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Nitrous Oxide and Oxygen Sedation—An Update

Ann Brunick, RDH, MS; and Morris S. Clark, DDS, FACD

July 2016 Course - Expires July 31st, 2019

American Dental Assistants Association


Nitrous oxide and oxygen (N2O/O2) in combination have been used safely and successfully for over 160 years to assist in the management of pain and anxiety. Dr. Horace Wells, a dentist in the early 1800s, dedicated his life to promoting its use for both dental and medical procedures. Because of his persistence in advocating the use of nitrous oxide as a method of pain control, he was posthumously recognized as the “Discoverer of Anesthesia.” Since that time, N2O/O2 has been commonly used in many dental specialties.
Other health disciplines have also benefited.
In many instances, patients present to medical and dental offices with both pain and anxiety. It is necessary to manage both, since they are interrelated. Nitrous oxide and oxygen sedation can assist patients with their pain and anxiety and can be employed safely and effectively with minimal concerns.
This course will teach about the desirable characteristics of nitrous oxide, indications and contraindications for N2O/O2 use as well as facts and myths surrounding chronic exposure to nitrous oxide, the biologic effects associated with high levels of the gas, and ways to assess and minimize trace gas contamination in an outpatient setting.

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ACGIH—American Conference of Governmental Industrial Hygienists

NIOSH—National Institute of Safety and Health

N2O/O2—Nitrous oxide and oxygen

OSHA—Occupational Safety and Health Administration

ppm/ppb—parts per million/parts per billion

TWA—time weighted average


anesthesiologist—a physician specializing in the administration of anesthetic

anxiety—a condition of heightened, often disruptive tension accompanied by a feeling of impending harm or injury

baseline values—a reference point used to indicate the initial condition against which future readings are compared

bleomycin sulfate—an anti neoplastic antibiotic

consent form—willing permission in a written format; allowing treatment

contraindication—a symptom that indicates against an otherwise normal form of treatment

COPD—Chronic Obstructive Pulmonary Disease, such as emphysema and chronic bronchitis

cystic fibrosis—an inherited disorder causing exocrine glands to produce abnormally thick secretions of saliva and an elevation of sweating

evidence-based evaluation—a philosophy that relies on up-to-date, current research to evaluate the patient’s condition and course of treatment

flowmeter—a physical device measuring the rate of flow of a gas

graft—a slip or portion of tissue used for reimplantation

hypersensitive—abnormally sensitive reaction when in contact with an allergen, bacteria, or stimuli

intracranial pressure—pressure occurring within the cranium due to head trauma, inflammation or infection

macular hole repair—to repair the partial or full absence of the retina in the macular area of the eye

methionine synthetase—one of the essential amino acids and essential for the production of DNA

nitrous oxide—gas with a sweet odor and taste used with oxygen as an analgesic and sedative agent

organogenesis—the formation of organs within an embryo, within the first trimester

parasthesia—altered sensation where the sensory nerve in question has been afflicted by injury or disease

pharmacological agents—drugs prescribed to treat patients

pneumoencephalography—radiography of fluid-containing structures of the brain after cerebrospinal fluid is intermittently withdrawn by lumbar puncture and replaced by a gas

pulmonary fibrosis—is the formation or development of excess fibrous connective tissue (fibrosis) in the lungs, described as “scarring of the lung”

psychological impairment—a mental state that disables a patient in some manner

reservoir bag—a part of the NO2/O2 machinery, contains the excess gas

scavenge—to collect and remove excess

sedation—producing a sedative effect, the act or process of calming

sinusitis—inflammation of the sinus

spectrophotometer—an infrared instrument used to report nitrous oxide levels

time-weight average device (TWA) - a dosimetry device containing a material that absorbs nitrous oxide, the badge or vial is returned for analysis

titrated—incremental increase of a drug to a level that provides optimum result

trace gas—any gas that represents an extremely small or insignificant portion of a mixture of gases

trimester—one third of a full pregnancy term

tympanic membrane—a thin, semi transparent membrane in the middle ear that transmits sound vibrations to the internal ear

unscavenged trace—escaped, harmful gas left in the air for the dental team

upper respiratory tract—the nose and throat and trachea, passages through which air enters and leaves the body


Nitrous oxide/oxygen (N2O/O2) sedation offers many advantages over other sedation methods or pharmacological agents. The properties of nitrous oxide allow it to provide pain relief while simultaneously reducing anxiety. This action happens within a short period of time. For example, bronchial asthma can be triggered by various stimuli, including stress. By employing the N2O/O2 sedation technique, basic appointment stressors can be minimized for a more comfortable experience.

