Potential Biohazards for Health Personnel Associated with Chronic Exposure to N₂O

Nitrous oxide/oxygen sedation has already been discussed as a safe procedure that does not pose health risks for patients. However, chronic exposure for health professionals administering the gas has been an issue of debate and concern for many years. No doubt research in this area will be ongoing; however, so will the advent of new equipment, materials, and practice controls. Minimizing waste gas will continue to be a priority for office personnel. This chapter outlines the best practices for management of occupational exposure to nitrous oxide.

1 History of Controversial Literature

A. In 1967, a scientist named Vaisman¹ reported that both male and female anesthesiologists in Russia experienced reproductive problems at a significantly higher rate than the general population. In addition, Vaisman concluded that these problems were caused by the occupational hazard of being chronically exposed to anesthetic gases. Because N₂O was a common denominator in most anesthetic applications, it was implicated as the causative agent.

B. In the United States, Cohen and colleagues^2–4 published articles in the 1970s dealing with anesthetic health hazards. One 1980 published study⁵ surveyed more than 50,000 dentists and dental assistants who were exposed to trace anesthetics. The results suggested that long-term exposure to anesthetic gases could be associated with an increase in general health problems and reproductive difficulty. In this study, ambient N₂O concentration in the office was not measured, and data were collected through memory recall by dental personnel.

C. Since Vaisman’s original article, the literature continued to document and describe potential adverse effects of chronic exposure to N₂O. Animal studies were conducted with the intent to impart relevant information to humans. However, much of the literature had design flaws. A majority of literature was primarily retrospective; therefore, inherent biases in study design were inevitable.⁶ Because of these flaws, a definitive relationship between the exposure of an individual to N₂O/O₂ and reproductive sequelae cannot be established.⁷ Weinberg and colleagues⁸ addressed these design flaws and proposed recommendations for future studies of this sort.

D. Also during the 1970s, Bruce and colleagues⁹ investigated the possibility of N₂O affecting perceptual cognition and psychomotor skills of personnel exposed to varying concentrations of the gas. Their results were widely noted, because they reported audiovisual impairment in just hours of exposure to as little as 50 parts per million (ppm). Multiple attempts to reproduce the research results of Bruce and colleagues have failed; interestingly, these researchers have retracted their conclusions, indicating the results were not based on biologic factors.¹⁰ The National Institute for Occupational Safety and Health (NIOSH) became interested in these and other results being published and in 1977 evaluated the scavenging potential of the equipment used in both the operating room and the outpatient setting. It was determined that 25 ppm was achievable in the operating room but not attainable in a setting such as a dental operatory. Therefore, NIOSH chose 50 ppm to be the maximum exposure limit for personnel in a dental setting.¹¹ Although this limit has not been strictly enforced by the Occupational Safety and Health Administration (OSHA), it remains the recommended standard to date.

E. Despite the negative publicity N₂O received, other studies in the literature claimed no deleterious health effects associated with chronic exposure to N₂O, especially in low concentrations.^12–16 The controversy continued in the literature and was the subject at professional meetings. Both sides of the issue were published; however, because the effects were questionable, the popularity of N₂O/O₂ sedation waned.

F. It became the work of this author to objectively and scientifically evaluate all the published research to verify the possible relationship of chronic exposure to N₂O and its subsequent effects on human health.

1. In 1995 a worldwide literature search on the topic of biohazards associated with N₂O use was conducted at the University of Colorado. A total of 850 citations were retrieved, of which 23 met the predetermined criteria for scientific merit.

2. The conclusions drawn from this literature review clearly indicated that there was no scientific basis for the previously established threshold levels for the hospital operating room or the dental setting.

3. This research became the basis for a meeting of interested parties representing dentistry, government, and manufacturing. A result of the September 1995 meeting, which was sponsored by the ADA’s Council on Scientific Affairs and Council on Dental Practice, was the formal position statement that a maximum N₂O exposure limit in parts per million has not been determined.¹⁵ A subsequent report from this meeting indicates that the ADA urges governmental agencies to create new recommendations or regulations dealing with N₂O exposure that are science-based.

G. Research and investigation on the subject of exposure to nitrous oxide gas will continue. It is important to note that work settings and safety practices for all professions have changed dramatically since the first implication of health concerns. Recommendations for air exchanges and air sampling were implemented in the operating rooms, while scavenging systems, personal monitoring, practice controls, and equipment upgrades have been instituted.⁷ Every attempt to minimize trace gas should be employed with attention given to the literature and industry when new products and best practices are recommended based on sound evidence.

2 Specific Biologic Issues and Health Concerns

A. Nitrous oxide oxidizes the cobalt(I) form of cobalamin (vitamin B₁₂), which then prevents cobalamin from acting as a coenzyme for methionine synthase. Methionine synthase is vital for the synthesis of several materials and functions, most importantly of which is DNA production and subsequent cellular reproduction. Inactivation of methionine synthase has been previously mentioned in Chapter 9, and will be mentioned again in subsequent chapters.

