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Nitrous oxide, or laughing gas, is used as an adjuvant for general anesthesia, an anesthetic and analgesic agent for minor procedures, and a propellant in many commercial products, such as whipped cream and cooking oil spray. ("Whippets" are small cartridges of nitrous oxide that can be purchased at restaurant supply stores, grocery convenience stores, and "head shops.") Nitrous oxide is used by many US dentists, in some cases without adequate scavenging equipment. Abuse of nitrous oxide is not uncommon in the medical and dental professions.


  1. Acute toxicity after exposure to nitrous oxide is caused mainly by asphyxia if adequate oxygen is not supplied with the gas.

  2. Chronic toxicity to the hematologic and nervous systems results from inactivation of vitamin B12 after irreversible oxidation of its cobalt atom. Vitamin B12 is required for the synthesis of methionine from homocysteine and for the production of tetrahydrofolate. Methionine is essential for myelin production, and tetrahydrofolate is essential for DNA synthesis. Use of nitrous oxide can precipitate neurologic symptoms in patients with subclinical B12 or folic acid deficiency.

  3. Adverse reproductive outcomes have been reported in workers chronically exposed to nitrous oxide.


The toxic dose is not established. Chronic occupational exposure to 2,000 ppm nitrous oxide produced asymptomatic but measurable depression of vitamin B12 in dentists. The ACGIH-recommended workplace exposure limit (TLV-TWA) is 50 ppm (90 mg/m3) as an 8-hour time-weighted average.


  1. Signs of acute toxicity are related to asphyxia, and include headache, dizziness, confusion, syncope, seizures, and cardiac arrhythmias. Interstitial emphysema and pneumomediastinum have been reported after forceful inhalation from a pressurized whipped cream dispenser.

  2. Chronic nitrous oxide abuse may produce megaloblastic anemia, thrombocytopenia, leukopenia, peripheral neuropathy, and myelopathy (especially posterior column findings), similar to the effects of vitamin B12 deficiency. Symptoms of neuropathy (eg, ataxia) are often the presenting complaints and physical examination may reveal abnormal vibratory sensation and proprioception.


Is based on a history of exposure and clinical presentation (eg, evidence of asphyxia and an empty can or tank). It also should be considered in a patient with manifestations suggesting chronic vitamin B12 deficiency but with normal vitamin B12 levels.

  1. Specific levels. Specific levels are not generally available and are unreliable owing to off-gassing.

  2. Other useful laboratory studies include CBC with manual differential, vitamin B12, folic acid, nerve conduction studies, and MRI if the patient has neuropathy. Elevated homocysteine and methylmalonic acid levels have been documented in nitrous oxide abusers who had normal vitamin B12 levels.


  1. Emergency and supportive measures

    1. Maintain an open airway and assist ventilation if necessary (see Airway). Administer high-flow supplemental oxygen.

    2. After significant asphyxia, ...

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