The drug can be titrated, which means the patient is given incremental amounts over time until the desired level of sedation is achieved. This allows for the greatest level of patient comfort and safety. Elimination of nitrous oxide from the body occurs as rapidly as the induction. Patients are fully recovered following N2O/O2 sedation because all but an insignificant amount of drug is expelled from the lungs within minutes after the nitrous oxide is discontinued. These characteristics make it a desirable agent for practitioners.

In addition to these ideal characteristics, N2O/O2 sedation can be used on most patients with minimal side effects. Patients of any age can be given nitrous oxide and oxygen. In addition to relieving pain and anxiety, N2O/O2 sedation works very well at calming a hypersensitive gag reflex that can prohibit taking intraoral radiographs. There are very few contraindications for its use in the dental office setting because it does not negatively impact the majority of the body systems to any significant extent.


There are some situations in which the use of N2O/O2 sedation should be postponed or avoided. Whenever there is a question about whether N2O/O2 sedation should be used, it is always recommended to consult a physician. The following are conditions in which medical consultation is advised prior to nitrous oxide administration and/or nitrous oxide should be postponed until the condition is resolved, or not used at all.

The use of drugs during the first trimester of pregnancy is not recommended. Therefore, nitrous oxide during this period of organogenesis should not be used. Dental treatment is generally recommended to be completed during the second trimester. N2O/O2 sedation can be used during the second and third trimesters, although medical consultation with the patient’s physician is necessary.

Upper respiratory tract infections (i.e. sinusitis) typically result in nasal obstruction in which the gases cannot enter the respiratory system. This is a situation where N2O/O2 sedation is appropriate when the condition is resolved.

There are certain chronic obstructive pulmonary diseases (COPD) that pose problems with N2O/O2 sedation. If a patient indicates health problems associated with chronic bronchitis or emphysema, N2O/O2 sedation is a contraindication due to narrowed or enlarged airways that prevent proper inhalation or exhalation of the gases. Depending on the respiratory function of the patient, some cases are not problematic; therefore, medical consultation is essential for all patients with COPD.

Because of the expansive nature of nitrous oxide, there are several situations/conditions that warrant caution. The possibility exists in patients with active cystic fibrosis that complications could arise if nitrous oxide is used. Similarly, complications could occur in patients where a gas bubble was placed to assist healing during a recent eye surgery. This is typically surgery involving retina and macular hole repair.1 Also, patients who have recently undergone ear surgery to repair/replace the tympanic membrane with a graft could have complications from the use of nitrous oxide.2 Patients may get precautionary advice from their physicians about the use of nitrous oxide following these types of surgeries. Other potentially problematic situations related to gas expansion are pneumothorax (hole in the lung) and significant bowel impaction. However, it would be unlikely that a patient would present to a dental office with these conditions. Again, medical consultation is always prudent in such situations.

There is a potential to increase the incidence of pulmonary fibrosis and other pulmonary diseases in patients who are currently receiving bleomycin sulfate, which is a drug used to treat certain types of cancers.3 This situation is not related to the use of nitrous oxide, but rather the use of oxygen (greater than 30%) in combination with the nitrous oxide. This is an unlikely situation.

