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Abstract
Background The NHS has the target of reducing its carbon emission by 80% by 2032. Part of its strategy is using pharmaceuticals with a less harmful impact on the environment. Nitrous oxide is currently used widely within the NHS. Nitrous oxide, if released into the atmosphere, has a significant environmental impact. Methoxyflurane, delivered through the Penthrox ‘green whistle’ device, is a short-acting analgesic and is thought to have a smaller environmental impact compared with nitrous oxide.
Methods Life cycle impact assessment (LCIA) of all products and processes involved in the manufacture and use of Penthrox, using data from the manufacturer, online sources and LCIA inventory Ecoinvent. These data were analysed in OpenLCA. Impact data were compared with existing data on nitrous oxide and morphine sulfate.
Results This LCIA found that Penthrox has a climate change effect of 0.84 kg carbon dioxide equivalent (CO2e). Raw materials and the production process contributed to majority of the impact of Penthrox across all categories with raw materials accounting for 34.40% of the total climate change impact. Penthrox has a climate change impact of 117.7 times less CO2e compared with Entonox. 7 mg of 100 mg/100 mL of intravenous morphine sulfate had a climate change effect of 0.01 kg CO2e.
Conclusions This LCIA has shown that the overall ‘cradle-to-grave’ environmental impact of Penthrox device is better than nitrous oxide when looking specifically at climate change impact. The climate change impact for an equivalent dose of intravenous morphine was even lower. Switching to the use of inhaled methoxyflurane instead of using nitrous oxide in certain clinical situations could help the NHS to reach its carbon emission reduction target.
- analgesia
- emergency departments
- pain management
Data availability statement
Data are available on reasonable request. Complete input/output flows for OpenLCA can be found in online supplemental appendix 3. Raw data output from OpenLCA have not been submitted to the journal and can be made available on reasonable request.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Nitrous oxide is frequently used for analgesia but has significant environmental impacts.
Inhaled methoxyflurane can be used as an analgesic agent in certain clinical settings.
WHAT THIS STUDY ADDS
This life cycle impact analysis calculates the overall environmental impact of the currently available form of methoxyflurane, Penthrox.
Penthrox was found to have lower climate change impact by a factor of 117.7 for equivalent use of Entonox (nitrous oxide:oxygen, 50%:50%).
Morphine has the lowest climate change impact of the three analgesic agents.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
This type of analysis allows healthcare professionals and managers to make more informed decisions regarding procurement and delivering care, taking environmental impact into account.
The findings suggest a shift in the type of short-term analgesia used by clinicians to agents that are less harmful to the environment.
Background
The climate crisis is a health crisis. A recent report by Lancet Countdown, which tracks progress on health and climate change, discusses the unequivocal contribution that ill-health and healthcare makes to rising global temperatures and vice versa.1 In line with UK Government ambitions described in the Climate Change Act 2008, the Paris Agreement 2016 and the most recent Health and Social Care Act 2022 NHS England has set ambitious targets for carbon reduction.2–4 The first goal is reducing NHS England’s prepandemic carbon emissions of 25 megatonnes of carbon dioxide equivalents (MtCO2e)—around 5% of England’s carbon footprint—by 80% by 2032.5 Of these 25 MtCO2e, 2% is attributable to anaesthetic gases.6 Two recommendations are to be implemented to reduce these significant emissions: (1) altering clinical practice pertaining to prescribing and (2) administering and disposing of anaesthetic gases.
Nitrous oxide (N2O), is a commonly used anaesthetic gas in EDs in the UK and elsewhere.7 Inhaled methoxyflurane can also be used in acute emergency care for analgesia during painful procedures and is superior in managing pain from trauma compared with standard analgesic treatments.8 9 It is also thought to have a smaller overall environmental impact compared with N2O. We know that N2O has a 100-year global warming potential 66.25 times greater than methoxyflurane (N2O: 265, methoxyflurane: 4) and is one of the six major greenhouse gases targeted by the Kyoto Protocol, however, the overall environmental impact of methoxyflurane is unknown.10
The overall environmental impact can be calculated by carrying out a life cycle impact assessment (LCIA). The cradle-to-grave methodology of LCIAs calculates much more than the commonly measured ‘carbon footprint’, which only considers the carbon dioxide equivalent (CO2e). LCIA is a scientific method used to measure the entire environmental impact of a product or process, from raw material acquisition—the ‘cradle’—through its manufacture, transport and use, to product disposal—the ‘grave’.
