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Paracelsus, a Swiss physician and alchemist, is credited with the earliest use of an inhalational anesthetic when he prepared a mixture of diethyl ether, alcohol, and water called sweet oil of vitriol. He described the administration of this preparation to hens that fell into what appeared to be a deep sleep from which they recovered unharmed. In 1735, Wilhelm Froben gave this substance its modern name of “ether.” Ether was used topically, particularly via the intranasal route, as a treatment of headache, nervous diseases, and fits.

Modern anesthetic practice began in 1846 at the Massachusetts General Hospital, when the dentist William Morton gave the first public demonstration of the ability of inhaled ether vapor to alleviate the pain of surgery. Oliver Wendell Holmes chose the Greek-related noun anesthesia (without feeling) to characterize the process.

Observations on circulatory and respiratory physiology eventually led to an understanding of the effects of inhalation gases and vapors. In the last decade of the 18th century, centers for the “pneumatic treatment” of disease were established in Birmingham and Bristol, England. Experiments with ether that was inhaled via a funnel and with nitrous oxide were conducted at these institutions. After Humphry Davy described his own pleasurable and exhilarating experience when he inhaled the “laughing” gas, many of his colleagues and friends inhaled nitrous oxide to experience its inebriating effects. Davy also described how inhalation of nitrous oxide relieved headache and the pain of an erupting molar tooth. Although Davy recognized the analgesic properties of nitrous oxide and its possible application for surgery, he failed to pursue the idea.

The public soon took up the use of nitrous oxide in the form of nitrous oxide frolics. Audience members at itinerant medicine shows volunteered to experience the exhilarating effects of nitrous oxide inhalation. At one such show in 1844 in Hartford, Connecticut, a man under the influence of nitrous oxide injured his leg but felt no pain. Dr. Horace Wells, a dentist in the audience that day, inhaled nitrous oxide the following day and had his partner painlessly remove a troublesome tooth. A subsequent public demonstration of the use of nitrous oxide for dental extraction had limited success, leaving his colleagues doubtful regarding its efficacy and safety and thereby impeding its general acceptance as a surgical anesthetic.

In Great Britain in 1847, James Simpson, an obstetrician, first used ether to relieve the pain of labor. He subsequently adopted chloroform for this purpose because of its more pleasant odor and more rapid induction and emergence. The clergy and other physicians opposed the concept of relieving pain during childbirth, but the method ultimately was accepted after Queen Victoria gave birth to Prince Leopold while receiving chloroform administered by John Snow.

Over the next century, several “volatile” anesthetics were introduced, including ethyl chloride in 1848, divinyl ether in 1933, trichloroethylene in 1934, and ethyl vinyl ...

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