In addition, the literature cites notable intracranial pressure increases following recent pneumoencephalography procedures. In this case, nitrous oxide rapidly replaces the nitrogen resulting in an increase in pressure. N2O/O2 sedation should be postponed for one week after this procedure.4

Situations involving patients with psychologic impairment, mental illnesses or altered mental states require significant caution. N2O/O2 sedation should not be used when a patient is intoxicated or “high” on drugs. In addition, N2O/O2 sedation should not be used if a patient is unable to understand the procedure because of a mind-altering condition (ie, Alzheimer’s disease). And, if a person has a condition in which psychotropic drugs are prescribed, N2O/O2 sedation should be avoided. It is always best to obtain medical consultation whenever there is a question about a specific situation. Remember, there are other modes of sedation that are available for use in these instances.

If a patient won’t sign a consent form for N2O/O2 sedation, or is unwilling to receive it, you should not begin the procedure. You should also refrain from using N2O/O2 sedation with persons who can’t communicate with you because of a language barrier or those who have claustrophobic tendencies and are not able to wear the nasal mask and scavenger system.

There may in the future be other situations in which N2O/O2 sedation will be deemed inappropriate. It is vital for all healthcare providers to critically evaluate the latest research.


Evidence-based evaluation of the scientific literature is the necessary basis for sound practice. One of the areas in which the literature generally has not been scientifically validated deals with nitrous oxide as an occupational hazard. Unfortunately, there have been many references in scientific literature referring to nitrous oxide as a significant risk factor for healthcare professionals exposed to the gas during patient treatment. Historically, the literature has made reference to nitrous oxide as the causative agent for anything from birth defects to cancer. Validated research suggests that low levels of trace nitrous oxide in the workplace are safe, and great strides have been made regarding the efficacy of the equipment used and the ability to scavenge trace gas from the dental office. It is now possible to keep levels of trace gas to a minimum, thus reducing occupational risk.

Defining legitimate research often hinges on its design and methodology. From the more than 800 articles that have been written on the subject of nitrous oxide up to 1995, fewer than 25 were shown to merit reliability and validity.5 There have been many inconsistencies and inaccuracies presented in the literature regarding the harmful nature of nitrous oxide to those professionals who use it for patient treatment. Many of these studies were done using a retrospective survey design. This type of research lends itself to be unreliability because it is unable to control for extraneous factors.

The earliest study referring to nitrous oxide as a hazardous agent dates back to 1967. Nitrous oxide was cited by a Russian anesthesiologist as the cause of both male and female reproductive problems among anesthesiologists.6 Since nitrous oxide was a common gas used for operating procedures, it was singled out as the etiologic factor. Articles of a similar nature surfaced in the United States in the 1970s and early 80s, each claiming similar results. These studies quoted significant biologic effects when high levels of unscavenged, trace nitrous oxide were measured.

Since those early studies, methods of delivering and scavenging nitrous oxide have improved tremendously. It is now considered the standard of care to use equipment with scavenging capabilities. The equipment manufacturing industry has been instrumental in providing professionals with quality products and machines capable of scavenging much of the trace gas. Also, it is important to note that these manufacturers are continually improving the capabilities of their equipment. Research is ongoing at each manufacturing site; new products and methods are constantly being evaluated.

There is one reputable study that has determined the level at which true biologic effect occurred on humans following nitrous oxide exposure. In 1985, Sweeney et al used a sensitive measure, the deoxyuridine suppression test, to identify this critical level. His results showed the first signs of detectable biologic effect were found at 1800 parts per million (ppm).7 Noteworthy is the fact that, to date, no biologic effects have been evidenced when low levels of trace nitrous oxide gas have been measured.


The most significant biologic effect that has been linked to nitrous oxide exposure is its ability to inactivate Vitamin B12. This inactivation further affects an enzyme called methionine synthetase. Methionine synthetase is essential for the production of DNA. Abnormalities in fetal development were seen in animal fetuses that were exposed to 24 hours of 60% nitrous oxide for 12 days.8 Despite flawed research, reproductive problems with humans have been reported in individuals chronically exposed to high levels of unscavenged nitrous oxide.8 The issue of DNA interruption is important to those professionals early in pregnancy or trying to become pregnant. Knowing trace gas levels in the office would be beneficial in these cases. It is the individual’s decision whether to continue or postpone employment during this time. The toxicity of nitrous oxide and its effects on the human body remains a topic of discussion in the current literature.10-12 It is certainly recommended to keep updated on this topic; however, it continues to seem that nitrous oxide is safe when administered in low therapeutic doses for short periods of time.

