For Students & Dentists: Nitrous Oxide – Use & Safety

In dentistry, nitrous oxide is the most commonly used inhalation anxiolytic and sedation adjunct. It reduces anxiety and pain, and memory of the treatment experienced. It is a valuable component of the armamentarium available to clinicians. When used correctly, it is predictable, effective, and safe.

Officially known as dinitrogen monoxide by the International Union of Pure and Applied Chemistry (IUPAC), nitrous oxide (an oxide of nitrogen) is a small inorganic chemical molecule with the formula N2O. It is commonly known as laughing gas, nitrous, nitro, NOS, sweet air, protoxide of nitrogen, and hyponitrous oxide. At room temperature, it is a colorless, non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anxiolytic and analgesic effects. As a general anesthetic, it is very weak and generally is not used as a single agent but is often used as a carrier gas with oxygen in combination with more potent general inhalational gases for surgical anesthesia. It is known as “laughing gas” due to its euphoric effects, a property that has led to its recreational use as a dissociative anesthetic. As an industrial gas, it is used as an oxidizer in rockets and in auto racing to increase engine output power. It is also a foaming agent for canned whipped cream in the food industry.

Nitrous oxide sedation appropriately administered is safe for normal, healthy patients, and its effects on the cardiovascular and respiratory systems are minimal. Although a mild myocardial depressant, its minor central sympathetic stimulatory effect offsets this. The fast onset and quick recovery seen with nitrous oxide/oxygen sedation is due to the rapid diffusion and saturation in blood. At a concentration of 50% to 70%, rapid uptake occurs from the alveoli to the pulmonary circulation and simultaneously creates a vacuum in the lungs that helps to pull more gas into the alveoli.

After administration is terminated, nitrous oxide is rapidly diffused back into the lungs along with oxygen and other gases. Due to this, oxygen exchange from the pulmonary circulatory system is impaired, which can result in diffusion hypoxia. When inhalation of high concentrations of nitrous oxide is discontinued, high partial pressure in blood rapidly transfers nitrous oxide to the alveoli. This dilutes the partial pressure of oxygen in the alveoli and may lead to hypoxemia. For this reason, it is conventional practice to provide the patient with 100% oxygen during the (approximately) first five minutes following discontinuation of nitrous oxide.

This concern is more theoretical than clinical, however. Hypoxemia is significant for only a matter of minutes and has been documented only when high concentrations (>70%) have been delivered by full mask or by endotracheal tube.

These conditions cannot be met with the use of conventional dental nitrous oxide machines with nasal masks, and any tendency for diffusion hypoxia is usually inconsequential. Dental N2O units will not allow greater then a 70% N2O to 30% O2 ratio as a safety feature and avoid accidental administration of greater then a 70% N2O gas.

Nevertheless, providing 100% oxygen toward the end of a dental appointment has other benefits and is advocated. This allows discontinuation while providing a waning placebo influence, and it allows expired nitrous oxide to enter the scavenging apparatus of the machine, limiting exposure of the staff and practitioner to the gas being exhaled, which is sound environmental practice.

Indications and Benefits

Nitrous oxide is the most commonly used inhalation anesthetic/sedative used in dentistry and has an excellent safety record. In medicine, the number of office based anesthesia procedures is increasing more rapidly than are hospital-based procedures. Nitrous oxide/oxygen conscious sedation is frequently used in oral surgery, particularly in the extraction of third molars, periodontal surgery, implant placement, and in patients with behavioral or developmental issues. N2O can be used for anxiolysis or conscious sedation.


Anxiolysis is the prevention or reduction of anxiety. An anxiolytic is a medication or other intervention that inhibits anxiety. The main indication for nitrous oxide is to diminish anxiety and fear in patients, and this is often accomplished using low-dose N2O and high-dose oxygen. Low-dose N2O can also induce relaxation of psychological tension in dental patients who have dental phobias. Also, high-dose oxygen contributes to manage pre-syncope due to pain stimuli. In particular, phobic and fearful children who are too young and/or unable to cooperate or overcome their fears are candidates for N2O use to enable necessary care without further trauma. Nitrous oxide/oxygen significantly improves cooperation in fearful children. Restraint for children is an option that is controversial and traumatic, whereas the use of N2O/O2 as an anxiolytic reduces fear and anxiety and alleviates pain, which may encourage rather than discourage future cooperation.

