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It has been 180 years since Horace Wells, assisted by Gardner Quincy Colton and John Mankey Riggs, successfully employed nitrous oxide as an anesthetic, demonstrating insensitivity to pain in a patient undergoing a dental extraction.1 Since then, nitrous oxide-oxygen sedation has become the standard of care for in-office inhalational sedation and is often regarded as the safest method dentists can use to help fearful and anxious patients relax.2 In fact, no reported death during a dental procedure in a dental office has ever been caused by nitrous oxide-oxygen sedation when used as the sole sedative and administered by means of a correctly installed and maintained delivery system.3
At present, 41 of 51 dental boards in the United States do not require additional postgraduate training beyond dental school or a specific permit for the use of nitrous oxide-oxygen sedation, and in medicine it is often used for self-administered analgesia by patients with cancer and during labor and delivery.4 Furthermore, nitrous oxide-oxygen is commonly used as preemptive analgesia and to alleviate pain and discomfort associated with various medical procedures, including peripheral intravenous cannulation, colonoscopy, sigmoidoscopy, intra-articular drug injection, ophthalmologic procedures, and biopsy procedures.5-10 In Europe, a 50:50 mixture of nitrous oxide and oxygen (commonly referred to by one of its trade names, Entonox®) is widely used during ambulance transportation in the emergency medical care of patients and at accident scenes.11-14
Safety Concerns
The episodic exposure of patients to nitrous oxide-oxygen has demonstrated a wide margin of safety. The largest randomized controlled clinical trial on this subject, the ENIGMA II trial, confirmed the safety of nitrous oxide-oxygen sedation, concluding, "There is therefore no reason to omit nitrous oxide from contemporary anaesthetic practice on the basis of concern about [death and cardiovascular complications] alone."15 The US Food and Drug Administration previously assigned a category C risk for pregnant patients' exposure to nitrous oxide-oxygen, and although this has been updated to the new Pregnancy and Lactation Labeling Rule, the information on nitrous oxide-oxygen remains the same: that adequate, well-controlled human studies are lacking; animal studies have shown a risk of adverse effects on the fetus; and there is a chance of fetal harm if administered during pregnancy, but the potential benefits may outweigh the potential risks.16,17 Although not shown to be a teratogen to the fetus following brief exposure, nitrous oxide depresses the activity of methionine synthetase, an essential enzyme for DNA synthesis, which could lead to a lack of biologically active folates essential to fetal development.18,19 It is therefore recommended to avoid the use of nitrous oxide for pregnant patients in their first trimester or those with methylenetetrahydrofolate reductase (MTHFR) deficiency.18,20
Despite the large inherent margin of safety with nitrous oxide-oxygen administration, staff concerns about potential harm from environmental exposure over time have led to the development of at least 12 safety features to mitigate occupational exposure (Table 1).3 When administered appropriately, by means of properly maintained equipment, nitrous oxide-oxygen sedation is a safe and easy technique to provide analgesia and anxiolysis in the dental office.
Concerns about climate change and global warming have recently renewed interest in the safety of nitrous oxide-oxygen administration, since many inhalational anesthetic agents are potent greenhouse gases.21 The extent to which global surface temperatures are increased by the atmospheric release of a particular greenhouse gas is referred to as its global warming potential (GWP). The GWP is determined by the contribution of a substance to global warming over a specified timeframe (usually 100 years; GWP100) referenced to an equivalent mass of carbon dioxide (CO2). This provides a foundation for greenhouse gases to be explained in terms of CO2 equivalents. For example, the GWP100 of desflurane is 2540, and the GWP100 of sevoflurane is 144, while that of nitrous oxide is 273.21-24 This means that nitrous oxide has a global warming potential 273 times that of CO2 over a 100-year timescale.24 In addition to its global warming effect, nitrous oxide can rise to the stratosphere where it can remain stable for more than 100 years, contributing to destruction of the ozone layer.18,25
This article reviews a new method to further reduce the exposure of office staff to ambient levels of nitrous oxide. It also reviews the risk of occupational exposure to nitrous oxide and mitigation of the environmental impact of the gases via a technique known as "cracking."
Occupational Exposure to Nitrous Oxide
The National Institute for Occupational Safety and Health (NIOSH) has demonstrated that controls-such as proper system maintenance, appropriate ventilation, and good work practices-can effectively reduce nitrous oxide concentrations in dental operatories to below the recommended exposure limit of 25 ppm (ie, 45 mg/m3) during analgesia administration.26 Adopting appropriate work practices and following the recommendations from the American Dental Association's Council on Scientific Affairs (CSA) and the Council on Dental Practice (CDP) can help dental offices safely employ nitrous oxide-oxygen while minimizing the potential exposure for office staff and environmental impact.27,28Some CSA/CDP best practices are listed in Table 2.27
Although current NIOSH recommendations set a safe level of nitrous oxide concentrations in dental operatories below 25 ppm, Sweeney et al first demonstrated in 1985 that occupational exposure must be kept below 1,000 ppm to prevent depression of vitamin B12 activity.29 Based on their findings, however, the final published recommendation was to keep ambient levels of nitrous oxide below 400 ppm in order to increase the safety factor at least twofold.29 Six years later, Yagiela asserted that, if 400 ppm per nitrous oxide administration is a reasonable exposure level, "a time-weighted average of 100 ppm for an 8-hour workday and/or a time-weighted average of 400 ppm per anesthetic administration would provide adequate protection of dental personnel…."30 The American Conference of Governmental Industrial Hygienists recommended a threshold limit value of 50 ppm, which introduced another doubling of the safety factor, and the current NIOSH recommendation of 25 ppm doubles this safety factor yet again.26,31
The ability to control occupational exposure to nitrous oxide in the dental operatory is achieved with a functioning scavenging system as well as the other safeguards described in the CSA/CDP recommendations.27,28,31,32 Scavenging systems use a combination of vacuum pumps and venting mechanisms to capture exhaled nitrous oxide and carbon dioxide from patients.32,33These systems then direct the captured gases safely out of the treatment area, usually venting them outside the building through dedicated exhaust systems. The overall dilutional effect of releasing waste gases such as nitrous oxide and carbon dioxide back into the atmosphere is shifting the discussion from patient and staff safety to environmental safety, given the high GWP100 of nitrous oxide, its global warming effect, and its destructive impact on the ozone layer.21,24,25
The current recommendations developed by the CSA/CDP draw attention to multiple sources of potential leaks within a nitrous oxide-oxygen sedation system.28 These include leaks at the manifold outlets and connections within the piping system, pendant connections in the dental operatory, flawed equipment design, and wasteful clinical practice, among others. In addition, there has been a recent resurgence of recreational use of nitrous oxide, and inadequate cylinder security can result in theft from dental offices.19,20 Following suggested best practices helps to minimize occupational exposure while ensuring that waste gases are scavenged away appropriately. Rather than releasing these waste gases into the atmosphere, however, there may be a new solution to mitigate nitrous oxide occupational exposure and emissions; this process is known as catalytic cracking, whereby exhaled nitrous oxide is converted into oxygen and nitrogen using a heated catalyst.