Neurologic signs and symptoms are associated with nitrous oxide abuse. Individuals professing misuse of nitrous oxide experience numbness, tingling, and possibly parasthesia in their limbs. Impaired dexterity, clumsiness, and slowed gait are also signs. Reflexes may be impaired; muscles can weaken. The length of time and amount of exposure can influence these signs and symptoms. The cases of overexposure stated in the literature ranged from one to several hours per day and up to several times per week. Some individuals report gradual improvement of these symptoms upon termination of the abuse activity while others note permanent neural injury.13


The National Institute for Occupational Safety and Health (NIOSH) and the American Conference of Governmental Industrial Hygienists (ACGIH) were instrumental in establishing recommendations for threshold limits during administration and for an 8-hour time-weighted average. In 1977, these organizations established threshold limits for health professionals. It was established that a level of 25 ppm and 50 ppm must be achieved in operating rooms and dental offices respectively. These levels were based on unfounded research results later recanted by Bruce, Bach, and Arbit as well as the scavenging ability of the equipment at that time. Health professionals are required to uphold these arbitrary values even at the present time. The Occupational Health and Safety Administration (OSHA) is the organization that has the authority to enforce these recommended levels; however, because of the controversy regarding the appropriateness of the recommendations, OSHA recognizes that these limits must be validated.

In order to bring several issues up-to-date regarding nitrous oxide, a meeting was convened in October 1995 by the American Dental Association Council on Scientific Affairs. Several interested parties were represented including respected experts in the field, educators, manufacturers, and government officials. It was concluded that a true recommended exposure limit to nitrous oxide has not been established.14 Sweeney and colleagues have proposed a level of 400 ppm for regulatory consideration. They believe this level is attainable and well below the level (1800 ppm) at which they first detected biologic effect. Other countries have adopted exposure limits ranging from 25 ppm (France and Denmark) to 100 ppm (Sweden and Germany).


In order to determine whether trace nitrous oxide levels are significant in your facility, it is necessary to measure the levels in parts per million. An instrument called an infrared spectrophotometer is designed to instantaneously report nitrous oxide levels. Many other gases can be measured with this instrument as well. This technology can detect levels as low as parts per billion (ppb). It is not necessary to purchase this piece of equipment since periodic evaluation is all that is needed. It may be rented directly through a manufacturer or it is possible to consult a biomedical engineering agency through a local hospital or surgical center for available services. Also available is a small, lightweight, hand-held device that gives a continuous measure of nitrous oxide in room air. This machine can also detect gas leaks around equipment.

It is also possible to determine the amount of nitrous oxide exposure to an individual over a specified period of time. A personal monitoring device is worn similar to a radiation-dosimetry badge for the recommended period. The time-weighted average (TWA) dosimetry device contains a material that absorbs nitrous oxide. The badge or vial is returned to the supplier for analyzing. A written report is provided by the company indicating exposure levels for the specified period of time. These devices are inexpensive, easy to use, and readily available through a number of reputable companies. The hand-held unit aforementioned also has TWA measurement capabilities with immediate readout on the machine.


It is prudent to employ as many measures to reduce the amount of trace gas contamination in the office as possible.14 Scavenging nitrous oxide can occur before, during, and after patient use. Nitrous oxide can leak from several sources. Certainly, the equipment and its connections are a potential source of trace gas. Gas can leak at any place of connection on the equipment, whether the system is portable or centrally installed. The tanks themselves may leak at the valve stems. Gas can leak through any portion of a central piping system or through connections near the flowmeter. Manufacturers of nitrous oxide equipment suggest periodic evaluation and routine maintenance checks. Check with your manufacturer for the recommended time period; one company has suggested a maximum of two years. Conduction tubing and reservoir bags provide a potential source of trace gas. These items should be inspected frequently for cracks and tears. The soap/water test (instructions for this test are in the next section) is appropriate for testing these items. The evacuation system used to pull trace gas from the mask into the suction must be in good working order and have properly vented pumps. If equipment is used that is not able to pull trace gas into the evacuation system from the nasal hood, the professional is practicing below the standard of care set by the dental profession. This could lead to serious legal repercussions.