Indications and relative/absolute contraindications for nitrous oxide

Indications for nitrous oxide:

1. Mildly apprehensive patient

2. The frightened child

3. To reduce awareness of time and fatigue

4. To reduce dental stress

5. To control gagging

6. When requested by the patient

Relative contraindications to nitrous oxide:

1. Pulmonary disease

2. Respiratory infections

3. Pregnancy

4. Psychiatric patients

5. Immune-compromised patient

6. Multiple sclerosis

7. Patient using marijuana or hallucinogenic drugs

8. Blocked middle ear

9. Highly apprehensive patient

10. Repeated exposures less than one week apart

Absolute contraindications to N2O:

1. Nasal obstruction

2. Completely uncommunicative, either due to disability or  language barrier

3. Increased intracranial pressure

4. As a substitute for local or general anesthesia

5. Patient refusal

6. Active substance abuse or recovered substance abuser

7. Lack of gas recovery affecting dental team

Conscious Sedation

Conscious sedation is the use of a combination of drugs to induce relaxation and provide some analgesia during a medical or dental procedure. Nitrous oxide/oxygen reduces pain and anxiety in anxious and fearful patients, including those who are phobic and unreceptive to other techniques and for whom the only other alternative may be general anesthesia. Conscious sedation has been found to be efficacious, reliable, and more cost-effective than general anesthesia. Pharmacological agents and techniques used in dentistry for sedation include enteral sedation with benzodiazepines or intravenous conscious sedation using a variety of agents including benzodiazepines, narcotic analgesics, and hypnotic/amnesic agents.

With multiple drug regimens, extra caution must be exercised. In surveys of patients not visiting the dentist, fear of needles and pain were responsible for up to 28% and 21% of adult patients respectively. A number of techniques are available to reduce fear and anxiety and increase cooperation with treatment. These include behavioral techniques and communication. Hypnosis has been used to reduce fear, the perception of pain, and to alter memory, although not all patients are suggestible for hypnosis. Acupuncture and acupressure have also been used. Functional and cognitive deficits can make dental treatment difficult for special needs patients. As with fearful patients, behavioral interventions may be helpful. In some circumstances, physical support or protective stabilization is used. Nitrous oxide/oxygen sedation is an effective method to enable treatment in patients with reduced mental development as well as other special needs patients. Consideration must be given to the ability of the patient to communicate and understand the procedure.


As with any inhalation drug, there are both relative and absolute contraindications with N2O. These include patients with respiratory illnesses such as chronic obstructive pulmonary disease (COPD) and asthma, nasal obstruction, and pregnancy, among others.

COPD: Patients with chronic obstructive pulmonary disease have both a reduced ability to move gases into and out of the lungs because of reversible bronchospasm and irreversible bronchial obstruction. Hypoxemia and hypercarbia can result from chronic hypoventilation or poor gas exchange across the respiratory membranes. Some authorities suggest that nitrous oxide should be avoided in patients who have significant chronic obstructive pulmonary disease. Reasons cited include depression of hypoxemic drive: since high oxygen concentrations are delivered with nitrous oxide, its use may remove the stimulus for hypoxemic drive. However, if the principles of moderate sedation are followed, the patient can always be instructed to breathe more deeply.

Asthma: All inhalation agents share a tendency to increase respiratory rate but decrease tidal volume. Their net influence on ventilation is reflected as the degree of hypercapnia that occurs during administration. Nitrous oxide is distinguished from other agents in that it does not reduce net ventilation. Since N2O is not irritating to the tracheobronchial tree, asthma is not a contraindication to the use of N2O, provided the patient is not having an attack.

In fact, there is a benefit to administering nitrous oxide since in many asthmatics, the primary precipitant appears to be emotional stress, especially in children. However, no dental procedure should be attempted if the patient is having respiratory difficulty due to asthma.

Nasal obstruction: The inability to use a nasal mask is an absolute contraindication to the use of nitrous oxide. Generally, such patients fall into one of two categories:

(1) those who cannot inhale adequately through the nose because of anatomic and/or disease-induced nasopharyngeal obstructions, and (2) those who cannot tolerate and sustain placement of the nasal mask because of psychological and/or cognitive disturbances.

Examples include patients who are severely phobic, cognitively impaired, and pediatric patients. Additional examples include patients with a deviated septum, nasal polyps, upper respiratory infection, allergic rhinitis, and severe sinusitis. In this latter regard, any compromise in patency of the eustachian tube may lead to pressure increases within the middle ear, as previously mentioned. In fact, it has been suggested that any recent surgery of the ear presents a contraindication for nitrous oxide use. Any nasal obstruction will severely restrict the patient’s ability to breathe through the nose. Since nitrous oxide must be administered via a nasal mask, this becomes a relative contraindication depending on the severity of the obstruction. Patients who are “mouth breathers,” either due to nasal restriction or simply from habit, do not do well attempting to breathe through the nasal mask and often can not exchange well enough nasally to be comfortable.

Multiple sclerosis: Multiple sclerosis (MS) is a disease characterized by nerve demyelination, especially in the central nervous system. Neurologic symptoms of weakness, incoordination, paresthesia, and speech disturbances are common.

Neither occupational exposure to anesthetic agents nor general anesthesia or usage of nitrous oxide has any impact on MS risk and is safe also for people with a genetic susceptibility to the disease. However, further studies would be valuable in order to clarify whether other forms of organic solvents contribute to the triggering of MS.

