Nitrous Oxide

Each puff of a metered-dose inhaler expels a potent hydrofluorocarbon gas with upwards of 3,000 times the greenhouse warming potential of carbon dioxide. It is becoming more widely known that the healthcare sector is a significant contributor to greenhouse gas emissions, accounting for nearly 9% of the total in the U.S. But perhaps less recognized is that common substances routinely used in care—anesthetic gasses, even inhalers—are part of the problem.  Digging into the science, the irony becomes obvious: The mechanisms for keeping patients safe during a procedure or an asthma attack are also poisoning the environment. Desflurane, a common inhaled anesthetic, has heat-trapping properties hundreds to thousands of times greater than carbon dioxide. Meanwhile, nitrous oxide, a sedative used in surgery, has a warming potential 273 times that of carbon dioxide and greatly damages the ozone layer, which is crucial to absorbing harmful radiation from the sun. Even metered-dose inhalers that contain a seemingly small amount of hydrofluorocarbon gas have been shown to contribute meaningfully to emissions. At the end of last month, a small group of safety net hospitals and municipal health departments joined a 10-month collaborative in an effort to test decarbonization interventions and measure their results. The cohort, led by the Institute for Healthcare Improvement, includes sustainability professionals, clinicians and other healthcare leaders across six states. Each organization is expected to pick an improvement project and will receive support from experts and peers to carry it out. “For safety net hospitals who deliver care on tight margins and serve patient populations disproportionately impacted by the effects of climate change, investing in lowering carbon emissions holds the potential to advance their mission, strategy, and financial health,” the IHI said in its request for applications. The last IHI decarbonization cohort wrapped up in December 2023. More than a dozen organizations participated in 16 quality improvement projects. More than half measured reductions either in waste or purchases of anesthetic gas. Several sites decommissioned central nitrous oxide and eliminated desflurane from their operating rooms. Fierce Healthcare spoke to some of the participants about what they were able to achieve.   Thinking big by going small   Nitrous oxide, commonly used in dentistry, can be stored in one of two ways: in large centralized tanks that deliver the gas to operating rooms through piping, or in portable cylinder tanks. Choosing between the two might seem inconsequential. Indeed, one benefit of a centralized system is having to change the tanks less often. However, several hospitals around the world recently discovered that between 75% and 95% of their nitrous oxide leaks out through the central piping before it ever reaches the patient, wasting resources and polluting the atmosphere.  Addressing this waste was a goal for Northwell, which joined the last IHI decarbonization cohort. But to do so, the health system would need to figure out how the gas was being procured and used at its facilities. With more than 800 ambulatory sites and 20-odd hospitals, this would prove no small task.  “When you’re as big as we are, that was quite a challenge,” Teresa Murray Amato, M.D., VP of Clinical Sustainability and Resource Stewardship and director of geriatric emergency medicine at Northwell Health, told Fierce Healthcare. Amato started by looking for allies—“probably the best way to start,” she said—such as the head of anesthesia at her own hospital, who was really interested in sustainability. “Try to go for the easiest first,” Amato said.  As part of its emergency management work, Northwell works to ensure it has a three-day supply of essential resources. Keeping that in mind, Amato’s team decided to test if anesthesiologists would have enough nitrous oxide if they were to only use the portable tanks for three days. The clinicians recorded how long they used the gas and at what flow rates.  That information and anecdotal conversations revealed the gas was being used very infrequently, and Amato’s team extrapolated the use and determined that decommissioning centralized nitrous oxide systems would not negatively impact clinical practice. Spreading awareness of the environmental harms also reduced nonessential uses of nitrous oxide. For Northwell, eliminating the large tanks didn't mean getting rid of nitrous oxide altogether, it just consolidates resources in a more practical way. There are some cost savings too, though not as great as the enormous benefits to the environment. Even if someone left a portable tank open by accident and it leaked entirely, the impact would be a fraction of that of a centralized tank, according to Amato. “It’s such a simple solution, but it’s a challenge in a very large, highly matrixed organization,” Amato said. Armed with the success from this project, the proof of concept is now helping fuel other similar projects forward. “Now, everybody wants to be the next one to go,” Amato noted. Northwell’s new goal is to have almost no central tanks by the end of 2024.   