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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. Its ease of use, ability to be combined with or used in conjunction with other medications, relative low cost, rapid onset, and rapid elimination have likely contributed to nitrous oxide remaining one of the most commonly used anesthetics for medical and dental purposes.1,2

Joseph Priestly 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 and was the first to coin the term “laughing gas.”1 It remained largely a recreational drug for approximately 40 years despite noting its analgesic effects and predicting surgical applications. An American Dentist by the name of Horace Wells demonstrated clinical anesthesia for the first time in 1845 at Massachusetts General Hospital by using nitrous oxide and having one of his own teeth extracted. It was later recognized that the concentrations needed for anesthesia jeopardized patients because of their potential to cause hypoxia and lead to death.1 Edmund Andrews added oxygen to the nitrous oxide mixture in 1868 to prevent the 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, a self-administered apparatus of nitrous oxide with air was introduced to facilitate childbirth.3 Seward improved on the self-administered apparatus in 1949 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.4 Ruben completed a study in 1969 of more than three million patients receiving nitrous oxide without a mishap.5 Nitrous oxide has gained widespread acceptance since then and is the most frequently used inhalational anesthetic agent. It is used in conjunction with a volatile anesthetic gas since it only possesses weak anesthetic properties. Nitrous oxide has been used experimentally in animal models after resuscitation. It has been show to offer global neuroprotection due to its blockade of the N-methyl-D-aspartate (NMDA) receptor in the brain.6

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, United Kingdom) has been used by the British Ambulance Service in a self-administered format since 1970.7 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.8


Nitrous oxide is a colorless gas at room temperature. It has a pleasant slightly sweet odor and taste. Nitrous oxide is ...

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