Catalytic Cracking for Nitrous Oxide Safety
The first use of commercial catalytic cracking was in 1915 by Almer M. McAfee at the Gulf Refining Company.34 Catalytic cracking is generally defined as, "the thermochemical reaction at the conditions of a hydrogen atmosphere, high pressure, and above 350°C under the catalytic action of catalysts."35 In the case of nitrous oxide, the catalytic process breaks down the gas at high reaction temperatures into oxygen and nitrogen, and, after cooling, these gases are released into the atmosphere.36
Two bench test experiments were recently completed with the aim of establishing whether catalytic cracking technology of scavenged nitrous oxide was effective under ideal circumstances and whether it would be reliable in clinical practice for continuously monitoring nitrous oxide levels.37 The first experiment used a nitrous oxide cracking device (Mobile Destruction Unit [MDU], Medclair) and a nitrous oxide-oxygen scavenging system (Ultraflow™, BPR Medical Gas Control), and the investigators showed almost 100% reduction in ambient nitrous oxide concentrations as the scavenged gas was safely converted to oxygen and nitrogen compared to the control arm. This result was consistent with the cracking device's manufacturer data, which state that more than 99% of nitrous oxide is broken down with this chairside catalytic cracking technology.38 The second bench test confirmed that this device would also be reliable in clinical practice for continuously and accurately monitoring ambient nitrous oxide levels.37
Based on these original experiments, Pinder et al undertook an exploratory, multisite investigation at three large hospitals in which nitrous oxide-oxygen was routinely provided as an analgesic during labor and delivery.39 A 50:50 mixture of nitrous oxide-oxygen was provided to patients for self-administration utilizing a number of different mask types, with the same MDU model employed by Gaines et al.37 The real-world data showed a reduction in ambient nitrous oxide levels between 71% and 81% in these obstetric settings. The authors concluded that the introduction of nitrous oxide cracking technology has the potential to reduce ambient levels of nitrous oxide, with positive implications for both occupational exposure and environmental impacts.39
Given the results from these trials, a recent editorial in Anaesthesia described climate change as a real crisis that is the social and moral responsibility of healthcare providers to mitigate by reducing the negative environmental impacts of healthcare to the best of their ability.40 While there is no ideal substitute for nitrous oxide, these data provide a helpful template that could support the implementation of nitrous oxide scavenging and cracking, rather than the current strategy of using scavenging alone.
Conclusion
Ensuring the continued safety of nitrous oxide-oxygen inhalational sedation for patients while reducing the environmental impact and exposure of office staff to ambient levels of nitrous oxide continues to be a priority. Recently, climate change and global warming have renewed interest in the safety of nitrous oxide-oxygen administration, because many inhalational anesthetic agents such as nitrous oxide are potent greenhouse gases. A new method known as cracking has been introduced that can further mitigate the emission of nitrous oxide as a greenhouse gas by converting scavenged exhaled nitrous oxide into oxygen and nitrogen, using a heated catalyst. While this emerging technology has so far been used in medicine, and although additional studies are certainly warranted, recent data suggest that the benefit and ease of operationalization of this new technology may support its use in dentistry in the future.
About the Authors
Mark Donaldson, BSP, ACPR, PharmD
Associate Principal, Kaufman Hall, a Vizient company, Irving, Texas; Clinical Professor, School of Pharmacy, University of Montana, Missoula, Montana; Clinical Assistant Professor, School of Dentistry, Oregon Health & Sciences University, Portland, Oregon; Adjunct Professor, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia; Fellow, American Society of Health-System Pharmacists; Fellow, American College of Healthcare Executives®
Jason H. Goodchild, DMD
Vice President of Clinical Affairs, Premier Dental Products Co., Plymouth Meeting, Pennsylvania; Associate Clinical Professor, Department of Oral and Maxillofacial Surgery, Creighton University School of Dentistry, Omaha, Nebraska; Adjunct Assistant Professor, Division of Oral Diagnosis, Department of Diagnostic Sciences, Rutgers School of Dental Medicine, New Brunswick, New Jersey
Queries to the author regarding this course may be submitted to authorqueries@conexiant.com.
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