The dark side of inhalers    To expel the medication, each puff of a metered-dose inhaler relies on a hydrofluorocarbon gas, a potent greenhouse gas with upwards of 3,000 times the warming potential of carbon dioxide. This gas contributes to climate change, which can lead to events that worsen asthma and in turn further drive up the use of inhalers. Though each inhaler seems small, 144 million were prescribed in the U.S. alone in 2020. And three-quarters of those contained the gas. In England, metered-dose inhalers have been found to represent 3% of total National Health Service carbon emissions, equal to the carbon emissions from all the electricity used by the NHS. “They actually have a pretty substantial contribution to healthcare’s overall environmental impact,” Gregg Furie, M.D., medical director for climate and sustainability at Brigham and Women's Hospital, told Fierce Healthcare.  Alternatives, like dry powder and soft mist inhalers, exist. This was an area Mass General Brigham wanted to tackle through the IHI collaborative. “We saw it as an opportunity to provide some structure to a project that we initially wanted to focus on,” Furie said.  The health system leaned on the institute's staff to learn how to bring a range of diverse stakeholders to the table. “There are way more stakeholders than you think there are,” Jonathan Slutzman, medical director for environmental sustainability at Mass General Hospital, told Fierce Healthcare. The collaboration also offered regular check-ins and a framework for accountability, which forced momentum internally, Slutzman added. Their goal was to reduce the overall share of metered-dose inhalers that are prescribed and to shift to alternatives where possible. They also hoped to raise awareness of the environmental impact of certain inhalers within the organization. They don't yet have concrete data on the project's outcomes to share. “This is not something that many practitioners are aware of,” Furie noted. “We are the ones who ultimately prescribe these devices… this is something that we feel we have real agency to do something about.” While the shift to alternative inhalers across the U.S. has been slow, Furie expects that to begin to change. That shift is being partly driven by increased scrutiny of the patent process and high prescription costs at the federal level. Apart from provider-driven efforts to move away from metered-dose inhalers, other solutions need to come from industry innovations and policy reform, per Furie. The FDA is studying the challenges of developing inhalers with a lower warming potential—but Slutzman believes the agency can be doing more to protect sustainability. One could argue that environmental impact should be a part of evaluating the safety of a drug, he said. “FDA should be able to encourage or make it easier for drug delivery devices that we know are environmentally better,” Slutzman said. “That would enable us to prescribe better inhalers.”   Centering climate as a broader priority    The idea for the collaboration began when the Agency for Healthcare Research and Quality commissioned IHI to develop a primer on decarbonization. IHI sought input from an expert panel, collaborating with the National Academy of Medicine and Health Care Without Harm to co-design resources along the way. “There are more and more organizations engaging in this area, which is very exciting and it is very important to ensure there is no duplication of efforts,” IHI Director Bhargavi Sampath, MPH, told Fierce Healthcare. Afterwards, the organization wanted to put the primer into practice by way of a collaborative, intended to inspire leader engagement, boost teams’ confidence and skills and build will across departments. “It really takes a very big group of people to do this work,” said IHI Project Director Becka DeSmidt.  Anyone looking for organizational buy-in on sustainability initiatives is advised to stress the potential for cost savings, the moral obligation to address the climate for patient health and that prioritizing such initiatives can help retain current or recruit future staff. “We’ve heard a lot from clinicians directly about how meaningful and engaging this work can be and clinician advocacy can be really powerful in helping an organization make these commitments,” DeSmidt told Fierce Healthcare. Two organizations participating in the collaborative successfully made the case for additional sustainability hires by leveraging the progress they were making on their projects as well as the cost savings they were seeing. Two others integrated clinical decarbonization metrics into their key performance indicators amid “the growing acceptance of integrating climate priorities into broader system strategies,” DeSmidt said. “Something we were really excited about was the promise of bringing climate more centrally into health system priorities,” Sampath echoed, “to advance some of the climate work that really needs to take place more locally at the frontline and with clinician leadership.”