Another significant potential source of trace gas is from the patient. One of the most critical means for waste nitrous oxide invading the operator’s breathing space is through patient talking. It is imperative to keep patient talking to an absolute minimum during administration. It is also possible for gas to escape into the room from the patient’s mask. Considerable effort should be made to ensure a properly fitting mask. There are many varieties of masks and a range of sizes. Appropriate flow will not force gas out the sides of the mask. Sometimes, all that is needed to create a snug fit around the patient’s nose is a slight twist of the conduction tubing on the mask. A physical property of nitrous oxide is that it is heavier than nitrogen (air). While it may seem logical to think that because of this property, the gas would immediately fall to the floor and pose no risk to the operator(s), one must not forget that the gas is extremely expansive in nature. The partial pressure of nitrous oxide is 31 times greater than that of nitrogen (air), so it will exit the patient’s mouth and enter the operators’ breathing space before it falls to the floor.


The following is a list of recommendations and preventive measures to minimize trace gas contamination in your dental office.14

• Establish baseline values of nitrous oxide concentrations in the office. Evaluate the ambient air using an infrared spectrophotometer.

• If desired, use time-weighted dosimetry devices to monitor exposure of office personnel to nitrous oxide over a specified period of time.

• Every 2 years send the equipment to the manufacturer for routine maintenance and evaluation.

• Visually inspect the conduction tubing and reservoir bag for cracks and tears.

• Use the soap/water test on fittings and connections to assess for gas leaks. To do this, place a few drops of dishwashing detergent in a small amount of water. Wipe some of this solution around the fittings where the gas lines attach to the flowmeter. If these areas are leaking, bubbles will form around the fittings. Wipe off the solution and tighten the lines.

• Ensure the adequacy of the evacuation system in place.

• Assess room ventilation and air exchange in the office. It may be necessary to supplement local ventilation to assist the removal of waste nitrous oxide. Be wary of air conditioners that may recirculate waste gas within the office rather than remove it. It is possible in the future that fresh air exchanges will become mandatory in offices that use nitrous oxide/oxygen sedation.

• Make sure all office personnel are educated on the facts regarding chronic exposure to nitrous oxide. Develop a hazard control team to continually assess the effectiveness of the office scavenging system.


Nitrous oxide/oxygen sedation remains a viable option for managing a patient’s pain and anxiety in the dental office. There are several advantages to its use and relatively few contraindications. Knowing how to minimize the operator’s exposure to the gas is also an important consideration. N2O/O2 sedation has a long-standing history of safety and success and it is likely that this type of sedation will be used far into the future.

It is necessary to educate the entire office team on the biohazard issues of nitrous oxide safety in the dental office and keep abreast of sound scientific literature in this area. Many states are starting to include nitrous oxide administration and monitoring in their state practice acts for dental assistants. Refer to your state practice act for current requirements in your location. Manufacturers of nitrous oxide equipment suggest periodic evaluation and routine maintenance checks.


Ann Brunick, RDH, MS, is chairperson and professor of the Department of Dental Hygiene at the University of South Dakota. She received an AA degree from the University of South Dakota, a BS degree from the University of Minnesota, and a master’s degree from the University of Missouri—Kansas City, School of Dentistry. She has served on numerous committees at the local, regional, and national levels, including the ADHA Institute for Oral Health Scholarship and Research Review Committees, the National Dental Hygiene Board Examination Construction Committee, the International Federation of Dental Hygienists’ editorial board and the ADA Commission on Dental Accreditation as a site visitor. Ms. Brunick has published numerous articles and abstracts. Her most recent work is the third edition of a textbook entitled Handbook of Nitrous Oxide and Oxygen Sedation that she co-authored with Dr. Morris Clark.

