Potential Hazards and Best Practices Associate with Nitrous Oxide

Nitrous oxide (N2O) is a reliable inhalation anesthetic that provides effective sedation and analgesia, as well as being safe when used correctly. However, medical professionals who frequently administer it should be aware of the possibility of long-term exposure.

 

This article will examine the research and potential hazards of N2O, commonly known as laughing gas and the correlated use in dental settings.

 

Retrospective Studies

In 1967, Vaisman¹,  a Russian scientist reported that female and male anesthesiologists experienced reproductive issues at a much higher rate than the general population. Vaisman concluded these problems were caused by occupational hazards of being chronically exposed to anesthetic gases. Given that N2O was a common denominator in the anesthetic applications studied, it was implied as the causative agent.

 

In the 1970s and 80s, Ellis N. Cohen, MD, a Stanford University School of Medicine anesthesiologist whose research revolutionized how operating rooms are now designed, published articles² anesthetic health hazards.

 

One of Cohen's studies surveyed over 50,000 dentists and dental assistants exposed to trace anesthetics. The results suggested that long-term exposure to anesthetic gases could lead to general health problems and reproductive difficulty for those exposed to trace anesthetics. The results indicated that long-term exposure to anesthetic gases could be associated with an increase in general health problems and reproductive difficulty.

 

Although research studies have continued to reveal the potential harmful effects of chronic exposure to N2O, it is important to note that these studies have been retrospective. As a result, there may be biases in the study design that could affect the accuracy of the results. Due to these flaws, it cannot be definitively established whether there is a causal relationship between an individual's exposure to N2O/O2 and reproductive issues.

 

Dental Setting Exposure

The National Institute for Occupational Safety and Health (NIOSH) conducted an evaluation of the scavenging potential of equipment used in operating rooms and outpatient settings in 1977. They found that achieving 25 ppm of N2O was possible in the operating room, but not in a dental operatory.

 

As a result, NIOSH established a maximum exposure limit of 50 ppm for personnel in a dental setting. Although this limit has not been strictly enforced by the Occupational Safety and Health Administration (OSHA), it is still the recommended standard.

 

Despite the negative publicity N2O has received, other studies in the literature have claimed that there are no harmful health effects associated with chronic exposure to N2O, especially in low concentrations.

 

Further Evaluation Indicates Exposure Duration Factor

In 1995, the University of Colorado conducted a worldwide literature search on the topic of biohazards associated with N2O use. Their literature review indicated that there was no scientific basis for the previously established threshold levels for the hospital operating room or the dental setting. This led to a meeting of interested parties representing dentistry, government, and manufacturing, which resulted in a formal position statement stating that a maximum N2O exposure limit in parts per million has not been determined.

 

There is evidence that chronic exposure to high levels of N2O affects reproduction, but to date, no evidence has been found that a direct causal relationship exists between reproductive health and scavenged low levels of N2O.

 

Sweeney et al.³ conducted a study that showed the first indication of any biological effect from N2O was observed at a chronic exposure level of 1800 ppm. Experts agree that 400 ppm is a reasonable exposure level, which is significantly below the established biological threshold. (Sweeney et al.)

 

N2O interferes with the enzyme methionine synthase, which is responsible for recycling homocysteine back to methionine. Methionine synthase is crucial in the metabolic pathways of vitamin B12 and folic acid and in the production of DNA. Prolonged exposure to N2O can lead to megaloblastic hematopoiesis and leucopenia.

 

It was hypothesized that fetal development might be impaired due to this interference. In animal studies, pregnant rats exposed to approximately 60% N2O for 24 hours experienced miscarriage and other fetal abnormalities.

 

Chronic exposure to N2O can result in neurologic disorders such as myeloneuropathy. While symptoms such as sensory and proprioception impairment may be permanent, they are usually temporary with slow recovery.

 

Recommendations 

 

It’s recommended to postpone the use of N2O sedation during pregnancy due to the high demands for folic acid during organogenesis (first trimester) and the link between high levels of homocysteine and congenital disabilities. For pregnant women working in environments where N2O is used, it is important to know the levels of N2O exposure and to use all recommended trace gas scavenging methods. 

 

Depending on the individual and the situation, dental professionals should decide whether to avoid the office setting and any N2O exposure during the first trimester.

 

Discussions are ongoing regarding the safety of nitrous oxide. However, it appears that the gas is safe when administered in low therapeutic doses for short periods. To maintain safe levels of nitrous oxide in a dental office, there are several measures that can be taken. 

 

• A scavenging system can be used to redirect N2O outside of the office. This is the most effective method. A scavenging mask system has become standard on all product lines in the US and Canada. When expired N2O is exhaled through the nose, vacuum suction ports transport the gas through the central suction to the outside atmosphere. NIOSH has established that an evacuation flow rate of 45 L/min is optimal.
• Good ventilation in the operatory can dilute the concentration of the gas. 
• Well-fitting masks can reduce leakage. One of the newest advances in nitrous oxide administration is the Safe Sedate Nasal Hood. This apparatus provides more efficient delivery of gases into the nasal nares while reducing extraneous nitrous oxide into the operatory. The Safe Sedate Nasal Hoodis also latex-free and disposable, preventing cross-contamination.

• Reduced talking by the patient decreases the exhalation of nitrous oxide into the operatory environment. 
• Gas can leak at any place of connection on the equipment. This includes the manifold and wall-mounted connections and any hoses associated with each. Conducting tubing and the reservoir bag are also areas of concern. Because of the breakdown of these materials over time, these items can crack and subsequently leak around pleats and seams. 
• The soap and water method for determining leaks is recommended for inspecting these areas. The bubbles after applying the soapy water indicate a gas leak. 
• Various commercially available monitoring systems are capable of alerting dental staff to potentially unsafe N2O exposure levels. These systems include infrared (IR) spectrophotometry, time-weighted average (TWA) dosimetry, and hand-held monitoring devices.

 

In Conclusion

 

There is currently no direct evidence that shows chronic low-level exposure to N2O causes any biological effects. The maximum safe concentration of N2O isn’t fully understood, but measures should be taken to reduce the level of trace N2O that professionals are exposed to. Furthermore, it’s important for dental practitioners to be cautious when their health and coworkers' wellbeing are at stake.

 

Dental professionals who use N2O/O2 sedation should be required to continue their education, and they should have evidence of proper training with state-of-the-art equipment and N2O administration techniques.

 

1. Vaisman A: Working conditions in surgery and their effect on the health of anesthesiologists, Eksp Khir Anesterziol 3:44, 1967.
2. Cohen, E.N., Bellville, J.W. and Brown Jr., B. (1971) Anesthesia, Pregnancy, and Miscarriage: A Study of Operating Room Nurses and Anesthetists. Anesthesiology, 35, 343-347.

1. Vallejo MC, Zakowski MI. Pro-Con Debate: Nitrous Oxide for Labor Analgesia. Biomed Res Int. 2019 Aug 20;2019:4618798. doi: 10.1155/2019/4618798. PMID: 31531352; PMCID: PMC6720045.