DEVELOPMENT OF INHALATION AGENTS

Chloroform

Within a year after the introduction of ether anesthesia, the search had already begun for other agents that could anesthetize without some of the problems associated with ether. Although ether was a remarkably safe agent, even when administered by untrained hands, there were disadvantages, which included flammability, a prolonged induction, unpleasant odor that was persistent, and a high incidence of nausea and vomiting. James Young Simpson (1811–1870), an obstetrician from Edinburgh, Scotland, used ether in 1846 but was determined to find a better agent. As early as January of 1847, he began experimenting with a variety of different solvents and volatile liquids.^[125]

The physician David Waldie, a contemporary of Simpson at Edinburgh Medical School who was practicing in Liverpool, England, suggested chloroform as an alternative agent. Synthesized independently by Samuel Guthrie^[126] (1782–1848), Eugene Soubeiran^[127] (1787–1858), and Justus von Liebig^[128] (1803–1873) in 1831, it had never been tested in humans as an inhaled anesthetic. Marie Jean Flourens ^[129] (1794–1867) had used chloroform in dogs while studying the stages in the depression of the central nervous system by chloroform and ether. Simpson and a group of friends learned of the surprising potency of chloroform at a dinner party hosted by Simpson on September 4, 1847. Dinner was followed by the experimental inhalation of volatile drugs, and the use of chloroform was followed by stupor and coma by several participants, including Simpson. Simpson promoted chloroform vigorously, and its use was widely accepted in England. As an obstetrician, he advocated its use during labor, promoting, along with others,^[130] the employment of analgesics during parturition. Initially, his views conflicted with those of medical authorities who considered it unsafe during labor and with those of religious authorities who opposed it on theologic grounds. Edinburgh had a black history on the issue of pain relief during childbirth. In 1591, a young woman named Euphanie Macalyane was burned alive as punishment for seeking pain relief during labor on direct order from the King of Scotland, James VI.^[131] Simpson was not a timid man and met the religious controversy with direct quotations from the Bible that appeared to support his views (Genesis 2, 21: "and the Lord God caused a deep sleep to fall upon Adam, and he slept: and he took one of his ribs, and closed up the flesh instead thereof.").

Chloroform was used widely in England, but controversy developed about its safety, particularly in otherwise healthy subjects, those in whom a physician would not anticipate any difficulties. Various commissions and committees were formed, notably the two Hyderabad commissions (1888 and 1890),^[132] to investigate the relative safety of chloroform. In the late 19th century, Hyderabad, a city in the middle of the Indian subcontinent, was the capital of the independent State of Hyderabad, ruled by the Nizam, Mir Mehboob Ali Khan.

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