The primary aim of this project is to carry out an LCIA of the currently available formulation of methoxyflurane, Penthrox, also known as the green whistle. The secondary aim is to compare the climate change impact of Penthrox with that of N2O.
Methods
We carried out an LCIA on Penthrox in July 2022. We have summarised the LCIA process into three steps (figure 1).
Steps for conducting the life cycle impact assessment (LCIA). Step 1: dismantling Penthrox into its component parts and weighing these. The figure shows the Penthrox device along with a 3 mL vial of methoxyflurane in the top box. The methoxyflurane drug is represented by the tablet. Step 2: arrangement of each component part into flows with LCIA software. In the figure an example flow is shown. Step 3: data analysis.
Step 1: dismantling the Penthrox device into component parts and weighing each part. Each part was made of one material, and this was cross-referenced with data sent by the manufacturer.
Step 2: entering data into LCIA software using ‘flows’. A flow consists of all inputs (raw materials, processes, transport and energy requirements) and outputs (waste disposal and excretion of drug) corresponding to each part of Penthrox. In figure 1 an example flow is shown. The flow is for the charcoal filter case which has the inputs of ‘polycarbonate’ as the raw material required for making the charcoal filter case and ‘injection moulding’ as the process required to make the charcoal filter case from the polycarbonate. The output of this flow is ‘hazardous waste incineration’ as at the end of the life cycle of Penthrox, it is assumed that the device will be thrown in the hazardous waste bins and incinerated. All inputs and outputs for this flow are 19.4 g as that is the weight of this component. A full list of all flows with inputs and outputs are listed in online supplemental appendix 1.
Supplemental material
Step 3: results and data analysis as provided by the LCIA software.
Functional unit
The unit measure in this study was one unit of Penthrox with 3 mL of methoxyflurane 99.7%, equivalent to 30 min use. The UK product version assessed in this study includes a charcoal filter and alert card. Southampton General Hospital was used as the end destination.
System boundaries
The ‘system boundary’ considered in this project is summarised in figure 2. This includes the manufacture of all physical components and drugs through to assembly, transport, use and disposal of the product. All components were searched for on Ecoinvent V.3.8, an LCIA inventory database.11 This is important for any LCIA project as the software running the analysis, in this project’s case, OpenLCA, draws on an LCIA inventory database for its data on previously logged LCIAs on various materials, products and processes, which have used a standardised framework for their calculation.12 Where a product or process is missing from Ecoinvent, an appropriate substitute can be used, or, as occurred in this project with the drug methoxyflurane, more analysis is required to fill this gap.
System boundaries for Penthrox. The system boundary shows the ‘cradle-to-grave’ analysis of the life cycle impact assessment. This is a simplified representation of all ‘flows’ shown in online supplemental appendix 3. *The manufacture of methoxyflurane from its raw materials has been considered as a separate process from other raw materials in the results to allow for contribution analysis.
Supplemental material
Mechanism of drug synthesis
Methoxyflurane had no matching record in Ecoinvent, therefore, potential reaction processes were searched for online. Three reactions are required to manufacture methoxyflurane (online supplemental appendix 2) and were considered in the LCIA.13–15 Bond energies were used to determine the energy change within each reaction. If energy was required, it was input into the LCIA as electricity demand and if energy was released it was listed in the LCIA as steam output. The by-products from reaction 2 were unclear from source material, therefore, assumed products were 1,1-dichloro-2,2-difluoroethylene, dichloromethane and water.
