History of general anesthesia

Opium poppy, Papaver somniferum

The Sumerians are said to have cultivated and harvested the opium poppy (Papaver somniferum) in lower Mesopotamia as early as 3400 BC,[7][8] though this has been disputed.[9] The most ancient testimony concerning the opium poppy found to date was inscribed in cuneiform script on a small white clay tablet at the end of the third millennium BC. This tablet was discovered in 1954 during excavations at Nippur, and is currently kept at the University of Pennsylvania Museum of Archaeology and Anthropology. Deciphered by Samuel Noah Kramer and Martin Leve, it is considered to be the most ancient pharmacopoeia in existence.[10][11] Some Sumerian tablets of this era have an ideogram inscribed upon them, "hul gil", which translates to "plant of joy", believed by some authors to refer to opium.[12][13] The term gil is still used for opium in certain parts of the world.[14] The Sumerian goddess Nidaba is often depicted with poppies growing out of her shoulders. About 2225 BC, the Sumerian territory became a part of the Babylonian empire. Knowledge and use of the opium poppy and its euphoric effects thus passed to the Babylonians, who expanded their empire eastwards to Persia and westwards to Egypt, thereby extending its range to these civilizations.[14] British archaeologist and cuneiformist Reginald Campbell Thompson writes that opium was known to the Assyrians in the 7th century BC.[15] The term "Arat Pa Pa" occurs in the Assyrian Herbal, a collection of inscribed Assyrian tablets dated to c. 650 BC. According to Thompson, this term is the Assyrian name for the juice of the poppy and it may be the etymological origin of the Latin "papaver".[12]

The ancient Egyptians had some surgical instruments,[16][17] as well as crude analgesics and sedatives, including possibly an extract prepared from the mandrake fruit.[18] The use of preparations similar to opium in surgery is recorded in the Ebers Papyrus, an Egyptian medical papyrus written in the Eighteenth Dynasty.[14][16][19] However, it is questionable whether opium itself was known in ancient Egypt.[20] The Greek gods Hypnos (Sleep), Nyx (Night), and Thanatos (Death) were often depicted holding poppies.[21]

Prior to the introduction of opium to ancient India and China, these civilizations pioneered the use of cannabis incense and aconitum. c. 400 BC, the Sushruta Samhita (a text from the Indian subcontinent on Ayurvedic medicine and surgery) advocates the use of wine with incense of cannabis for anesthesia.[22] By the 8th century AD, Arab traders had brought opium to India[23] and China.[24]

In Classical antiquity, anaesthetics were described by:

• Dioscorides (De Materia Medica)
• Galen
• Hippocrates
• Theophrastus (Historia Plantarum)

Hua Tuo, Chinese surgeon, c. AD 200

Bian Que (Chinese: 扁鵲, Wade–Giles: Pien Ch'iao, c. 300 BC) was a legendary Chinese internist and surgeon who reportedly used general anesthesia for surgical procedures. It is recorded in the Book of Master Han Fei (c. 250 BC), the Records of the Grand Historian (c. 100 BC), and the Book of Master Lie (c. 300 AD) that Bian Que gave two men, named "Lu" and "Chao", a toxic drink which rendered them unconscious for three days, during which time he performed a gastrostomy upon them.[25][26][27]

Hua Tuo (Chinese:華佗， c. 145–220 AD) was a Chinese surgeon of the 2nd century AD. According to the Records of Three Kingdoms (c. 270 AD) and the Book of the Later Han (c. 430 AD), Hua Tuo performed surgery under general anesthesia using a formula he had developed by mixing wine with a mixture of herbal extracts he called mafeisan (麻沸散).[28] Hua Tuo reportedly used mafeisan to perform even major operations such as resection of gangrenous intestines.[28][29][30] Before the surgery, he administered an oral anesthetic potion, probably dissolved in wine, in order to induce a state of unconsciousness and partial neuromuscular blockade.[28]

The exact composition of mafeisan, similar to all of Hua Tuo's clinical knowledge, was lost when he burned his manuscripts, just before his death.[31] The composition of the anesthetic powder was not mentioned in either the Records of Three Kingdoms or the Book of the Later Han. Because Confucian teachings regarded the body as sacred and surgery was considered a form of body mutilation, surgery was strongly discouraged in ancient China. Because of this, despite Hua Tuo's reported success with general anesthesia, the practice of surgery in ancient China ended with his death.[28]

