Nitrous oxide is an odorless, colorless, non-flammable gas. While nitrous oxide is not flammable, it will support combustion to the same extent as oxygen does. It leads to a state of euphoria explaining its nickname ‘laughing gas.’ Nitrous oxide is the least potent inhalational anesthetic. Nitrous oxide requires a concentration of 104% to reach one minimum alveolar concentration (MAC). Thus it cannot be a sole anesthetic agent, and it is often combined with a more potent and volatile anesthetic. The combination of analgesic and anesthetic effects make nitrous oxide a valuable adjunct. Nitrous oxide has a low blood solubility (blood-gas partition coefficient of 0.47) leading to quick onset and offset. The low solubility leads to a concentrating effect for additionally administered volatile agents in the lungs and is known as the second gas effect. 
Nitrous oxide can be used for general anesthesia, procedural sedation, dental anesthesia, and to treat severe pain. Nitrous oxide's potent analgesic properties can be used to provide analgesia in settings such as the obstetrical ward or emergency department. In these settings it is often administered as a 50% mixture with oxygen.
Compared to other anesthetic agents, nitrous oxide causes minimal effects on respiration and hemodynamics. It leads to decreased tidal volume and increased respiratory rate but has a minimal effect on overall minute ventilation. Nitrous oxide leads to direct myocardial depression, but this effect is reduced by nitrous oxide's sympathetic stimulation and the net effect is minimal. Unlike other volatile anesthetics, nitrous oxide has no muscle relaxation properties.
Nitrous oxide has multiple supraspinal and spinal targets. The anesthetic effect of nitrous oxide is through non-competitive NMDA inhibition in the central nervous system. The analgesic effects occur through the release of endogenous opioids that act on opioid receptors; its analgesic actions are like morphine. The anxiolytic effects are through GABA-A activation. Nitrous oxide has a central sympathetic stimulating activity which supports blood pressure, systemic vascular resistance, and cardiac output. Nitrous oxide stimulates cerebral blood flow and increases intracranial pressure. 
Nitrous oxide is administered via inhalation. It can be given with a simple face mask, laryngeal mask airway, or an endotracheal tube. Excretion of nitrous oxide is primarily unchanged through the lungs. A small amount diffuses through the skin.
Adverse effects of nitrous include:
Many contraindications to nitrous use are relative and may vary based on the provider. These include:
No specific monitoring is required for nitrous oxide use. An in-line oxygen analyzer with an alarm should be utilized to prevent delivery of a hypoxic gas mixture. Modern anesthetic machines have fail-safe mechanisms to prevent this from occurring (nitrous oxide-oxygen proportioning systems). Standard ASA monitoring should be utilized when administering nitrous oxide for any indication.
While nitrous oxide inactivates methionine synthase, intraoperative use results in a transient metabolic abnormality that soon reverses upon replacement of the degraded enzyme.
When nitrous oxide is used in recurrently (during occupational exposure or as a drug of abuse), it may lead to megaloblastic anemia with neurologic dysfunction. This situation also may occur in patients with an unrecognized cobalamin deficiency (vegans, pernicious anemia, hereditary disorders of cobalamin and folate metabolism).
Nitrous oxide is a widely used option for labor analgesia in other countries. One reason for limited use in the United States is due to the limited availability of anesthesia coverage. Nitrous oxide administration and management by nursing staff has been shown to be a safe, cost-effective option for labor analgesia. The pharmacy should verify the dosing and administration times when nitrous oxide is in use and alert the ordering clinician or nursing staff of any issues or potential interactions. [Level 5]
Administration of nitrous oxide by registered nursing staff has also been used to provide procedural sedation in pediatric radiology and resulted in fewer adverse effects and a quicker return to baseline compared with oral midazolam. (level 5 evidence)
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