Morris S. Clark, DDS, FACD, is a nationally and internationally recognized expert on the subject of nitrous oxide/oxygen therapy. He is a graduate of the University of California School of Dentistry and completed his training in oral maxillofacial surgery at Columbia University. He is a professor at the University of Colorado School of Dental Medicine and on the faculty of the medical school there as well. He has been president of the American Society for the Advancement of Anesthesia in Dentistry and the American Dental Society of Anesthesia for the states of Colorado, Arizona, Kansas, Utah, Wyoming and New Mexico. Dr. Clark did the original clinical research on Versed (Midazolam) and Romazicon (Flumazenil), the antagonist for all the benzodiazepine class of drugs. He is on the Board of Directors for the American Dental Society of Anesthesia and a member of the American Dental Association Council on Scientific Affairs. He is co-author of the best-selling text Handbook of Nitrous Oxide and Oxygen Sedation, published by Elsevier.


1. Hart RH, Vote BJ, McGeorge AJ, et al. Loss of vision caused by expansion of intraocular perfluoropropane (c3f8) gas during nitrous oxide anesthesia. American Journal of Opthalmology. 2002;134(5):761-763.

2. Munson ES. Complications of nitrous oxide anesthesia for ear surgery. Anesthesiology. 1993;11(3):559.

3. Fleming P, Walker P. Bleomycin therapy: a contraindication to the use of nitrous oxide-oxygen psychosedation in the dental office. Pediatr Dent. 1988;10(4):345-346.

4. Frost EA. Central nervous system effects of nitrous oxide. In Eger EII, ed. Nitrous Oxide N2O. New York, 1985, Elsevier Science Publishing.

5. Clark MS, Renehan BW, Jeffers BW. Clinical use and potential biohazards of nitrous oxide/oxygen. Gen Dent. 1997;45:486-491.

6. Vaisman A. Working conditions in surgery and their effect on the health of anesthesiologists. Eksp Khir Anesteziol. 1967;3:44-49.

7. Sweeney B, et al. Toxicity of bone marrow in dentists exposed to nitrous oxide. Br Med J. 1985;291:567-569.

8. Fujinagra M, Baden JM, Mazze RI. Susceptible period of nitrous oxide teratogenicity in sprague-dawley rats. Tetrology. 1989;40:439-333.

9. Rowland AS, et al. Reduced fertility among women employed as dental assistants exposed to high levels of nitrous oxide. New Eng J Med. 1992;327:993-997.

10. Weimann J. Toxicity of nitrous oxide. Best Pract Res Clin Anesthesiology. 2003;17(1):47.

11. Myles PS, et al. A Review of the risks and benefits of nitrous oxide in current anesthetic practice. Anesth Intensive Care. 2004;32:165.

12. Weisner G, et al. High-level, but not low-level, occupational exposure to inhaled anesthetics is associated with genotoxicity in the micronucleus assay. Anesth Analg. 2001;93:118.

13. Layzer RB. Myeloneuropathy after prolonged exposure to nitrous oxide. Lancet. 1978;2:1227-1230.

14. ADA Council on Scientific Affairs, ADA Council on Dental Practice. Nitrous oxide in the dental office. J Am Dent Assoc. 1997;128:364.

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SOURCE: American Dental Assistants Association | July 2016

Learning Objectives:

• Recognize characteristics of nitrous oxide that make it desirable to use for most patients.
• Evaluate indications and contraindications for the use of N2O/O2 sedation.
• Differentiate between the facts and myths surrounding chronic exposure to nitrous oxide.
• Explain what the NIOSH and ACGIH recommended exposure limits signify.
• Identify biologic effects associated with high levels and/or misuse of nitrous oxide.
• Describe methods for detecting and assessing levels of trace gas in an outpatient setting.
• List methods for minimizing trace levels of nitrous oxide in an outpatient setting.


The author reports no conflicts of interest associated with this work.