Nitrous Oxide

Nitrous oxide is a colorless, odorless to sweet-smelling inorganic gas that was first used in surgical and dental anesthesia in the mid-1800s.^{1, 2}  Today, the combination of inhaled nitrous oxide and oxygen, when used appropriately, can be a safe and effective means of managing pain and anxiety in dentistry.³  Referred to as “conscious sedation,” “relative analgesia,” or “nitrous oxide-oxygen sedation,”³ inhaled nitrous oxide-oxygen is the most used gaseous anesthetic in the world⁴ and a 2007 survey by the ADA estimated that 70% of dental practices using any form of sedation employed nitrous oxide-oxygen sedation.⁵

Inhalational anesthetics, including nitrous oxide-oxygen, are absorbed and distributed as the result of pressure gradients in the lungs and equilibrate when the tension of inspired gas equals that in alveoli, blood, and tissues.¹ Gases that have low solubility in blood and adipose tissue, such as nitrous oxide, will achieve blood tension and equilibrate more rapidly; this provides the driving force for inhalation agents to enter the brain, where anesthetic action occurs.¹ Nitrous oxide has the fastest onset among inhalation agents¹ and is transported in blood as free gas; it does not combine with hemoglobin, and it does not undergo biotransformation.¹ Systemic elimination occurs with pulmonary exhalation; its low solubility allows nitrous oxide to be removed rapidly from the body.¹

Nitrous oxide irreversibly oxidizes vitamin B12, reducing the activity of B12-dependent enzymes such as methionine and thymidylate synthetases.¹  This is the likely mechanism for adverse health effects reported in those individuals who are chronically exposed to trace amounts of the drug, such as infertility, spontaneous abortion, blood dyscrasias, and neurologic deficits.¹

According to the ADA sedation and anesthesia guidelines (adopted in October 2016),⁶ inhaled nitrous oxide-oxygen, when used in combination with sedative agent(s) may produce minimal, moderate, or deep sedation, or general anesthesia.

There are two types of nitrous oxide-oxygen delivery systems: portable tanks on yoke stands that can be wheeled between operatories and larger, fixed-tank systems that are connected with a manifold system that can serve several operatories.²  Nitrous oxide-oxygen delivery systems are typically limited to a maximum of 70% nitrous oxide and 30% oxygen delivery; this helps ensure that the patient is receiving at least 9% more oxygen than is found in ambient room air.²

Although there is an inherent safety margin for administration of nitrous oxide-oxygen sedation, there are at least 12 delivery system audio and visual safety features that have been developed to help avoid adverse events during administration (Table).²  Practitioners should know how to maintain these features and to immediately remove the patient’s face mask to allow for breathing of room air when any of these safety features is suspected of failing.²

Table.  Safety Features of Nitrous Oxide-Oxygen Delivery Systems²

Safety Feature	Brief Description
Alarms	Audio and/or visual alarms (e.g., low- or high-oxygen and nitrous oxide pressure alarms)
Color Coding	Gas tanks, knobs, and hoses are coded by color (standardized nationally, but not necessarily internationally)
Diameter index safety system	A standard for noninterchangeable, removable connections for use with medical gases helps ensure that the appropriate gas flows through the appropriate tubing and cannot be interchanged
Emergency air inlet	An inlet designed to remain closed as long as gases are being administered to the patient; however, when the oxygen fail-safe system turns the gases off, ambient air is allowed to enter the system so that the patient can continue to breathe through the nasal hood or face mask
Locks	According to national fire codes, nitrous oxide and other compressed gases must be kept in locked rooms;  many manufacturers supply additional locks for the machines at the tanks, the manifold, or the mixer level to prevent staff members from accessing nitrous oxide inappropriately
Oxygen fail-safe system	The oxygen fail-safe system is designed so that the nitrous oxide supply will be turned off automatically when oxygen delivery is compromised or depleted; delivery systems are required to provide a minimum oxygen liter flow that ensures that 2.5 to 3.0 liters of oxygen per minute is the minimum amount being administered and that concentrations of oxygen never fall below 30% during gas delivery
Oxygen flush button	A mechanism that allows for 100% oxygen to be administered through a reservoir bag in the event of an emergency; when the button is pressed, the oxygen flush valve engages, and the system delivers oxygen straight from the pipeline or tank regulator at 45 to 50 psi at a flow rate between 35 and 75 L/min
Pin-index safety system	Pins protruding from the gas tank yokes have a unique configuration that fits into corresponding holes in the tank valves that help prevent the accidental attachment of a nonoxygen tank to the oxygen attachment portal
Quick connect for positive-pressure oxygen	In an emergency situation in which positive-pressure oxygen is required (e.g., to augment cardiopulmonary resuscitation), quick-connect compatibility helps ensure immediate access to positive-pressure oxygen anywhere in the office
Reservoir bag	An inflatable rubber reservoir bladder into which fresh gas entering the circuit is conveyed; the bag is filled gradually as gases enter the circuit and is deflated with inhalation

Adopting appropriate work practices and following recommendations from the Council on Scientific Affairs (CSA) may help dental offices safely use nitrous oxide-oxygen.⁷ Following are recommendations developed by the CSA:⁷

• Every nitrous oxide delivery system should be equipped with a scavenging system. A flow meter (or equivalent measuring device) should be easy to see and well maintained to ensure accuracy. The system also should have a vacuum pump with the capacity for up to 45 liters of air per minute per workstation. The system also should come with masks in various sizes to ensure a proper fit for individual patients.