1. Inactivation of methionine synthase occurs rapidly in rats; exposure to 80% N₂O for only 15 minutes revealed inactivation of the enzyme.¹⁶ Because of this interference, it was postulated that fetal development might be impaired because of exposure to N₂O. Animal studies that used approximately 60% N₂O for 24 hours on pregnant rats produced miscarriage and other fetal abnormalities.¹⁷

2. The connection between nitrous oxide exposure and biohazardous effects has been documented.^18,19 Research has linked chronic exposure to high levels of N₂O with effects on DNA production and reproduction.⁵ However, there is still no evidence to date that a direct causal relationship exists between reproductive health and scavenged low levels of N₂O.^14,16,20

3. Because of the significant demands for folic acid during organogenesis (first trimester), postponement of N₂O sedation is recommended. For a pregnant female employed in a setting that uses N₂O, it is important to know the exposure levels of N₂O and to use all recommended trace gas scavenging methods. Depending on the individual and the situation, that employee should determine whether she should avoid the office setting and any N₂O exposure for the first trimester.

4. The deoxyuridine suppression test is a sensitive test used to accurately determine the first signs of biologic effect associated with chronic exposure to N₂O. The test detects the early signs of inactivation of the enzyme methionine synthase. By use of this test, Nunn and colleagues²¹ found that no alteration of this enzyme occurred in anesthetists exposed to between 150 and 400 ppm.

5. In their research, Sweeney and colleagues²² showed that the first sign of biologic effect with the deoxyuridine suppression test was at a chronic exposure level of 1800 ppm. Experts in the field concur that the level of 400 ppm, suggested by Sweeney and colleagues, is a reasonable exposure level that is both attainable and significantly below the biologic threshold established by Sweeney and colleagues. The Health and Safety Executive in the United Kingdom (HSE UK) Occupation Exposure Limits set a figure of 100 ppm as a time-weighted average for 8 hours.²³ Other country’s exposure limits range from 25 to 100 ppm with short-term peaks up to 500 ppm. The National Institute for Occupational Safety and Health has set the exposure limit for operating rooms within the United States to 25 ppm, with dental offices set at 50 ppm. See Box 16-1 for exposure limits in varying countries.

B. Suppression of methionine synthase activity has been shown to occur in some humans within 1 to 2 hours following the administration of 70% nitrous oxide.²⁴

1. Patients known to be cobalamin (vitamin B₁₂) deficient may deserve special attention with regard to nitrous oxide/oxygen administration.²⁰ Individuals with nutritional disorders or malabsorption issues may be sensitive to methionine synthase suppression. Such patients may include the elderly, alcoholics, those with modified diets or who have gastrointestinal problems or surgeries, or those with pernicious anemia.²⁰

2. Medical consultation and/or vitamin B₁₂ testing could be advised for individuals who are unaware of their status. Enzymatic activity has been shown to resume to normal levels within a few days.²⁴ However, in certain cases, vitamin B preoperative therapy may be advised before nitrous oxide/oxygen administration.

3. Sanders reports in Anesthesiology that there is “no evidence that individuals who are not deficient in cobalamin or folate are vulnerable to hematologic complications of nitrous oxide if exposed for less than 6 hours.”²⁰

C. Megaloblastic anemia, first described in the 1950s, was found in patients treated with N₂O for tetanus.²⁵ Leukopenia and reduced megaloblastic erythropoiesis resembling pernicious anemia ensued. Discussions continue regarding the toxicity of nitrous oxide and its effects on the body.^26–33 It continues to seem that nitrous oxide is safe when administered in low therapeutic doses for short periods of time.

D. Neurologic disorders associated with chronic N₂O exposure appear as myeloneuropathy.

1. Again, in cobalamin-deficient individuals, significant myelin degeneration has been reported.³⁴

2. Nitrous oxide abusers may endure symptoms such as sensory and proprioception impairment. These symptoms may be permanent but are usually temporary with slow recovery. If an abuser is also cobalamin-deficient, postoperative cobalamin/folate therapy may be required.²⁰

3 Scavenging Trace Nitrous Oxide Gas

A. Articles published in the 1990s refer primarily to scavenged versus unscavenged N₂O levels. In the 1990s, practitioners were educated on ways to effectively scavenge trace gas contamination, with the primary method being the evacuation system and the scavenging nasal hood or mask. Scavenging protocols are well established in current practice.

B. Scavenging N₂O means minimizing trace amounts of the gas before, during, or after use by the patient.

C. The term scavenging system traditionally referred to the mask and suction capabilities of the equipment but is currently a term used to identify several methods for the comprehensive removal of trace N₂O.

D. The scavenging mask system has become standard on all product lines in the United States. When expired N₂O is exhaled through the nose, vacuum suction ports transport this gas through the central suction to the outside atmosphere (Figure 16-1). Studies evaluating the scavenging efficacy of masks indicate that current models significantly reduce the amount of trace N₂O in the ambient air.^35–38

1. This evacuation flow rate has been established by NIOSH as optimal at 45 L/min.

2. Improved mask designs and/or evacuation devices are being investigated as modifications or additions to the current market.^36,39–43 As technology advances rapidly, no doubt there will be more efficient products. Ongoing research in this area is encouraged.

E. The published literature has served as a vehicle for informing healthcare professionals of the necessity to analyze N₂O exposure levels in their settings and the ways to minimize trace gas. However, there is evidence that some professionals practice without scavenging equipment and without the use of any other suggested recommendations.^44–46 The use of equipment that does not have scavenging capabilities is clearly a breach of the standard of care.

F. Research continues to surface in the literature regarding the occupational exposure of healthcare practitioners to nitrous oxide. Professionals are taking heed to follow recommended practice protocols and monitor personal exposure. Many articles cite the effectiveness of methods to scavenge trace gas, noting dramatic decreases in ppm of N₂O in ambient air.^47–57

4 Detection and Monitoring of N₂O in Ambient Air

A. Infrared (IR) Spectrophotometry

1. IR sp/>

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