Desflurane Should Des-appear: Global and Financial Rationale
Matthew J. Meyer
Abstract
Desflurane is a volatile anesthetic agent used throughout the world. Since 2001, global emissions of desflurane have increased from 150 tons per year to 960 tons per year in 20141 and this trend is expected to continue. The global market for desflurane was $244 million in 2018 and projected to increase by 5.1% each year through 2026.2 Anesthesiologists and anesthetists have an opportunity to improve our environmental impact on our world and our financial cost on our health systems. One singular choice, that can be made today, can do both. We need to stop using desflurane as a routine option for general anesthesia. There is no good reason to use desflurane in most patients, and there are a few great reasons to avoid desflurane altogether. Foremost, desflurane is a potent greenhouse gas and this contributes to climate change.3 Second, desflurane is more expensive than other volatile anesthetics.4 DESFLURANE’S HISTORY Desflurane became commercially available in the early 1990s. Desflurane’s low blood–gas partition coefficient offered hope for rapid inhalational inductions and quicker recoveries. An introductory Anesthesiology editorial,5 written by the then editor-in-chief Dr Lawrence Saidman, tempered expectations for desflurane with the statement “…it is too soon either to embrace desflurane enthusiastically or to suggest that its differences are insufficient enough to preclude wide spread [sic] use.” In pediatric anesthesiology, the potential for a rapid inhalational induction was meaningful. Unfortunately, desflurane was found to be a major airway irritant in the pediatric population with an early study documenting high incidences of breath-holding (50%), coughing (36%), and laryngospasm (30%).6 Over the last few decades, desflurane has been examined repeatedly in different patient populations and with different comparators to assess its impact on recovery from anesthesia. The results have been unconvincing. One recent meta-analysis collated randomized controlled trials in bariatric surgery—a population that should be ideal to demonstrate the theorectical benefits of desflurane’s pharmacokinetics and pharmacodynamics. This study documented that bariatric patients exposed to desflurane open their eyes to command faster (3.80 minutes; 95% confidence interval [CI], 1.83–5.76), extubate faster (4.97 minutes; 95% CI, 1.34–8.59), and have a slightly better initial postanesthesia care unit Aldrete score (+0.52 points; 95% CI, 0.19–0.84) when compared to patients exposed to sevoflurane.7 While these findings are statistically significant, with the exception of operating rooms (ORs) with workloads exceeding the typically allocated OR schedule,8 these findings may not be financially compelling. An attempt has also been made to link desflurane with improved postoperative cognition with the theoretically sound hypothesis that less soluble volatile anesthetics may have less impact on neurocognition. However, a meta-analysis published in 2015 noted, while desflurane does result in a faster time to following commands (3.27 minutes; 95% CI, 1.59–4.95) than sevoflurane, there is no difference in the incidence of postoperative cognitive dysfunction.9 Interestingly, a recently published retrospective study analyzing volatile anesthetics found a higher incidence of postoperative delirium in patients who received desflurane than those who received isoflurane.10 While it is far from certain that desflurane is associated with worse postoperative cognition, it is equally uncertain that desflurane is associated with improved postoperative cognition. When some scientists were searching for the advantages of desflurane, others were documenting its deficits: (1) desflurane is expensive, this was5 and continues to be4 true; and (2) desflurane is the most potent greenhouse gas of the modern volatile anesthetics by an order of magnitude.3,11 HEALTH CARE AND THE GLOBAL CLIMATE The World Health Organization has declared climate change “the greatest threat to global health.”12 Globally, health care is responsible for 4.6% of greenhouse gas emissions.13 In the United States, health care is responsible for 10% of US greenhouse gas emissions.14 Each year health care pollutants result in the loss of >400,000 disability-adjusted life years in the United States alone.14 This staggering number is similar in magnitude to the harm caused by medical errors reported in the groundbreaking Institute of Medicine article on patient safety15 that meaningfully changed the practice of medicine. It is time we acknowledge the harmful effects of health care on the environment and global health and act similarly. We must mitigate the impact of health care on the environment and consequently improve the health of everyone. As anesthesiologists we use volatile anesthetics every day, and, once the patient exhales, the gases are vented into the atmosphere. All