Supplemental material
Methoxyflurane is distributed/manufactured by Medical Developments International Limited (MDI) based in Victoria, Australia. It was assumed that the drug was manufactured on site at Scoresby Manufacturing facility in Melbourne, Australia, as this information was not available. An MDI representative provided information on the energy source at the Scoresby Manufacturing facility, explaining that the company has installed a solar array providing 750 MW of electricity, which was considered in the LCIA.16
Product manufacture
Component part and weight information was gathered from the manufacturer in June 2022.16 Manufacturing processes involved within the production of Penthrox were assumed and energy requirements of the machines involved within these processes were correlated with online literature.17
Transportation
MDI provided information on transport logistics of Penthrox.16 The end location used in this project was University Hospital Southampton, UK. Road distances were calculated using Google Maps and shipping distances were calculated using www.ports.com.18 19 Modes of transport include by truck and ship and appropriate fuel types were assumed. Summary of transport data is shown in online supplemental appendix 3.
Use
Penthrox requires no additional components for its use. The 3 mL vial of methoxyflurane is emptied into the chamber containing the wick. The user then forms an oral seal around the mouthpiece and inhales. They then exhale back into the device, where the valve causes the exhaled gases to pass through charcoal. Perfect technique, as guided by the manufacturer, was assumed in our analysis. Around 35% of the inhaled methoxyflurane is exhaled unchanged with the rest absorbed by the body. The exhaled methoxyflurane is captured by the charcoal, reducing the exhaled concentration of methoxyflurane to the environment to zero, as described by the manufacturer.16 This project assumed complete patient compliance with the instructions of exhalation into the device and 100% effectiveness of the charcoal.
The literature is less clear about the exact outcome of the 65% of 3 mL methoxyflurane that is absorbed by the human body. Studies have shown the metabolised products to be organic fluorine, fluoride and oxalic acid (29%, 7.7% and 7.1%, respectively).20 For the purposes of this study, the remaining 21.2% of methoxyflurane is assumed to be excreted unchanged.
Disposal
Although many component parts of Penthrox are easily recyclable, experience shows that the practicalities of recycling in clinical environments makes this unlikely to happen. For the purposes of this project, and the likely real-life disposal after use, all components were assumed as being discarded into hazardous waste bins and incinerated.
Data analysis
Data from Ecoinvent were modelled and analysed in OpenLCA. Table 1 includes both the impact category results and the LCIA methods used within this study alongside a description of each category. Contribution analysis of different parts of the LCIA was also assessed using five distinct areas: raw materials, methoxyflurane manufacture, production processes, transport and disposal. OpenLCA also calculated the normalised impact and disability-adjusted life years (DALYs).
LCIA results of Penthrox
Comparative analysis of Penthrox
No complete LCIA was currently available online for N2O. Climate change impact was available online for Entonox.21 Data from the study by Pearson et al were extrapolated to represent 30 min continuous use of Entonox at a minute volume rate of 14 L/min.
Climate change impact data were available for intravenous 100 mg in 100 mL morphine sulfate.22 A comparative dose of intravenous morphine sulfate to 3 mL of methoxyflurane in trauma is 0.1 mg/kg as shown by Mercadente et al.9 For the comparison, an adult weighing 70 kg was used. We assumed that the remaining morphine is not discarded. Data from Ecopassenger.com for CO2e of different types of transport between Newcastle upon Tyne and London was also gathered.23
Results
The 16 impact category raw results of the LCIA of Penthrox are presented in table 1, with initial overarching broad categories, corresponding descriptions, units and LCIA methods.
Contribution analysis
Figure 3 shows a contribution analysis for each impact category. Across 15 of the 16 impact categories, raw materials and the production process contributed to most of the impact. For the ozone depletion category, methoxyflurane manufacture contributed 98% of the ozone layer depletion impact due the assumed use of tricholoromethane in reaction 1 of manufacturing methoxyflurane (online supplemental appendix 2).
