The main result of this life cycle analysis study on the materials and devices required for the administration of acetaminophen and ketoprofen is that the oral administration of these drugs is associated with a carbon footprint 53–67 times lower and requires eight to ten times less water consumption than their intravenous administration. In addition, the oral administration of these drugs is 16–18 times more cost-effective than their intravenous administration.

The results of the present study are in line with those of previous studies that assessed the estimation of CO2e emissions associated with the primary production materials and material disposal for intravenous acetaminophen in plastic bottles or in glass bottles, and oral acetaminophen in blister packs.24,25 These previous studies found ratio of CO2e emissions between oral acetaminophen in blister packs and intravenous acetaminophen in plastic bottles ranging from 8 to 43, depending on the system boundary and the location of dose, while intravenous acetaminophen in glass bottles was associated with much higher CO2e emissions.24,25

Switching perioperative intravenous to oral administration of acetaminophen and ketoprofen may be performed within the concept of pre-emptive or preventive analgesia.12,13 This concept is grounded on the hypothesis that administering analgesia prior to a painful stimulus can enhance pain management. According to the Enhanced Recovery After Surgery (ERAS®) guidelines,26 oral route for NSAIDs and acetaminophen should be used in place of intravenous administration whenever possible to enhance postoperative recovery, since both routes of administration have been shown to reduce the need for opioids.11,14,16 Human pharmacokinetic studies have shown that orally administered ketoprofen and acetaminophen are rapidly absorbed, with an over 90% absorption, and a duration of the analgesic effect lasting four to six hours.27,28 Thus, one can reasonably assume that preoperative oral administration of acetaminophen and ketoprofen can provide effective postoperative analgesia without the need for additional perioperative intravenous infusion for surgical procedures lasting less than three hours. The use of extended-release acetaminophen and longer acting oral NSAIDs could be appropriate in case of more prolonged surgical procedures. A concern is that the contraindications of these drugs must be respected, and caution may be required in patients treated with anticoagulants, in whom the risk of bleeding would be increased by treatment with NSAIDs, in which case the administration of oral cyclooxygenase-2 inhibitors may be preferred.

At the Hospices Civils de Lyon, more than 95% of the nearly 85,000 procedures performed in 2022 lasted less than three hours. If the perioperative intravenous administration of acetaminophen and ketoprofen were switched to oral premedication in 70% of these cases (when excluding the cases where no perioperative analgesia is required, oral premedication is contraindicated, or acetaminophen or ketoprofen are medically contraindicated), it could reduce greenhouse gas emissions by 25–31 tons of CO2e annually (depending on the scheme of intravenous administration), save 490,000–625,000 L of water per year, and result in a cost saving of EUR 86,000–98,000 (CAD 126,000–145,000) per year. Scaling this up to the national level, assuming around two-thirds of the 10 million surgical interventions in France could switch from an intravenous to an oral administration of drugs, the change could save 58,000–74,000 m3 of water each year and reduce greenhouse gas emissions by 2,900–3,700 tons of CO2e annually. This corresponds to greenhouse gas emissions from an average gasoline-powered passenger vehicle driving 18 million km (the equivalent of driving around the Earth 462 times).29

These benefits are probably underestimated since intravenous administrations of analgesic drugs performed daily in medical, emergency, and surgical departments are not considered in these estimates, although they could often also be done orally. Furthermore, we assumed that half a bottle of ketoprofen would be used for each patient, a practice that is possible in France but not in the USA where each vial should be used for only one patient.30 In this case, the first administration scheme would be associated with the emission of 466 g CO2e and 10.0 L water waste, and the second administration scheme would be associated with the emission of 578 g CO2e and 12.4 L water waste, further increasing the difference in environmental impact between intravenous and oral administration.

A major strength of the present study was that the impact of each analgesia strategy was also assessed in terms of water waste, a parameter that is frequently overlooked in studies focusing on the environmental effects of health care.2,5 The management of the scarcity of drinking water resources in relation to climate change will be one of the major challenges in the next decades.1 The results of the present life cycle assessment show that switching from an intravenous to an oral administration of drugs in only half of the surgical patients in France would save the equivalent of the annual domestic water consumption of 850 French people.

The findings of the present study thus highlight the significant environmental and economic impact that can result from making changes to the medical care provided to patients. The concept of sustainable design in health care encompasses a range of actions across different levels, including societal, health care facility, health care unit organization, care organization, and patient care levels. At the patient care level, health care professionals can promote sustainable health care by considering environmental impacts when selecting hypnotic medication,9,10 avoiding the use of nitrous oxide, streamlining preoperative warming indications and oxygen administration,6,8 and, as illustrated herein, by considering drug delivery methods.24 The results of this study could thus help encourage health care professionals evaluate their practices, enabling them to make changes that reduce the environmental impact associated with care in addition to saving money.

The present study has some limitations. The life cycle analysis did not consider the environmental impact of producing intravenous and oral acetaminophen and ketoprofen, although it may differ between these two formulations.25,31 A recent study showed that greenhouse gas emissions related to acetaminophen production, as only estimated from chemical reaction process modelling calculations, did not change substantially between oral and intravenous formulations, while the main change in greenhouse gas emissions between these two formulations was mostly related to devices, materials, transport and packaging.25 To date, no information on the life cycle analysis of ketoprofen is available. Further studies are needed to perform accurate life-cycle analyses of these oral and injectable analgesic medications25 to obtain a more accurate estimate of the impact of the choice of route of administration of these drugs on the environment. More generally, the environmental impact related to medication production should be considered when assessing the environmental impact of drug administration. Another limitation is that other environmental issues, such as air and water pollution associated with the production, transportation, and disposal of devices, were not studied. The use of infusion sets, syringes, and infusion bags containing polyvinylchloride exposes the environment to lead, mercury, dioxin, phthalates, and other endocrine disruptors.4 Thus, intravenous medications contribute to nonbiodegradable waste if sent directly to the landfill, and air, soil, and water pollution if incinerated. Switching from an intravenous to an oral administration of acetaminophen and ketoprofen may also reduce this pollution concern. Nevertheless, another point to consider is that large-scale changes in the administration methods of acetaminophen and ketoprofen could lead to additional environmental costs, related to the decommissioning of facilities and the construction of new facilities to meet the monumental shifts in demand; this concern needs to be qualified, however, by also considering that current plants could move towards the production of other intravenous drugs that are in demand, potentially addressing current medication shortages. Furthermore, the life cycle assessment was conducted from the perspective of a health care facility in France, considering the energy production and consumption patterns specific to that country, while the amount of CO2 emissions and water waste may differ significantly depending on the country and the energy sources used. Lastly, the environmental impact related to the transport of the devices and drugs could only be estimated, based on logistics assumptions, and was therefore somewhat imprecise. When performing life cycle assessment, transport modelling is a complex and data-intensive process, given the challenges and uncertainties in product supply chains related to modes of transport and distances. In the future, it will be necessary to have access to accurate logistical information to obtain more reliable data. Nevertheless, this information is usually considered confidential by companies and in some cases may not even be known to them.

In conclusion, the eco-audit conducted herein shows that the oral administration of acetaminophen and ketoprofen is associated with a much lower carbon footprint, less depletion of water resources, and lower costs compared with their intravenous administration. These results should encourage health care professionals to further evaluate the benefit of intravenous vs oral administration of these drugs for each patient and choose oral administration whenever no reasonable benefit can be gained from the intravenous alternative. These findings should also be considered when creating enhanced recovery protocols. The study also underscores the importance of considering the environmental impact of health care and to act for sustainable design in health care practices at different levels.