volatile anesthetics are greenhouse gases, but some are worse greenhouse gases than others. The “20-year global warming potential (GWP20)” is a standardized unit used to compare the impact various molecules may have on the climate: a higher number means more potential to capture energy and thus greater impact on the climate. Carbon dioxide is the benchmark and has a GWP20 value of 1. Sevoflurane has a GWP20 of 349, isoflurane has a GWP20 of 1401, and desflurane has a GWP20 of 3714. When comparing minimum alveolar content per hour (MAC-hour) of anesthesia, desflurane at 1 L of fresh gas flow is 13 times worse than sevoflurane at 2 L of fresh gas flow.3 As anesthesiologists, we can begin with eliminating (or drastically reducing) desflurane venting into the air and have an impact on health care’s contribution to climate change immediately. DESFLURANE’S OUTSIZED POLLUTION PROFILE Large hospitals are approximately 2% of US commercial floor space but consume 4.3% of all energy delivered to the commercial sector.16 Operating suites with multiple cycles of conditioned air per hour, bright lighting, and complex electrical machinery are high consumers of energy. A recent study examined the impact of ORs on greenhouse gas emissions. Interestingly, in hospitals that used a disproportionate amount of desflurane (1 in Canada and 1 in the United States), anesthetic gases were responsible for over 50% of the greenhouse gas equivalents created in the OR; in the institution that did not use desflurane, anesthetic gas contributed only 4% (nitrous oxide use was negligible at all 3 of these institutions).17 For clarification, while the desflurane vaporizer is unique among volatile anesthesia vaporizers in requiring electricity, the amount of electrical energy is minimal.18 The actual desflurane molecules released into the atmosphere are responsible for the vast majority of greenhouse gas emissions attributable to desflurane usage. The overall contribution of anesthetic gases to total health care greenhouse gas burden has been estimated at 2% in England’s National Health Service (NHS). To contextualize this number, the NHS Sustainable Development Unit estimates a single hour of anesthesia; using the most carbon-intensive volatile anesthetic (eg, desflurane) is similar to the emissions from driving 370 km in a gas-powered automobile.19 By abstaining from (or dramatically reducing) desflurane, anesthesiologists can make a large reduction in these emissions with likely no clinical implications. DESFLURANE’S EXPENSE TO A HEALTH CARE SYSTEM A MAC-hour of desflurane has been calculated to cost $12.96 when used at 1 L of fresh gas flow; this is 2 times more expensive than sevoflurane (at 1 L of fresh gas flow) and 25 times more expensive than isoflurane (at 1 L of fresh gas flow).4 A recent study from Hungary calculated an hour of sevoflurane anesthesia to be (including all disposables and other pharmaceuticals) to be €12.15 ± 5.32 and an hour of propofol anesthesia (including all disposables and other pharmaceuticals) to be €13.23 ± 4.23.20 Extrapolating the cost per MAC-hour ratio of the different anesthesia choices, it is likely a MAC-hour of desflurane is generally more expensive than a MAC-hour of propofol (disposables included). Reducing or eliminating desflurane brings a financial benefit to institutions. Wake Forest Baptist Health (Winston-Salem, NC) educated its anesthesiologists, anesthetists, and trainees about volatile anesthetics and emphasized the appropriateness of isoflurane in many scenarios. By shifting away from more expensive agents (eg, desflurane), they have calculated over $1.8 million in savings, or approximately $1000 per day.21 Similar results were found at the University of Wisconsin (Madison, WI) where they estimate saving $25,000 per month.22 ARE THERE APPLICATIONS FOR DESFLURANE IN OPERATING ROOM ANESTHESIA? The coronavirus disease 2019 (COVID-19) pandemic may provide a setting for desflurane to be used. In hospitals where conservation of personal protective equipment (PPE) is paramount, patients may go through phase 1 of anesthesia recovery in the OR to reduce consumption of PPE by recovery room staff and risk of contamination of recovery room staff and the physical plant.23 In this situation, the potential OR efficiency gained using desflurane over other inhaled anesthetics24 may result in more cases performed during scheduled OR hours while reducing PPE consumption and risk of transmission to staff and other patients. The novelty and complexity of this situation warrants additional analysis especially considering the relationship between desflurane and coughing25 and thus the aerosolization of respiratory secretions. There are many different systems of OR anesthesia throughout the world. Undeniably, there are instances where the pharmacodynamics of desflurane could improve the focused definition of OR efficiency (surgery per unit time). In general, these situations involve individual ORs