Percentage contribution analysis of life cycle impact assessment (LCIA) of Penthrox. The graph shows how impact of five separate parts of the LCIA (raw materials, methoxyflurane manufacture, production process, transport and disposal) contribute to the impact across the 16 impact categories described in table 1. Methoxyflurane manufacture is considered as a separate category to raw materials and production process.
Specifically for climate change impact, the highest contributing parts of the life cycle assessment of Penthrox were raw materials (34.40%) and the production process (29.81%). The lowest contributing categories were transport (3.28%) and manufacture of drug (6.52%) with disposal contributing around a quarter of the impact (25.97%).
Normalised impact
A normalised impact of 1.0 would represent the environmental impact expected for one person in 1 year in the respective category. The normalised impact is another way in which different LCIAs can be compared for different products. Freshwater eutrophication has the largest normalised impact (figure 4).
Normalised impact of Penthrox across impact categories.
Disability-adjusted life years
The analysis delivered DALYs for eight impact categories. Global warming was the greatest contributor (7.79E-07, representing 83.49% of total DALY impact) and the second largest contributor was water consumption (DALY: 1.50E-07, 16.08% of total DALY impact).
Comparative analysis of Penthrox
Using the climate change impact result from table 1, a comparison with an equivalent dose of Entonox and morphine sulfate could be made from other sources (figure 5)21 22; 117.7 times more CO2e is produced when Entonox is used (raw value 98.89 kg CO2e) compared with Penthrox (0.84 kg CO2e). Intravenous morphine (7 mg) produces 0.01 kg CO2e. For perspective, a plane journey from Newcastle Airport to London Heathrow Airport produces 120.2 kg CO2e, a train journey from Newcastle Central Station to London King's Cross produces 23.1 kg CO2e and a car journey from Newcastle Central Station to London King's Cross (distance 441.6 km), with a single passenger, in a gasoline conventional, produces 80.3 kg CO2e. These values are represented in figure 5.
Comparison of climate change impact of Penthrox and other analgesics. Other analgesics include Entonox continuous use for 30 min at rate of 14 L/min and 7 mg of 100 mg in 100 mL morphine sulfate. In addition to this, we have included comparative data for a flight, car journey and train journey between Newcastle and London.
Discussion
This detailed LCIA has calculated the environmental impact of Penthrox over 16 impact categories. This allows all those involved with its manufacture and use to fully understand its environmental impact and allows for comparison with other analgesics.
When considering any healthcare intervention, we should consider the environmental (planet), financial (profit) and social/clinical/therapeutical (people) element, the so-called triple bottom line of sustainable healthcare. Each of these will be discussed in turn.
Environmental impact
Factors such as the environmental harm should be considered by clinicians when deciding on which agent to use.24 This detailed LCIA has shown that Penthrox is better, from a climate change impact perspective by a factor of 117.7, than using 30 min of Entonox.21 23 Another advantage of inhaled methoxyflurane is that it is not delivered by a potentially wasteful pipe system. Multiple NHS hospitals report millions of litres of annual N2O leakage, totalling up to 95% of the total annual collective volume.25
Opioid analgesics might be considered in some scenarios where methoxyflurane could also be used, such as in trauma. For a 70 kg adult requiring 7 mg intravenous morphine, the climate change impact would be 0.01 kg CO2e. Furthermore, Pearson found two doses of intramuscular morphine to have a climate change effect of 0.08 kg CO2e, a similar impact to Penthrox. No data for comparing equivalent doses of intramuscular morphine and methoxyflurane on analgesic effect were found online. From these studies, we can appreciate that morphine has a lower carbon footprint. This could be a factor to consider when deciding which analgesic to use, while also acknowledging that time to peak effect of intravenous morphine is longer (15 min compared with 9 min for methoxyflurane) and has its own side-effect profile.9
Financial impact
The procurement and additional equipment costs of use of 3 mL unit of Penthrox, Entonox and intravenous morphine were £18.89, £6.60 and £7.70, respectively.26 The disparity in price between these products means that fiscally focussed health services may find it difficult to move from the cheap cost of N2O and morphine products to the more expensive single unit Penthrox dispenser. However, large healthcare trusts have significant market sway over procurement contracts, and there is a potential deal to be done on bulk purchasing pharmaceuticals with a smaller environmental impact.
