The specialty of anesthesia began in the mid-nineteenth century and became firmly established less than six decades ago. Ancient civilizations had used opium poppy, coca leaves, mandrake root, alcohol, and even phlebotomy (to the point of unconsciousness) to allow surgeons to operate. Ancient Egyptians used the combination of opium poppy (containing morphine) and hyoscyamus (containing scopolamine); a similar combination, morphine and scopolamine, has been used parenterally for premedication. What passed for regional anesthesia in ancient times consisted of compression of nerve trunks (nerve ischemia) or the application of cold (cryoanalgesia). The Incas may have practiced local anesthesia as their surgeons chewed coca leaves and applied them to operative wounds, particularly prior to trephining for headache.
The evolution of modern surgery was hampered not only by a poor understanding of disease processes, anatomy, and surgical asepsis but also by the lack of reliable and safe anesthetic techniques. These techniques evolved first with inhalation anesthesia, followed by local and regional anesthesia, and finally intravenous anesthesia. The development of surgical anesthesia is considered one of the most important discoveries in human history.
Because the hypodermic needle was not invented until 1855, the first general anesthetics were destined to be inhalation agents. Diethyl ether (known at the time as “sulfuric ether” because it was produced by a simple chemical reaction between ethyl alcohol and sulfuric acid) was originally prepared in 1540 by Valerius Cordus.
Ether was used for frivolous purposes (“ether frolics”), but not as an anesthetic agent in humans until 1842, when Crawford W. Long and William E. Clark independently used it on patients for surgery and dental extraction, respectively. However, they did not publicize their discovery. Four years later, in Boston, on October 16, 1846, William T.G. Morton conducted the first publicized demonstration of general anesthesia for surgical operation using ether. The dramatic success of that exhibition led the operating surgeon to exclaim to a skeptical audience: “Gentlemen, this is no humbug!”
Chloroform was independently prepared by von Leibig, Guthrie, and Soubeiran in 1831. Although first used by Holmes Coote in 1847, chloroform was introduced into clinical practice by the Scot Sir James Simpson, who administered it to his patients to relieve the pain of labor. Ironically, Simpson had almost abandoned his medical practice after witnessing the terrible despair and agony of patients undergoing operations without anesthesia.
Joseph Priestley produced nitrous oxide in 1772, and Humphry Davy first noted its analgesic properties in 1800. Gardner Colton and Horace Wells are credited with having first used nitrous oxide as an anesthetic for dental extractions in humans in 1844. Nitrous oxide’s lack of potency (an 80% nitrous oxide concentration results in analgesia but not surgical anesthesia) led to clinical demonstrations that were less convincing than those with ether.
Nitrous oxide was the least popular of the three early inhalation anesthetics because of its low potency and its tendency to cause asphyxia when used alone (see Chapter 8). Interest in nitrous oxide was revived in 1868 when Edmund Andrews administered it in 20% oxygen; its use was, however, overshadowed by the popularity of ether and chloroform. Ironically, nitrous oxide is the only one of these three agents still in widespread use today. Chloroform superseded ether in popularity in many areas (particularly in the United Kingdom), but reports of chloroform-related cardiac arrhythmias, respiratory depression, and hepatotoxicity eventually caused practitioners to abandon it in favor of ether, particularly in North America.
Even after the introduction of other inhalation anesthetics (ethyl chloride, ethylene, divinyl ether, cyclopropane, trichloroethylene, and fluroxene), ether remained the standard inhaled anesthetic until the early 1960s. The only inhalation agent that rivaled ether’s safety and popularity was cyclopropane (introduced in 1934). However, both are highly combustible and both have since been replaced by a succession of nonflammable potent fluorinated hydrocarbons: halothane (developed in 1951; released in 1956), methoxyflurane (developed in 1958; released in 1960), enflurane (developed in 1963; released in 1973), and isoflurane (developed in 1965; released in 1981).
Two newer agents are now the most popular in developed countries. Desflurane (released in 1992), has many of the desirable properties of isoflurane as well as more rapid uptake and elimination (nearly as fast as nitrous oxide). Sevoflurane, has low blood solubility, but concerns about the potential toxicity of its degradation products delayed its release in the United States until 1994 (see Chapter 8). These concerns have proved to be largely theoretical, and sevoflurane, not desflurane, has become the most widely used inhaled anesthetic in the United States, largely replacing halothane in pediatric practice.
Local & Regional Anesthesia
The medicinal qualities of coca had been used by the Incas for centuries before its actions were first observed by Europeans. Cocaine was isolated from coca leaves in 1855 by Gaedicke and was purified in 1860 by Albert Niemann.