Pregnancy: Nitrous oxide readily enters fetal circulation, and because of the possible toxicity of N2O to cells undergoing mitosis, pregnant patients, especially in the early weeks of pregnancy, should not receive nitrous oxide electively. However, necessary emergency dental care should not be denied a pregnant patient, and if it is determined that N2O is necessary to reduce stress, it may be used following consultation with the obstetrician. Widely used in Europe as a labor analgesic, nitrous oxide (N2O) is making a dramatic return in the United States.

Psychiatric patients: Psychiatric patients may present sedated due to their normally prescribed medication. It is best to consult the patient’s psychiatrist and/or treating physician before administering N2O. If permitted, these patients should be titrated carefully, with close monitoring, as their reactions may be unpredictable.

Inability to communicate: Since much of the patient monitoring with N2O conscious sedation is done verbally, being unable to communicate with the patient becomes a contraindication to the use of N2O. This would include severely mentally challenged patients, very young patients, language barriers, or any condition that prevents easy exchange of thoughts between doctor and patient.

Hallucinogenic drugs: The use of hallucinogenic drugs such as marijuana is contraindicated for N2O. Marijuana can enhance an already pleasant situation, and conversely increase the dysphoria of an already stressful situation. Following heavy use of marijuana, the drug may remain in the circulation for seven or more days due to its very long half-life. Hallucinogenic drugs act in a similar manner, only with a great deal more intensity, and patients may experience frightening hallucinations.

Intracranial pressure: Nitrous oxide has been shown to increase intracranial pressure in patients with certain injuries and intracranial disorders. Therefore, N2O should not be administered to these patients. The role of vascular tone in determining cerebral perfusion pressure is increasingly being appreciated. It has been suggested that zero flow pressure, the arterial pressure at which blood flow ceases, represents the effective downstream pressure of the cerebral circulation. Nitrous oxide is a cerebral vasodilator and may therefore decrease zero flow pressure and increase cerebral perfusion pressure. However, these effects may be opposed by the increase in intracranial blood volume produced by cerebral vasodilation.

Highly apprehensive patients: Since N2O is a relatively weak agent, it should not be used alone in an apprehensive patient, or as a substitute for anesthesia.

Blockages: Because nitrous oxide has a solubility coefficient that is 35 times higher than nitrogen, it can quickly displace nitrogen in any closed cavity, dramatically increasing the pressure within. Therefore, conditions such as blocked Eustachian tubes, blocked bowel, acute blocked sinusitis and pneumothorax that allow a rapid pressure increase in a closed body cavity, leading to pain, contraindicates the use of N2O.

Depression of bone marrow activity: Exposure to N2O causes a depression of bone marrow activity, resulting in a reduction in the production of erythrocytes and leukocytes. However, since normal marrow contains a “store” of mature cells sufficient to supply several days’ needs, and the marrow recovers to return to production within 3 to 4 days, no hematologic change is seen following an isolated anesthetic or conscious sedation exposure to nitrous oxide. However, a second exposure within this period of time will extend inhibition of synthesis, which may exceed the safety factor of stored cells. Since repeated exposures at close intervals may produce leukopenia, frequent exposure to nitrous oxide (less than one week between administrations) should be avoided.

Immunocompromised: Because N2O seems to reduce chemotaxis (the motility of leukocytes) toward foreign proteins such as bacteria, as well as to reduce leukocyte action against tumor cells, patients with compromised immune systems should avoid nitrous oxide unless urgently required. This would include patients with AIDS or those taking immunosuppressive drugs.

Unwilling patients: N2O should never be used on an unwilling patient. If, after explaining the benefits, the patient does not want N2O, it should not be used.

Dental team exposure and unintended inhalation

In a review of the advantages and harmful effects of N2O in dental management by Ogawa and Misaki, while N2O inhalation sedation is effective for dental treatment, leakage of N2O in the operatory affects the health of the dental staff members. In addition to inadequate ventilation and scavenging systems, other equipment issues that may affect team members include equipment malfunctions, failures, and leaks due to poor connections.

In a study by Staubli et al, vitamin B12 levels were measured in anesthetic staff applying nitrous oxide. It showed reduced vitamin B12 plasma levels by measuring homocysteine, methylmalonic acid, vitamin B12, blood count, and the MTHFR C677T genotype. The study concluded that, provided a safety demand valve is used, the use of nitrous oxide (50%–70%) is safe for the vitamin B12 status of medical personnel.


Nitrous oxide is a valuable agent that assists patients who are anxious and fearful. It has an excellent safety record when used for anxiolysis and conscious sedation. There are, however, certain parameters that must be followed to ensure that every patient receives the proper and correct mode of treatment in this area.

Reference: This article has been written by Ian Shuman, DDS, MAGD, AFAAID.


3 thoughts on “For Students & Dentists: Nitrous Oxide – Use & Safety

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