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General Anesthetics

General anesthetics depress the central nervous system to a sufficient degree to permit the performance of surgery and other noxious or unpleasant procedures. Inevitably, anesthetics also suppress normal homeostatic reflexes. Not surprisingly, general anesthetics have low therapeutic indices and thus require great care in administration. While all general anesthetics produce a relatively similar anesthetic state, they are quite dissimilar in their secondary actions (side effects) on other organ systems. The selection of specific drugs and routes of administration to produce general anesthesia is based on their pharmacokinetic properties and on the secondary effects of the various drugs, in the context of the proposed diagnostic or surgical procedure and with the consideration of the individual patient's age, associated medical condition, and medication use. Anesthesiologists also employ sedatives (Chapter 17), neuromuscular blocking agents (Chapter 11), and local anesthetics (Chapter 20) as the situation requires.

Historical Perspectives. Crawford Long, a physician in rural Georgia, first used ether anesthesia in 1842. William T.G. Morton, a Boston dentist and medical student, performed the first public demonstration of general anesthesia using diethyl ether in 1846 when Gilbert Abbott underwent surgical excision of a neck tumor at the Massachusetts General Hospital in the operating room now known as "the ether dome." The era of modern anesthesia and a revolution in the medical care of the surgical patient had begun.

Ether was the ideal "first" anesthetic. A liquid at room temperature, it readily vaporized, and was easy to administer. Ether, unlike nitrous oxide, was potent and could produce anesthesia without diluting room air to hypoxic levels. It was relatively nontoxic and produced limited respiratory or circulatory compromise. Ether maintained a role in clinical anesthesia until the 1950s.

Horace Wells, a dentist, noted at a stage show that an injured participant under the influence of nitrous oxide felt no pain. The next day Wells had a tooth extracted while breathing nitrous oxide. An attempt in 1845 by Wells to demonstrate his discovery at the Massachusetts General Hospital in Boston ended in failure when the patient cried out and nitrous oxide fell into disuse. In 1868, Edmond Andrews, a Chicago surgeon, described the co-administration of nitrous oxide and oxygen, a practice that continues to this day.

The Scottish obstetrician James Simpson introduced chloroform in 1847. Chloroform had a more pleasant odor than ether and was nonflammable. It was, however, a hepatotoxin and a severe cardiovascular depressant, which limited its ultimate utility. Despite incidents of intraoperative and postoperative deaths associated with chloroform, its use continued, especially in Great Britain, for nearly 100 years.

The anesthetic properties of cyclopropane were discovered accidentally in 1929 by chemists analyzing impurities in propylene. Cyclopropane is a pleasant-smelling gas that produces rapid anesthetic induction and recovery, and was widely used as a general anesthetic for over 30 years. However, cyclopropane is explosive when mixed with air, oxygen, or nitrous oxide. In 1956 came the introduction of halothane, a ...

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