where the final procedure (or procedures) could be performed inside of a scheduled workday8 if the occurrence of prolonged extubation time (>15 minutes) could be reduced.26 Meta-analyses comparing desflurane to isoflurane24 and sevoflurane27 found that desflurane was associated with markedly fewer prolonged extubations. Desflurane may also be of unique value in hospitals without recovery rooms, such as in many hospitals in Japan.28Figure 1.: Global social cost of volatile anesthesia choice. The global social cost (expected economic damage) of carbon dioxide has recently been estimated at a median of $417 per ton. A, The social cost of anesthetic emissions is calculated for different volatile agents and different FGF. B, The social cost of anesthetic emissions is normalized to the option with the lowest social cost per MAC-hour (isoflurane at half a liter of FGF). Notably, data for sevoflurane were only available for 2 L of FGF and not for lower flows. CDE 20 indicates carbon dioxide equivalents over 20 y; FGF, fresh gas flow; MAC-hour, minimum alveolar content per hour (measure of anesthesia that 50% of patients will not respond to surgical stimulus).However, while all of these instances may improve OR efficiency, we must balance the importance of OR efficiency against broader societal goals. The social cost (expected economic damage) of greenhouse gas emissions29 associated with anesthetic choice3 may be 12 times more (or greater depending on fresh gas flow) for desflurane than for isoflurane (see Figure 1). Considering this negative externality alongside of the calculation of OR efficiency may make desflurane less economical in many of these situations. ELIMINATING DESFLURANE Remove It One way to ensure desflurane usage is reduced is to eliminate the vaporizers. This can be accomplished by leadership or grassroots support from a majority of a department or practice. Simply removing vaporizers streamlines the OR because it will be an entire set of vaporizers that no longer need to be maintained and an entire drug that no longer needs to be purchased and stocked. However, this approach may not be popular because individual clinicians may recoil if they believe financial policy is limiting their clinical practice. Educate on It Wake Forest demonstrated the efficacy of focused education encouraging usage of a volatile anesthetic besides desflurane. While they published data related to the financial impact,21 it is likely that the impact on greenhouse gases is as impressive. Education should be directed toward the values of the audience. Depending on your colleagues, education can focus on environmental stewardship, clinical appropriateness, or financial savings—because all 3 of these approaches are valid and can motivate different clinicians. Meaningful Change The elimination of desflurane is a large step toward improving the greenhouse gas footprint of an OR. However, there are a few other behaviors that must be discussed to ensure the change is not counterproductive (Figure 2). First, nitrous oxide must not be substituted for a quick-acting anesthetic gas. Along with desflurane, nitrous oxide is a bad greenhouse gas—its GWP20 is 289 and this underestimates its impact significantly because it will exist in the atmosphere for 114 years.3 A single hour’s application of 50% nitrous oxide with 50% air at only 1 L of fresh gas flow may create equivalent greenhouse gas emissions as driving an automobile 120 km—there are some who argue nitrous oxide has a larger impact on anesthetic-related greenhouse gas creation than desflurane.30 From the perspective of climate change, nitrous oxide should be avoided unless clinically imperative.Figure 2.: Reducing the global/financial costs of general anesthesia. Here are a few simple maneuvers an anesthesiologist can do to reduce the cost of his/her work on departmental finances and global environmental health. GHG indicates greenhouse gas; GWP20, global warming potential over 20 y; MAC-hour, minimum alveolar content per hour (measure of anesthesia that 50% of patients will not respond to surgical stimulus).Second, low-flow anesthesia should be practiced; all volatile anesthetics should be delivered with the minimum, clinically appropriate fresh gas flow. Historically, the US Food and Drug Administration’s recommendation of at least 2 L of fresh gas flow for sevoflurane anesthesia (concern related to compound A) has been a barrier to the adoption of low-flow anesthesia techniques in the United States. However, the Chair of the Committee on Technology at the Anesthesia Patient Safety Foundation published “Based upon the literature, we believe that our recommendation to use absorbents without KOH and low concentrations of NaOH is sound, and supports the safe use of low-flow or closed-circuit anesthesia in the presence of sevoflurane.”31 Hopefully, adoption of this carbon dioxide absorbent technology along with said guidance from the Anesthesia Patient Safety