The name mafeisan combines ma (麻, meaning "cannabis, hemp, numbed or tingling"), fei (沸, meaning "boiling or bubbling"), and san (散, meaning "to break up or scatter", or "medicine in powder form"). Therefore, the word mafeisan probably means something like "cannabis boil powder". Many sinologists and scholars of traditional Chinese medicine have guessed at the composition of Hua Tuo's mafeisan powder, but the exact components still remain unclear. His formula is believed to have contained some combination of:[28][31][32][33]

• bai zhi (Chinese:白芷，Angelica dahurica),
• cao wu (Chinese:草烏, Aconitum kusnezoffii, Aconitum kusnezoffii, Kusnezoff's monkshood, or wolfsbane root),
• chuān xiōng (Chinese:川芎，Ligusticum wallichii, or Szechuan lovage),
• dong quai (Chinese:当归, Angelica sinensis, or "female ginseng"),
• wu tou (烏頭, Aconitum carmichaelii, rhizome of Aconitum, or "Chinese monkshood"),
• yang jin hua (洋金花, Flos Daturae metelis, or Datura stramonium, jimson weed, devil's trumpet, thorn apple, locoweed, moonflower),
• ya pu lu (押不芦, Mandragora officinarum),
• rhododendron flower, and
• jasmine root.

Others have suggested the potion may have also contained hashish,[29] bhang,[30] shang-luh,[25] or opium.[34] Victor H. Mair wrote that mafei "appears to be a transcription of some Indo-European word related to "morphine"."[35] Some authors believe that Hua Tuo may have discovered surgical analgesia by acupuncture, and that mafeisan either had nothing to do with or was simply an adjunct to his strategy for anesthesia.[36] Many physicians have attempted to re-create the same formulation based on historical records but none have achieved the same clinical efficacy as Hua Tuo's. In any event, Hua Tuo's formula did not appear to be effective for major operations.[35][37]

Other substances used from antiquity for anesthetic purposes include extracts of juniper and coca.[38][39][40]

Takamine Tokumei from Shuri, Ryūkyū Kingdom, is reported to have made a general anesthesia in 1689 in the Ryukyus, now known as Okinawa. He passed on his knowledge to the Satsuma doctors in 1690 and to Ryūkyūan doctors in 1714.[53]

Hanaoka Seishū, a Japanese surgeon of the 18th and 19th centuries

Hanaoka Seishū (華岡 青洲, 1760–1835) of Osaka was a Japanese surgeon of the Edo period with a knowledge of Chinese herbal medicine, as well as Western surgical techniques he had learned through Rangaku (literally "Dutch learning", and by extension "Western learning"). Beginning in about 1785, Hanaoka embarked on a quest to re-create a compound that would have pharmacologic properties similar to Hua Tuo's mafeisan.[54] After years of research and experimentation, he finally developed a formula which he named tsūsensan (also known as mafutsu-san). Like that of Hua Tuo, this compound was composed of extracts of several different plants, including:[55][56][57]

• 2 parts bai zhi (Chinese:白芷，Angelica dahurica);
• 2 parts cao wu (Chinese:草烏，Aconitum sp., monkshood or wolfsbane);
• 2 parts chuān ban xia (Pinellia ternata);
• 2 parts chuān xiōng (Ligusticum wallichii, Cnidium rhizome, Cnidium officinale or Szechuan lovage);
• 2 parts dong quai (Angelica sinensis or female ginseng);
• 1 part tian nan xing (Arisaema rhizomatum or cobra lily)
• 8 parts yang jin hua (Datura stramonium, Korean morning glory, thorn apple, jimson weed, devil's trumpet, stinkweed, or locoweed).