The NMDA receptor, a type of glutamate receptor, plays a crucial role in the human body. It is primarily found in the central nervous system and is involved in various physiological processes such as learning, memory, and synaptic plasticity. Activation of the NMDA receptor allows the influx of calcium ions into neurons, which is essential for neuronal communication and the formation of new connections. However, dysregulation of NMDA receptor activity has been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Understanding the role of NMDA receptors is vital for developing therapeutic interventions targeting these conditions. NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans. The state of anesthesia they induce is referred to as dissociative anesthesia. Several synthetic opioids function additionally as NMDAR-antagonists. Some NMDA receptor antagonists, such as ketamine, dextromethorphan (DXM), phencyclidine (PCP), methoxetamine (MXE), and nitrous oxide (N2O), are sometimes used as recreational drugs. The discovery of NMDA receptor antagonists was a turning point in the prevention of nausea and vomiting associated with cancer chemotherapy. The first registered clinical use of NMDA receptor antagonists was for the treatment of emesis associated with cancer chemotherapy. In the 1980s, several peptide antagonists derived from substance P were the first NK1 receptor antagonists. The analysis of the target NMDA receptor reveals a competitive landscape with multiple companies actively involved in research and development. Viatris Inc., AbbVie, Inc., Takeda Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., Reckitt Benckiser Group Plc, Sanofi, Johnson & Johnson, Endo International Plc, Supernus Pharmaceuticals, Inc., Merz Beteiligungs GmbH, Otsuka Holdings Co., Ltd., Axsome Therapeutics, Inc., Lundbeck Foundation, China National Pharmaceutical Group Co., Ltd., Eisai Co., Ltd., Jiangsu Hengrui Pharmaceutical Group Co. Ltd., Daiichi Sankyo Co., Ltd., Teva Pharmaceutical Industries Ltd., Nichi-Iko Pharmaceutical Co., Ltd., and Shiono Chemical Co. Ltd. are among the companies growing fastest under this target. The highest stage of development is the "Approved" phase, with a focus on indications such as Common Cold, Cough, Pain, Alzheimer Disease, and Depressive Disorder, Major. Small molecule drugs are progressing rapidly, indicating intense competition around innovative drugs. China, the United States, Japan, and the European Union are the leading countries/locations in terms of drug development. The progress in China is particularly noteworthy. Overall, the target NMDA receptor shows promise for future development in the pharmaceutical industry. How do they work?NMDA receptor antagonists are a class of drugs that block the activity of NMDA receptors in the brain. NMDA receptors are a type of glutamate receptor involved in the transmission of signals between neurons. By antagonizing or inhibiting the NMDA receptors, these drugs can modulate the levels of glutamate, an important neurotransmitter, in the brain. From a biomedical perspective, NMDA receptor antagonists have been primarily studied and used in the field of neuroscience and psychiatry. They have shown potential therapeutic effects in conditions such as chronic pain, epilepsy, depression, and schizophrenia. By blocking NMDA receptors, these drugs can help regulate the excitatory signals in the brain, which may contribute to the improvement of symptoms in these disorders. It is important to note that NMDA receptor antagonists should be used under medical supervision due to their potential side effects and interactions with other medications. The specific mechanism of action and clinical applications of different NMDA receptor antagonists may vary, but they generally work by reducing the excessive activation of NMDA receptors and modulating glutamate signaling in the brain. List of NMDA receptor AntagonistsThe currently marketed NMDA receptor antagonists include: Bupropion Hydrochloride/DextromethorphanTetrandrineDonepezil Hydrochloride/Memantine HydrochlorideDextromethorphan Hydrobromide/Quinidine SulfateDextromethorphan Hydrobromide/GuaifenesinAspirin/Magnesium Carbonate/Dihydroxyaluminum AminoacetateBudipine HydrochlorideEsketamine HydrochlorideHuperzine AFelbamateFor more information, please click on the image below. What are NMDA receptor antagonists used for?NMDA receptor antagonists are primarily studied and used in the field of neuroscience and psychiatry. For more information, please click on the image below to log in and search. How to obtain the latest development progress of NMDA receptor antagonists?In the Synapse database, you can keep abreast of the latest research and development advances of NMDA receptor antagonists anywhere and anytime, daily or weekly, through the "Set Alert" function. Click on the image below to embark on a brand new journey of drug discovery!