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Nitrous oxide (N2O) has been used for more than 150 years in medical practice for its anesthetic, analgesic, and anxiolytic properties. It is easy to administer, inexpensive, and has a rapid effect, as well as a rapid elimination. Nitrous oxide is suitable for patients of all ages and can be combined with other medications and local anesthetics. Joseph Priestley synthesized nitrous oxide in 1772, shortly after his discovery of oxygen. Humphry Davy was the first to identify the analgesic and anesthetic effects of nitrous oxide in 1799. However, it remained a recreational drug known as “laughing gas” until Horace Wells used it as an anesthetic during dental extractions at Massachusetts General Hospital in 1845. Andrews added oxygen to the nitrous oxide mixture in 1868 in order to prevent hypoxia that was commonly seen with the use of nitrous oxide. The first detailed analysis of nitrous oxide–oxygen mixtures as they apply to pain relief of angina without sedation or hypoxia was published by Stanislav Klikovich in 1881. In 1934, Minnitt introduced a self-administered apparatus of nitrous oxide with air to facilitate childbirth.1 In 1949, Seward improved on the self-administered apparatus by adding oxygen instead of air to the nitrous oxide for a more prolonged analgesia and sedation during childbirth without the possibility of inducing hypoxia.2 Ruben completed a study in 1969 of more than three million patients receiving nitrous oxide without a mishap.3 Since then, nitrous oxide has gained widespread acceptance and is the most frequently used inhalational anesthetic agent. It is used in conjunction with a volatile anesthetic gas since it only posses weak anesthetic properties. Recently, nitrous oxide has been used experimentally in animal models postresuscitation. It has been show to offer global neuroprotection due to its blockade of the N-methyl-D-aspartate (NMDA) receptor in the brain.4

Nitrous oxide–oxygen mixtures were first applied in an ambulatory setting in 1955; dentists in Denmark used them for office-based procedures. A 50:50 mixture of nitrous oxide with oxygen (Entonox, Linde Healthcare Inc., Worsley, Manchester, UK) has been used by the British Ambulance Service in a self-administered format since 1970.5 Nitrous oxide–oxygen mixtures became popular in the United States as a sedative and analgesic for use in the Emergency Department during the late 1970s.6

At room temperature, nitrous oxide is a colorless gas with a pleasant, slightly sweet odor and taste. It is heavier than air and nonflammable. When mixed with oxygen, however, it is combustible. Nitrous oxide is poorly soluble with a high minimum alveolar concentration (MAC) value. Nitrous oxide is 34 times more soluble in plasma than nitrogen. It diffuses rapidly across biologic membranes into the bloodstream (lung–blood and blood–CNS), resulting in a rapid onset (30 to 60 seconds) and short duration of action. Maximum effect occurs at approximately 2 minutes. Its duration of action lasts 2 to 5 minutes after discontinuation of the administration. Nitrous oxide does not have significant ...

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