• Vent the vacuum and ventilation exhaust fumes outside (for example, through a vacuum system). Do not place exhaust system in the vicinity of the fresh-air intake vents. Ensure that the general ventilation provides good room-air mixing. Chronic occupational exposure—several hours a week—to unscavenged nitrous oxide has been associated with adverse health effects.³

• Test the pressure connections for leaks every time the nitrous system is first turned on and each time a gas cylinder is changed. High-pressure line connections should be tested for leaks at least quarterly. You can use a soap solution applied to the lines and connections to test for leaks. Alternatively, you can purchase a portable infrared spectrophotometer to test these connections.

• Before the initial use of the system for the day, inspect all of the system components—reservoir bag, tubings, masks, connectors—for wear, cracks, holes or tears. Replace any damaged pieces.

• Once all of the components have passed inspection, you can connect the mask to the tubing and turn on the vacuum pump. Ensure that the flow rate is correct—up to 45 liters per minute or according to the manufacturer’s recommendation.

• The mask should be properly fitted to each patient. Check that the reservoir bag does not over- or underinflate while the patient is breathing oxygen, before the nitrous is administered.

• Ask the patient to limit talking during administration of the nitrous and to try to breathe through his or her nose—avoid breathing through the mouth if possible.

• During administration, watch for changes in the tidal volume of the reservoir bag also keep an eye on the vacuum pump flow rate.

• After the procedure, deliver 100% oxygen to the patient for 5 minutes before removing the mask. This will purge the system of any residual nitrous oxide and will help the patient clear the drug.

• Periodically (semiannually is suggested), personnel—particularly those who work with the nitrous oxide delivery—can be assessed for exposure. This can be done by asking the staff members to wear personal dosimetry badges or by placing an infrared spectrophotometer in the room.

National Institute for Occupational Safety and Health (NIOSH) research indicates that controls such as system maintenance, proper ventilation and good work practices can effectively reduce nitrous oxide concentrations in dental operatories to approximately 25 ppm (45 milligrams per cubic meter) during analgesia administration (i.e., the exposure limit recommended by NIOSH).⁸

Although there is no formal Occupational Safety and Health Administration (OSHA) standard on nitrous oxide or anesthetic gases, nitrous oxide is included in the OSHA guideline, Anesthetic Gases: Guidelines for Workplace Exposures.⁹

1. Becker DE, Rosenberg M. Nitrous oxide and the inhalation anesthetics. Anesth Prog 2008;55(4):124-30; quiz 31-2.
2. Donaldson M, Donaldson D, Quarnstrom FC. Nitrous oxide-oxygen administration: when safety features no longer are safe. J Am Dent Assoc 2012;143(2):134-43.
3. Howard WR. Nitrous oxide in the dental environment: assessing the risk, reducing the exposure. J Am Dent Assoc 1997;128(3):356-60.
4. Malamed SF, Clark MS. Nitrous oxide-oxygen: a new look at a very old technique. J Calif Dent Assoc 2003;31(5):397-403.
5. American Dental Association Survey Center. 2007 Survey of Current Issues in Dentistry: Surgical Dental Implants, Amalgam Restorations, and Sedation: American Dental Association; 2008.
6. American Dental Association. Guidelines for the Use of Sedation and General Anesthesia by Dentists.  October 2016.  Accessed January 23, 1017.
7. Nitrous oxide in the dental office. ADA Council on Scientific Affairs; ADA Council on Dental Practice. J Am Dent Assoc 1997;128(3):364-5.
8. The National Institute for Occupational Safety and Health (NIOSH). Control of Nitrous Oxide in Dental Operatories (DHHS/NIOSH Publication No. 96-107). U.S. Department of Health & Human Services. Accessed January 18, 2017.
9. OSHA Directorate of Technical Support and Emergency Management. Anesthetic Gases: Guidelines for Workplace Exposures. U.S. Department of Labor 1999. Accessed January 23, 2017.

Professional Resources

• ADA Guidelines for the Use of Sedation and General Anesthesia by Dentists (PDF)
• Nitrous Oxide Monitoring Device and Scavenging System Vendor List (PDF)
• ADA Online Continuing Education: Managing Sedation Complications

Search JADA for articles related to nitrous oxide

• Association Report: Nitrous Oxide in the Dental Office (ADA Council on Scientific Affairs, Council on Dental Practice 1997)
• Nitrous Oxide in the Dental Environment: Assessing the Risk, Reducing the Exposure (Howard 1997)
• Nitrous Oxide–Oxygen Administration (Donaldson et al. 2012)

ADA Library Services

Patient Resources

• ADA MouthHealthy: Nitrous Oxide
• JADA “For the Patient” page: Anesthesia for the Dental Visit (May 2001)

American Academy of Pediatric Dentistry (AAPD):

• Recommendations/Best Practices: Use of Nitrous Oxide for Pediatric Dental Patients (2018)
• Oral Health Policies: Policy on Minimizing Occupational Health Hazards Associated with Nitrous Oxide (2018)  

National Institute for Occupational Safety and Health (NIOSH):

• Control of Nitrous Oxide in Dental Operatories
• Controlling Exposures to Nitrous Oxide During Anesthetic Administration

Occupational Safety and Health Administration (OSHA):

• Anesthetic Gases: Guidelines for Workplace Exposures