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Nitrous oxide: Drug information

Nitrous oxide: Drug information
(For additional information see "Nitrous oxide: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Dental Gases;
  • General Anesthetic
Dosing: Adult

Surgical sedation and analgesia: Concentrations of 25% to 50% nitrous oxide with oxygen. For general anesthesia, concentrations of 40% to 70% via mask or endotracheal tube. Minimal alveolar concentration (MAC), which can be considered the ED50 of inhalational anesthetics, is 105%; therefore delivery in a hyperbaric chamber is necessary to use as a complete anesthetic. When administered at 70%, reduces the MAC of other anesthetics by half.

Dental: Sedation and analgesia: Concentrations of 25% to 50% nitrous oxide with oxygen

Dosing: Pediatric

Refer to adult dosing.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Supplied in blue cylinders

Generic Equivalent Available: US

Yes

Use: Labeled Indications

Sedation, analgesia, and amnesia; principal adjunct to inhalation and intravenous general anesthesia

Medication Safety Issues
High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined.

Cardiovascular: Hypotension

Central nervous system: Central nervous system stimulation, confusion, dizziness, headache

Gastrointestinal: Nausea and vomiting

Respiratory: Apnea

Contraindications

Hypersensitivity to nitrous oxide or any component of the formulation; nitrous oxide should not be administered without oxygen

Use is considered contraindicated in patients having undergone vitreoretinal surgery and presence of intraocular gas bubble (Lee, 2004; Fu, 2002).

Warnings/Precautions

Concerns related to adverse effects:

• Addictive: May be associated with abuse and/or addiction.

• Body space volume expansion: Both compliant (eg, bowel gas, pneumothorax) and poorly compliant (eg, middle ear) body spaces may be prone to changes in volume due to nitrous oxide transfer; avoid use in pneumothorax, pneumocephalus, middle ear surgery, or bowel obstruction (Miller 2010; Ohryn 1995; Sprehn 1992).

• Bone marrow suppression: Prolonged use may produce bone marrow suppression; patients with vitamin B12 deficiency (pernicious anemia) and those with other nutritional deficiencies (alcoholics) are at increased risk.

• Nausea/vomiting: Occurs postoperatively in ~15% of patients.

• Neurologic effects: Prolonged use may produce neurologic dysfunction; patients with vitamin B12 deficiency (pernicious anemia) and those with other nutritional deficiencies (alcoholics) are at increased risk.

Disease-related concerns:

• Vitreoretinal surgery: Detached retina and other ocular disorders treated with vitreoretinal surgery where intraocular gas was used: Nitrous oxide can increase intraocular pressure which may result in retinal artery occlusion, ischemia, or optic nerve damage and vision loss in these patients. Nitrous oxide should not be used in patients who have had an intravitreal gas bubble unless it can be confirmed that the bubble has been completely resorbed (Fu, 2002; Lee, 2004).

Other warnings/precautions:

• Oxygen use: Oxygen should be briefly administered during emergence from prolonged anesthesia with nitrous oxide to prevent diffusion hypoxia.

Metabolism/Transport Effects

None known.

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Bupivacaine: Nitrous Oxide may enhance the adverse/toxic effect of Bupivacaine. Specifically, the risk of methemoglobinemia may be increased. Risk C: Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Isoflurane: May enhance the CNS depressant effect of Nitrous Oxide. Nitrous Oxide may enhance the therapeutic effect of Isoflurane. Specifically, isoflurane MAC values may be decreased. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrexate: Nitrous Oxide may enhance the adverse/toxic effect of Methotrexate. Risk X: Avoid combination

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Reproductive Considerations

Infertility has been reported following prolonged occupational exposure. This risk is related to dose and duration of exposure and is decreased with proper administration procedures (Becker 2008; Rooks 2011; Zafirova 2018).

Pregnancy Considerations

Nitrous oxide crosses the placenta.

Concentrations of nitrous oxide in the fetal circulation are ~80% of those in the maternal plasma. The half-life in the neonate is ~3 minutes and it is quickly eliminated from neonatal lungs with the onset of breathing (Rooks 2011).

Spontaneous abortion and congenital abnormalities have been reported in health care providers following prolonged occupational exposure (Becker 2008; Brodsky 1986; Rooks 2011). However, these adverse events are related to dose and duration of exposure and risks are decreased with proper administration procedures (Rooks 2011; Zafirova 2018). Short duration of exposure to the pregnant women during obstetric procedural anesthesia is not associated with an increased risk of adverse events to the fetus (Neuman 2013).

Nitrous oxide is used in labor analgesia (ACOG 209 2019; Collins [AWHONN 2018]; Likis 2014; Rooks 2011; Rosen 2002) and may be used when needed for dental treatments that cannot be postponed during pregnancy (Becker 2008). Consider suspending use of nitrous oxide for labor analgesia in patients with coronavirus disease 2019 (COVID-19) due to insufficient data related to physiologic safety; patients who are confirmed to be COVID-19 negative may continue to be offered nitrous oxide an option for labor analgesia (ACOG 2020).

The ACOG recommends that pregnant women should not be denied medically necessary surgery, regardless of trimester. If the procedure is elective, it should be delayed until after delivery (ACOG 775 2019).

Breastfeeding Considerations

Nitrous oxide was not found to influence the initiation or continuation of breastfeeding when used during labor (Zanardo 2017).

The Academy of Breast Feeding Medicine recommends postponing elective surgery until milk supply and breastfeeding are established. Milk should be expressed ahead of surgery when possible. In general, when the child is healthy and full term, breastfeeding may resume, or milk may be expressed once the mother is awake and in recovery. For children who are at risk for apnea, hypotension, or hypotonia, milk may be saved for later use when the child is at lower risk (ABM [Reece-Stremtan 2017]).

Mechanism of Action

General CNS depressant action; may act similarly as inhalant general anesthetics by stabilizing axonal membranes to partially inhibit action potentials leading to sedation; may partially act on opiate receptor systems to cause mild analgesia; central sympathetic stimulating action supports blood pressure, systemic vascular resistance, and cardiac output; it does not depress carbon dioxide drive to breath. Nitrous oxide increases cerebral blood flow and intracranial pressure while decreasing hepatic and renal blood flow; has analgesic action similar to morphine.

Pharmacokinetics

Onset of action: Inhalation: 2-5 minutes

Absorption: Rapid via lungs; blood/gas partition coefficient is 0.47

Metabolism: Body: <0.004%

Excretion: Primarily exhaled gases; skin (minimal amounts)

Brand Names: International
  • Dusikov (HR);
  • Maxicool (IL);
  • Niontik (DE);
  • Niontix (CZ, DK, FI, IS, LT, NL, NO, PT, RO, SE, SI, SK);
  • Nitrous EP (BD)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. American College of Obstetricians and Gynecologists (ACOG). ACOG committee opinion no. 775: nonobstetric surgery during pregnancy. Obstet Gynecol. 2019;133(4):e285-e286. [PubMed 30913200]
  2. American College of Obstetricians and Gynecologists (ACOG). ACOG practice bulletin no. 209: obstetric analgesia and anesthesia. Obstet Gynecol. 2019;133(3):e208-e225. [PubMed 30801474]
  3. American College of Obstetricians and Gynecologists (ACOG). COVID-19 FAQs for obstetrician-gynecologists, obstetrics. https://www.acog.org/clinical-information/physician-faqs/covid-19-faqs-for-ob-gyns-obstetrics. Accessed January 6, 2021.
  4. Babich S and Burakoff RP, “Occupational Hazards of Dentistry. A Review of Literature From 1990,” N Y State Dent J, 1997, 63(8):26-31.
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