The original application of modern local anesthesia is credited to Carl Koller, at the time a house officer in ophthalmology, who demonstrated topical anesthesia of the eye with cocaine
in 1884. Later in 1884 William Halsted used cocaine
for intradermal infiltration and nerve blocks (including blocks of the facial nerve, brachial plexus, pudendal nerve, and posterior tibial nerve). August Bier is credited with administering the first spinal anesthetic in 1898. He was also the first to describe intravenous regional anesthesia (Bier block) in 1908. Procaine was synthesized in 1904 by Alfred Einhorn and within a year was used clinically as a local anesthetic by Heinrich Braun. Braun was also the first to add epinephrine
to prolong the duration of local anesthetics. Ferdinand Cathelin and Jean Sicard introduced caudal epidural anesthesia in 1901. Lumbar epidural anesthesia was described first in 1921 by Fidel Pages and again (independently) in 1931 by Achille Dogliotti. Additional local anesthetics subsequently introduced include dibucaine
(1963), and etidocaine (1972). The most recent additions, ropivacaine
and levobupivacaine, have durations of action similar to bupivacaine
but less cardiac toxicity (see Chapter 16).
Intravenous anesthesia required the invention of the hypodermic syringe and needle by Alexander Wood in 1855. Early attempts at intravenous anesthesia included the use of chloral hydrate (by Oré in 1872), chloroform and ether (Burkhardt in 1909), and the combination of morphine and scopolamine (Bredenfeld in 1916). Barbiturates were first synthesized in 1903 by Fischer and von Mering. The first barbiturate used for induction of anesthesia was diethylbarbituric acid (barbital), but it was not until the introduction of hexobarbital in 1927 that barbiturate induction became popular. Thiopental, synthesized in 1932 by Volwiler and Tabern, was first used clinically by John Lundy and Ralph Waters in 1934 and for many years remained the most common agent for intravenous induction of anesthesia. Methohexital was first used clinically in 1957 by V. K. Stoelting and is the only other barbiturate used for induction of anesthesia in humans. After chlordiazepoxide was discovered in 1955 and released for clinical use in 1960, other benzodiazepines—diazepam, lorazepam, and midazolam—came to be used extensively for premedication, conscious sedation, and induction of general anesthesia. Ketamine was synthesized in 1962 by Stevens and first used clinically in 1965 by Corssen and Domino; it was released in 1970 and continues to be popular today, particular when administered in combination with other agents. Etomidate was synthesized in 1964 and released in 1972. Initial enthusiasm over its relative lack of circulatory and respiratory effects was tempered by evidence of adrenal suppression, reported after even a single dose. The release of propofol in 1986 (1989 in the United States) was a major advance in outpatient anesthesia because of its short duration of action (see Chapter 9). Propofol is currently the most popular agent for intravenous induction worldwide.
Neuromuscular Blocking Agents
The introduction of curare by Harold Griffith and Enid Johnson in 1942 was a milestone in anesthesia.
Curare greatly facilitated tracheal intubation and muscle relaxation during surgery. For the first time, operations could be performed on patients without the requirement that relatively deep levels of inhaled general anesthetic be used to produce muscle relaxation. Such large doses of anesthetic often resulted in excessive cardiovascular and respiratory depression as well as prolonged emergence. Moreover, larger doses were often not tolerated by frail patients.
Succinylcholine was synthesized by Bovet in 1949 and released in 1951; it has become a standard agent for facilitating tracheal intubation during rapid sequence induction. Until recently, succinylcholine remained unchallenged in its rapid onset of profound muscle relaxation, but its side effects prompted the search for a comparable substitute. Other neuromuscular blockers (NMBs; discussed in Chapter 11)—gallamine, decamethonium, metocurine, alcuronium, and pancuronium—were subsequently introduced. Unfortunately, these agents were often associated with side effects (see Chapter 11), and the search for the ideal NMB continued. Recently introduced agents that more closely resemble an ideal NMB include vecuronium, atracurium, rocuronium, and cis-atracurium.
Morphine, isolated from opium in 1805 by Sertürner, was also tried as an intravenous anesthetic. The adverse events associated with large doses of opioids in early reports caused many anesthetists to avoid opioids and favor pure inhalation anesthesia. Interest in opioids in anesthesia returned following the synthesis and introduction of meperidine in 1939. The concept of balanced anesthesia was introduced in 1926 by Lundy and others and evolved to include thiopental for induction, nitrous oxide for amnesia, an opioid for analgesia, and curare for muscle relaxation. In 1969, Lowenstein rekindled interest in “pure” opioid anesthesia by reintroducing the concept of large doses of opioids as complete anesthetics. Morphine was the first agent so employed, but fentanyl and sufentanil have been preferred by a large margin as sole agents. As experience grew with this technique, its multiple limitations—unreliably preventing patient awareness, incompletely suppressing autonomic responses during surgery, and prolonged respiratory depression—were realized. Remifentanil, an opioid subject to rapid degradation by nonspecific plasma and tissue esterases, permits profound levels of opioid analgesia to be employed without concerns regarding the need for postoperative ventilation.
Evolution of the Specialty
Following its first public demonstration in the United States, ether anesthesia quickly was adopted in England.
