In 1783 Joseph Priestly published his study of a drug that he had prepared, which he called “Dephlogisticated Nitrous Air”. His younger friend, Humphrey Davy studied the drug, which he called nitrous oxide, in his laboratory for 2 years and published his findings in 1800. Among his many observations he noted that four or five breaths of nitrous oxide temporarily relieved his headache from indigestion and on another occasion pain from his inflamed gum. In both cases the pain returned after a time but was less intense than originally. Davy’s colleagues in chemistry acknowledged his observations but none of them appreciated the fact that it might relieve the pain of surgery. In 1844 a medical student at New York’s College of Physicians and Surgeons, Gardner Quincy Colton found that he could earn money for his medical school expenses by attracting patrons into a rented hall and having them inhale nitrous oxide in conjunction with a lecture on chemistry. Those inhaling the gas erupted into loud laughter, which amused the audience and greatly enlivened his lecture. Horace Wells, a dentist in Hartford, Connecticut attended one of these lectures, and subsequently asked Colton to administer nitrous oxide to him while a colleague extracted his painful tooth. While Colton continued to administer nitrous oxide for years afterward for dental extractions both in the United States and England, the discovery of ether and subsequently chloroform anesthesia occupied the attentions of those involved in advancing surgical anesthesia. In 1868 Dr. E. Andrews, a Professor of Surgery at Chicago Medical School published a paper indicating that a mixture of nitrous oxide 75 % with oxygen 25 % might be useful for surgical anesthesia, and subsequently used it on some of his surgical patients. With improved methods for delivery of a nitrous oxide–oxygen mixture over the next 50 years the drug became increasingly popular as an adjuvant for clinical anesthesia. The term “balanced anesthesia ” came into the anesthesia lexicon to acknowledge the use of nitrous oxide in combination with a sedative-hypnotic (thiopental), an opiate (morphine, meperidine, etc.) and a neuromuscular blocking drug (succinylcholine, d-tubocurarine). It was widely accepted that nitrous oxide was safe for most patients so long as one avoided a hypoxic gas mixture.

In the last 30 years there has been increasing concern that nitrous oxide may not be as safe as originally thought [1]. This is not a new concern. In 1944 Ralph Waters wrote that there was a growing tendency to abandon the use of nitrous oxide because of the technical danger of delivering a hypoxic mixture and the fact that it did not produce any skeletal muscle relaxation [2]. Even in 2015 the question still arises each day in the operating rooms across the United States: Shall we use nitrous oxide on this patient or not…yea or nay? This chapter analyzes the advantages and disadvantages of nitrous oxide so that readers can decide for themselves whether there is still a place for this drug in clinical anesthesia.