Social (clinical) impact
Current evidence suggests that both N2O and methoxyflurane are good options for acute pain in the ED when compared with placebo pain management, with neither showing superiority.27 Both drugs are in regular use worldwide in prehospital care, community health, dentistry and in hospitals. However, N2O is still used far more than methoxyflurane, despite its large carbon footprint.10
Both are self-administered, self-titrated and non-invasive inhalational agents which are well tolerated with similar onset times for analgesia. Methoxyflurane is easily administered via a handheld device whereas N2O can be more difficult with either a heavy cylinder or a piped supply being required as well as a demand valve. Morphine has the added benefit of being available in multiple different formats so that it can be administered in the most appropriate form for the clinical picture.
Although the comparative environmental footprint of Penthrox is low, manufacturers should look at ways of delivering it more sustainably. Penthrox has many different types of plastic, as is evident from figure 2. If plastic recycling was widely available in healthcare settings, it would have to be clear which uncontaminated parts could be recycled safely. Further research and discussion with the manufacturer, local recycling contractors and clinicians would help to clarify this.
Limitations
As with any life cycle assessment system boundaries must be set and made clear at the outset, the quality of the data needs to be measured and any assumptions or limitations defined. Data cannot always be obtained from manufacturers so that best estimates must be used, and this methodology is both time consuming and costly. This was most evident for the manufacture of methoxyflurane as no data existed for it in Ecoinvent. The reactions required to make methoxyflurane were assumed according to the best available information online. We also assumed energy consumption in the filling and capping elements of production. The best available information online for this was sourced.
The assumption that patients will use Penthrox with perfect technique is unlikely to be true in all cases. Patients using the device are likely to be in pain or distress and remembering to exhale back into the device in these conditions is questionable. Finally, the assumption that all material was incinerated was anecdotal evidence from our own experience working in healthcare.
This type of detailed LCIA is now considered to be the industry standard and although it is laborious and by no means perfect, it is a far superior methodology to other so-called ‘carbon footprints’ as these only focus on one environmental impact category, the greenhouse gas emissions. An LCIA can take into account other impact categories such as land use, water use and ocean acidification. As such, a carbon footprint is only part of the full LCIA. The International Organisation for Standardisation (ISO) has provided guidelines and requirements for conducting an LCIA through ISO 14040 and ISO 14044.28 29
The challenge for healthcare generally is to incorporate these standards into our efforts to reach net zero as they provide the best quality data by which to make and monitor changes to our practice. At present, too many healthcare studies do not provide the full picture of environmental impact for our pathways and processes.
Conclusion
As the effects of climate change become more apparent, the need to make healthcare sustainable become increasingly urgent. If the NHS is to reach its ambitious target of an 80% reduction in carbon emissions by 2032, then healthcare professionals must start making choices on the drugs and equipment that they use, based on rigorous scientific evidence such as that presented in this study. This study has shown that low-dose methoxyflurane and morphine are more sustainable in terms of their relative climate change impact compared with N2O. Therefore, the authors urge readers to consider using methoxyflurane or morphine rather than N2O if it is safe to do so.
Data availability statement
Data are available on reasonable request. Complete input/output flows for OpenLCA can be found in online supplemental appendix 3. Raw data output from OpenLCA have not been submitted to the journal and can be made available on reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
Not applicable.
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Handling editor Caroline Leech
Contributors AM led the project, collected and analysed the data and drafted and revised the paper. He is guarantor. DM initiated the collaborative project and drafted and revised the paper. TC drafted and revised the paper. AF-W assisted with data analysis and drafted and revised the paper. BD assisted with data collection tools and data analysis, drafting and revision of the paper. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.