain in the prehospital setting: a register-based study of 41,241 patients. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2018;26(53)
  4. Siriwardena AN, Shaw D, Bouliotis G. Exploratory cross-sectional study of factors associated with pre-hospital management of pain. J Eval Clin Pract 2010; 16(6): 1269-75.
  5. Fabbri A, Ruggiano G, Garcia Collado S, et al. Role of inhaled methoxyflurane in the management of acute trauma pain. J Pain Res 2020;13:1547-55.
  6. Porter KM, Siddiqui MK, Sharma I, Dickerson S, Eberhardt A. Management of trauma pain in the emergency setting: low-dose methoxyflurane or nitrous oxide? A systematic review and indirect treatment comparison. J Pain Res. 2018;11:11-21.
  7. Xia AD, Dickerson SL, Watson A, Nokela M, Colman S, Szende A. Evaluation of pain relief treatment and timelines in emergency care in six European countries and Australia. Open Access Emerg Med. 2019;11:229-40.
  8. Young L, Bailey G, McKinley J. Service evaluation of methoxyflurane versus standard care for overall management of patients with pain due to injury. Adv Ther. 2020;37(5):2520-2527.
  9. Royal College of Emergency Medicine Best Practice Guidelines; Management of Pain in Adults. 2014 [Last accessed: March 2021].
  10. Penthrox (methoxyflurane) Inhalation Product Information. Available at: [Last accessed: March 2021].
  11. Mercadante S, Voza A, Serra S, et al. Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA). Adv Ther. 2019; 36(11):3030-3046.
  12. Marinangeli F, Reggiardo G, et al. Prospective, Multicentre Trial of Methoxyflurane for Acute Trauma-Related Pain in Helicopter Emergency Medical Systems and Hostile Environments: METEORA Protocol. Adv Ther. 2018; 35:2081–2092.
  13. Forrest M, Porter K, van der Velde J. Methoxyflurane (Penthrox ®)—a case series of use in the prehospital setting. J Paramed Pract. 2019;11(2):54-60.
  14. National Ambulance Research Steering Group. East Midlands Ambulance Service. Available at: [Last accessed: March 2021].
Self-administered Inhaled Painkiller Shows Superiority in Prehospital Setting

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Last Updated: 24-Mar-2021