The active ingredients in tsūsensan are scopolamine, hyoscyamine, atropine, aconitine and angelicotoxin. When consumed in sufficient quantity, tsūsensan produces a state of general anesthesia and skeletal muscle paralysis.[57] Shutei Nakagawa (1773–1850), a close friend of Hanaoka, wrote a small pamphlet titled "Mayaku-ko" ("narcotic powder") in 1796. Although the original manuscript was lost in a fire in 1867, this brochure described the current state of Hanaoka's research on general anesthesia.[58]

On 13 October 1804, Hanaoka performed a partial mastectomy for breast cancer on a 60-year-old woman named Kan Aiya, using tsūsensan as a general anaesthetic. This is generally regarded today as the first reliable documentation of an operation to be performed under general anesthesia.[54][56][59][60] Hanaoka went on to perform many operations using tsūsensan, including resection of malignant tumors, extraction of bladder stones, and extremity amputations. Before his death in 1835, Hanaoka performed more than 150 operations for breast cancer.[54][60][61][62]

Gardner Quincy Colton, 19th-century American dentist

Horace Wells, 19th-century American dentist

Crawford W. Long, 19th-century American physician

William T. G. Morton, 19th-century American dentist

Friedrich Sertürner (1783–1841) first isolated morphine from opium in 1804;[63] he named it morphine after Morpheus, the Greek god of dreams.[64][65]

Henry Hill Hickman (1800–1830) experimented with the use of carbon dioxide as an anesthetic in the 1820s. He would make the animal insensible, effectively via almost suffocating it with carbon dioxide, then determine the effects of the gas by amputating one of its limbs. In 1824, Hickman submitted the results of his research to the Royal Society in a short treatise titled Letter on suspended animation: with the view of ascertaining its probable utility in surgical operations on human subjects. The response was an 1826 article in The Lancet titled "Surgical Humbug" that ruthlessly criticised his work. Hickman died four years later at age 30. Though he was unappreciated at the time of his death, his work has since been positively reappraised and he is now recognised as one of the fathers of anesthesia.

By the late 1830s, Humphry Davy's experiments had become widely publicized within academic circles in the northeastern United States. Wandering lecturers would hold public gatherings, referred to as "ether frolics", where members of the audience were encouraged to inhale diethyl ether or nitrous oxide to demonstrate the mind-altering properties of these agents while providing much entertainment to onlookers.[66] Four notable men participated in these events and witnessed the use of ether in this manner. They were William Edward Clarke (1819–1898), Crawford W. Long (1815–1878), Horace Wells (1815–1848), and William T. G. Morton (1819–1868).

While attending undergraduate school in Rochester, New York, in 1839, classmates Clarke and Morton apparently participated in ether frolics with some regularity.[67][68][69][70] In January 1842, by now a medical student at Berkshire Medical College, Clarke administered ether to a Miss Hobbie, while Elijah Pope performed a dental extraction.[68] In so doing, he became the first to administer an inhaled anesthetic to facilitate the performance of a surgical procedure. Clarke apparently thought little of his accomplishment, and chose neither to publish nor to pursue this technique any further. Indeed, this event is not even mentioned in Clarke's biography.[71]

Crawford W. Long was a physician and pharmacist practicing in Jefferson, Georgia in the mid-19th century. During his time as a student at the University of Pennsylvania School of Medicine in the late 1830s, he had observed and probably participated in the ether frolics that had become popular at that time. At these gatherings, Long observed that some participants experienced bumps and bruises, but afterward had no recall of what had happened. He postulated that diethyl ether produced pharmacologic effects similar to those of nitrous oxide. On 30 March 1842, he administered diethyl ether by inhalation to a man named James Venable, in order to remove a tumor from the man's neck.[72] Long later removed a second tumor from Venable, again under ether anesthesia. He went on to employ ether as a general anesthetic for limb amputations and childbirth. Long, however, did not publish his experience until 1849, thereby denying himself much of the credit he deserved.[72]

With the beginnings of modern medicine the stage was set for physicians and surgeons to build a paradigm in which anesthesia became useful.[73]

On 10 December 1844, Gardner Quincy Colton held a public demonstration of nitrous oxide in Hartford, Connecticut. One of the participants, Samuel A. Cooley, sustained a significant injury to his leg while under the influence of nitrous oxide without noticing the injury. Horace Wells, a Connecticut dentist present in the audience that day, immediately seized upon the significance of this apparent analgesic effect of nitrous oxide. The following day, Wells underwent a painless dental extraction while under the influence of nitrous oxide administered by Colton. Wells then began to administer nitrous oxide to his patients, successfully performing several dental extractions over the next couple of weeks.

