Discovery of Anesthesia is one of the most important advancement of modern medicine. The Renaissance saw significant advances in anatomy and surgical technique. However, despite all this progress, surgery remained a treatment of last resort. Largely because of the associated pain, many patients with surgical disorders chose certain death rather than undergo surgery. Although there has been a great deal of debate as to who deserves the most credit for the discovery of general anesthesia, it is generally agreed that certain scientific discoveries in the late 18th and early 19th centuries were critical to the eventual introduction and development of modern anesthetic techniques.

Although anesthesia is known since ancient times,  major advances occurred in the late 19th century, which together allowed the transition to modern surgery. An appreciation of the germ theory of disease led rapidly to the development and application of antiseptic techniques in surgery.

18^th century

Joseph Priestley (1733–1804) was an English polymath who discovered nitrous oxide, nitric oxide, ammonia, hydrogen chloride and  oxygen. Beginning in 1775, Priestley published his research in Experiments and Observations on Different Kinds of Air. The recent discoveries about these and other gases stimulated a great deal of interest in the European scientific community. Thomas Beddoes (1760–1808) was an physician and teacher of medicine. With an eye toward making further advances in this new science as well as offering treatment for diseases previously thought to be untreatable (such as asthma and tuberculosis), Beddoes founded the Pneumatic Institution for inhalation gas therapy in 1798 at Dowry Square in Clifton, Bristol.  Beddoes employed chemist and physicist Humphry Davy (1778–1829) as superintendent of the institute, and engineer James Watt (1736–1819) to help manufacture the gases.

During the course of his research at the Pneumatic Institution, Davy discovered the anesthetic properties of nitrous oxide. Davy, who coined the term “laughing gas” for nitrous oxide, published his findings the following year.  Davy was not a physician, and he never administered nitrous oxide during a surgical procedure. He was however the first to document the analgesic effects of nitrous oxide, as well as its potential benefits in relieving pain during surgery.

 

19^th century

 Eastern hemisphere

Hanaoka Seishu (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. 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. After years of research and experimentation, he finally developed a formula which he named tsūsensan . Like that of Hua Tuo, this compound was composed of extracts of several different plants.

The  five of these seven ingredients were thought to be elements of Hua Tuo’s anesthetic potion, used 1600 years earlier.

The active ingredients in tsūsensan are    scopolamine , hyoscyamine ,  atropine , aconitine , angelicotoxin.  In sufficient quantity, tsūsensan produces a state of general anesthesia and  skeletal muscle paralysis. 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.

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 anesthetic. This is generally regarded today as the first reliable documentation of an operation to be performed under general anesthesia. Hanaoka went on to perform many operations using tsūsensan, including resection of malignant masses,  extraction of bladder stones, and extremity amputations. Before his death in 1835, Hanaoka performed more than 150 operations for breast cancer.

Western hemisphere

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

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  of 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 north eastern 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. 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. 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. 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.

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 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. 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 parturition. Long however did not publish his experience until 1849, thereby denying himself much of the credit he deserved.

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.

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. 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. Robert Liston performed the first amputation in December of that year. Morton published his experience soon after  Harvard University professor Charles Thomas Jackson (1805–1880) later claimed that Morton stole his idea. Morton disagreed and a lifelong dispute began. 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.

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 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.

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.  All previous observations of the glottis and larynx (including those of Manuel García,  Wilhelm Hack 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.

 

https://en.wikipedia.org/wiki/History_of_general_anesthesia

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