John Snow, often considered the father of the anesthesia specialty, was the first physician to take a full-time interest in this new anesthetic. He was the first to scientifically investigate ether and the physiology of general anesthesia. Of course, Snow was also a pioneer in epidemiology. He helped stop a cholera epidemic in London by proving that the causative agent was transmitted by ingestion of contaminated well water rather than by inhalation. In 1847, Snow published the first book on general anesthesia, On the Inhalation of Ether
. When the anesthetic properties of chloroform were made known, he quickly investigated and developed an inhaler for that agent as well. He believed that an inhaler should be used in administering ether or chloroform to control the dose of the anesthetic. His second book, On Chloroform and Other Anaesthetics
, was published posthumously in 1858.
After Snow’s death, Dr. Joseph T. Clover took his place as England’s leading anesthetist. Clover emphasized continuously monitoring the patient’s pulse during anesthesia, a practice that was not yet standard at the time. He was the first to use the jaw-thrust maneuver for relieving airway obstruction, the first to insist that resuscitation equipment always be available during anesthesia, and the first to use a cricothyroid cannula (to save a patient with an oral tumor who developed complete airway obstruction). After Clover, Sir Frederic Hewitt became England’s foremost anesthetist at the turn of the last century. He was responsible for many inventions, including the oral airway. Hewitt also wrote what many consider to be the first true textbook of anesthesia, which went through five editions. Snow, Clover, and Hewitt established the tradition of physician anesthetists in England. In 1893, the first organization of physician specialists in anesthesia, the London Society of Anaesthetists, was formed in England by J.F. Silk.
The first elective tracheal intubations during anesthesia were performed in the late nineteenth century by surgeons Sir William MacEwen in Scotland, Joseph O’Dwyer in the United States, and Franz Kuhn in Germany. Tracheal intubation during anesthesia was popularized in England by Sir Ivan Magill and Stanley Rowbotham in the 1920s.
In the United States, only a few physicians had specialized in anesthesia by 1900. The task of providing general anesthesia was often delegated to junior surgical house officers or medical students, if they were available.
The first organization of physician anesthetists in the United States was the Long Island Society of Anesthetists formed in 1905, which, as it grew, was renamed the New York Society of Anesthetists in 1911. The International Anesthesia Research Society (IARS) was founded in 1922, and in that same year the IARS-sponsored scientific journal Current Researches in Anesthesia and Analgesia (now called Anesthesia and Analgesia) began publication. In 1936, the New York Society of Anesthetists became the American Society of Anesthetists, and later, in 1945, the American Society of Anesthesiologists (ASA). The scientific journal Anesthesiology was first published in 1940.
Four physicians stand out in the early development of anesthesia in the United States after 1900: F.H. McMechan, Arthur E. Guedel, Ralph M. Waters, and John S. Lundy. McMechan was the driving force behind both the IARS and Current Researches in Anesthesia and Analgesia, and tirelessly organized physicians specializing in anesthesia into national and international organizations until his death in 1939. Guedel was the first to describe the signs and stages of general anesthesia. He advocated cuffed tracheal tubes and introduced artificial ventilation during ether anesthesia (later termed controlled respiration by Waters). Ralph Waters made a long list of contributions to the specialty, probably the most important of which was his insistence on the proper education of specialists in anesthesia. Waters developed the first academic department of anesthesiology at the University of Wisconsin in Madison. Lundy was instrumental in the formation of the American Board of Anesthesiology and chaired the American Medical Association’s Section on Anesthesiology for 17 years.
Because of the scarcity of physicians specializing in anesthesia in the United States and the perceived relative safety of ether anesthesia, surgeons at both the Mayo Clinic and Cleveland Clinic began training and employing nurses as anesthetists in the early 1900s. As the numbers of nurse anesthetists increased, a national organization (now called the American Association of Nurse Anesthetists) was incorporated in 1932. The AANA first offered a certification examination in 1945. In 1969 two Anesthesiology Assistant programs began accepting students, and in 1989 the first certification examinations for AAs were administered. Certified Registered Nurse Anesthetists and Anesthesiologist Assistants represent important members of the anesthesia workforce in the United States and in other countries.
In 1889 Henry Isaiah Dorr, a dentist, was appointed Professor of the Practice of Dentistry, Anaesthetics and Anaesthesia at the Philadelphia College of Dentistry. Thus he was the first known professor of anesthesia worldwide. Thomas D. Buchanan, of the New York Medical College, was the first physician to be appointed Professor of Anesthesia (in 1905). When the American Board of Anesthesiology was established in 1938, Dr. Buchanan served as its first president. In England, the first examination for the Diploma in Anaesthetics took place in 1935, and the first Chair in Anaesthetics was awarded to Sir Robert Macintosh in 1937 at Oxford University. Anesthesia became an officially recognized specialty in England only in 1947, when the Royal College of Surgeons established its Faculty of Anaesthetists. In 1992 an independent Royal College of Anaesthetists was granted its charter.