William T. G. Morton, another New England dentist, was a former student and then-current business partner of Wells. He was also a former acquaintance and classmate of William Edward Clarke (the two had attended undergraduate school together in Rochester, New York). Morton arranged for Wells to demonstrate his technique for dental extraction under nitrous oxide general anesthesia at Massachusetts General Hospital, in conjunction with the prominent surgeon John Collins Warren. This demonstration, which took place on 20 January 1845, ended in failure when the patient cried out in pain in the middle of the operation.[74]

On 30 September 1846, Morton administered diethyl ether to Eben Frost, a music teacher from Boston, for a dental extraction. Two weeks later, Morton became the first to publicly demonstrate the use of diethyl ether as a general anesthetic at Massachusetts General Hospital, in what is known today as the Ether Dome.[75] On 16 October 1846, John Collins Warren removed a tumor from the neck of a local printer, Edward Gilbert Abbott. Upon completion of the procedure, Warren reportedly quipped, "Gentlemen, this is no humbug." News of this event rapidly traveled around the world.[76] Robert Liston performed the first amputation in December of that year. Morton published his experience soon after.[75] Harvard University professor Charles Thomas Jackson (1805–1880) later claimed that Morton stole his idea;[77] Morton disagreed and a lifelong dispute began.[76] For many years, Morton was credited as being the pioneer of general anesthesia in the Western hemisphere, despite the fact that his demonstration occurred four years after Long's initial experience. Long later petitioned William Crosby Dawson (1798–1856), a United States Senator from Georgia at that time, to support his claim on the floor of the United States Senate as the first to use ether anesthesia.[78]

In 1847, Scottish obstetrician James Young Simpson (1811–1870) of Edinburgh was the first to use chloroform as a general anesthetic on a human (Robert Mortimer Glover had written on this possibility in 1842 but only used it on dogs). The use of chloroform anesthesia expanded rapidly thereafter in Europe. Chloroform began to replace ether as an anesthetic in the United States at the beginning of the 20th century. It was soon abandoned in favor of ether when its hepatic and cardiac toxicity, especially its tendency to cause potentially fatal cardiac dysrhythmias, became apparent. In fact, the use of chloroform versus ether as the primary anesthetic gas varied by country and region. For instance, Britain and the American South stuck with chloroform while the American North returned to ether.[73] John Snow quickly became the most experienced British physician working with the new anesthetic gases of ether and chloroform thus becoming, in effect, the first British anesthetist. Through his careful clinical records he was eventually able to convince the elite of London medicine that anesthesia (chloroform) had a rightful place in childbirth. Thus, in 1853 Queen Victoria's accoucheurs invited John Snow to anesthetize the Queen for the birth of her eighth child.[79] From the beginnings of ether and chloroform anesthesia until well into the 20th century, the standard method of administration was the drop mask. A mask was placed over the patient's mouth with some fabric in it and the volatile liquid was dropped onto the mask with the patient spontaneously breathing. Later development of safe endotracheal tubes changed this.[80] Because of the unique social setting of London medicine, anesthesia had become its own speciality there by the end of the nineteenth century, while in the rest of the United Kingdom and most of the world anesthesia remained under the purview of the surgeon who would assign the task to a junior doctor or nurse.[73]

After Austrian diplomat Karl von Scherzer brought back sufficient quantities of coca leaves from Peru, in 1860 Albert Niemann isolated cocaine, which thus became the first local anesthetic.[81][82]

In 1871, the German surgeon Friedrich Trendelenburg (1844–1924) published a paper describing the first successful elective human tracheotomy to be performed for the purpose of administration of general anesthesia.[83][84][85][86]

In 1880, the Scottish surgeon William Macewen (1848–1924) reported on his use of orotracheal intubation as an alternative to tracheotomy to allow a patient with glottic edema to breathe, as well as in the setting of general anesthesia with chloroform.[87][88][89] All previous observations of the glottis and larynx (including those of Manuel García,[90] Wilhelm Hack[91][92] and Macewen) had been performed under indirect vision (using mirrors) until 23 April 1895, when Alfred Kirstein (1863–1922) of Germany first described direct visualization of the vocal cords. Kirstein performed the first direct laryngoscopy in Berlin, using an esophagoscope he had modified for this purpose; he called this device an autoscope.[93] The death of Emperor Frederick III (1831–1888)[94] may have motivated Kirstein to develop the autoscope.[95]