Foundation will accelerate the adoption of this important practice in the United States. Extrapolating from earlier research,3 low-flow sevoflurane anesthesia has the least greenhouse gas impact of any volatile anesthetic. For particularly attentive anesthesia practitioners, closed-circuit technique can be performed that absolutely minimizes the amount of volatile anesthetic used and released into the environment by supplying only enough fresh gas to fulfill metabolic requirements.32 Dr Sherman’s group from Yale Health (New Haven, CT) took many of the aforementioned principles and developed a smart phone application called Yale Gassing Greener (https://publichealth.yale.edu/climate/research/conferences/challenge/) to assist in anesthesia planning. Clinicians enter the medications they plan on using, and the application calculates cost and greenhouse gas emissions. This is a phenomenal tool for anesthetists throughout the world interested in environmental and financial stewardship.Figure 3.: Organizations throughout the world engaged with OR efficiency and environmental sustainability. OR indicates operating room.Anesthesiology as a profession reaches into many aspects of the health care system beyond the OR. While outside the scope of this article, it is important to note that anesthesiologists can and should improve health care efficiency beyond anesthetic gases and fresh gas flows. Anesthesiologists can modify technology, consumable, and pharmacy choices by considering life cycle analyses; they can improve recycling and waste reduction efforts inside and outside the OR; and they can influence system-wide decisions related to energy—the limitation is creativity and motivation. Organizations throughout the world engaged with broader perioperative efficiency and environmental initiatives are listed in Figure 3. Why It Matters A counter argument to eliminating desflurane usage is that anesthetic gases are not a major greenhouse gas contributor and therefore not worth modifying. One estimate of the total greenhouse gas impact of anesthetic gases calculates anesthetic gases to have 0.01% that of fossil fuel consumption.33 While that is likely an underestimation of volatile anesthesia greenhouse gas impact, because the calculations come from an institution with limited desflurane usage,34 even if anesthetic gases are only the first of 10,000 steps needed to arrive at the solution, we will never reach our destination without taking that step. Stop Using Desflurane Many institutions have already decreased their usage of desflurane—for both financial reasons as at Wake Forest,21 and climate change concerns as at the University of Wisconsin.22 With limited desflurane usage, these institutions continue to provide anesthesia services for a wide range of patient acuity and surgical complexity. Almost all patients can undergo anesthesia without desflurane. There is multinational interest in decreasing the usage of desflurane.35,36 The NHS in the United Kingdom explicitly states “The NHS Long Term Plan aims for a 51% reduction in the NHS carbon footprint by 2025, with 2% of this to come through ‘transforming anaesthetic practices’ such as using alternatives to desflurane.”37 And the American Society of Anesthesiologists has a specific Inhaled Anesthetic Challenge 2020 with a focus on reducing desflurane usage.38 With health care’s emphasis on value-based care, considering what we know about desflurane’s financial and environmental costs, the onus is on the clinician39 to have evidence for improved outcomes for their patient when choosing desflurane. It is rare when a single clinical behavior can reduce either OR cost or environmental harm. Avoiding desflurane will do both. While eliminating desflurane will not alone solve the climate crisis, it is a step toward solving the climate crisis. Most importantly, it can be done today and does not need any advance in technology or implementation of government policy. Collectively as anesthesiologists, we can make an instantaneous reduction in greenhouse gases and have a positive impact on global health, by simply turning off the desflurane canister. ACKNOWLEDGMENTS I thank Dr Aaron Bernstein for planting the seed for this manuscript. I thank Drs Marcel Durieux and Jodi Sherman for reviewing initial manuscripts. I thank Dr Martin Vollmer for his atmospheric research on volatile anesthetics and his rapid response to my inquiry. I thank the clinician anesthesiologists (many cited in this article) who have led the way researching the global health implications of the practice of anesthesia. I thank my colleagues at the Department of Anesthesiology, University of Virginia, for their support in our effort to make our anesthesia practice more sustainable while maintaining excellent quality of care. DISCLOSURES Name: Matthew J. Meyer, MD. Contributions: This author helped design, research, write, and revise the manuscript. This manuscript was handled by: Ken B. Johnson, MD.