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.”

SAN DIEGO, Nov. 7, 2023 /PRNewswire/ -- Hillhurst Biopharmaceuticals, Inc. ("Hillhurst"), a clinical-stage biopharmaceutical company focused on developing liquid drug products containing therapeutic gases, today announced the award of an up to $5 million HEAL (Helping to End Addiction Long-term®) Initiative grant from the National Institutes of Health. The NIH HEAL Initiative funds research to find scientific solutions to the opioid public health crisis. The initial $2 million award will fund the preclinical development, and, if awarded, an additional $3 million will fund the clinical development through a Phase 1 clinical study of HBI-201, an oral nitrous oxide therapeutic candidate for patients with sickle cell disease (SCD). HBI-201 is targeted for the treatment of acute pain associated with vaso-occlusive crises (VOC) in SCD. Hillhurst is collaborating on the preclinical portion of this project with Don Simone, Ph.D, and John Belcher, Ph.D., both Professors at the University of Minnesota, whose labs will test HBI-201 in mouse models of SCD pain. "With this award, the NIH HEAL Initiative enables further development of HBI-201with the objective of addressing a significant unmet need for non-opioid pain medications for patients with sickle cell disease," said Andrew Gomperts, Hillhurst's Chief Executive Officer. "We believe our novel approach of oral delivery of the analgesic nitrous oxide, approved for use by inhalation, holds great promise for these patients." About Sickle Cell Disease Sickle cell disease is a genetic disorder that is characterized by recurrent, unpredictable acute pain episodes associated with VOCs. Opioids are one of the primary means of symptomatic management of acute SCD pain, but have substantial drawbacks such as hyperalgesia, tolerance, and potential dependence. About HBI-201 Hillhurst's product, HBI-201, is an oral drug product candidate of nitrous oxide (N2O), with an administration route designed to enable the home use of N2O for patients suffering from pain associated with VOCs in SCD. The analgesic properties of N2O are well known, and N2O is an FDA-designated medical gas that is used for its analgesic, among other, properties. Other potential disease targets are conditions associated with acute pain. About Hillhurst Hillhurst is a clinical stage company focused on its proprietary GLASS™ platform, which enables novel drug products based on therapeutic gases that, up until now, have been limited by inhaled delivery, including a unique pipeline of novel liquid therapeutic candidates intended to treat patients with acute pain, sickle cell disease, and Parkinson's disease. This research is supported by the NIH under grant number 1UG3NS127943-01, and its content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. To learn more about Hillhurst, please visit . View original content: SOURCE Hillhurst Biopharmaceuticals, Inc.