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[[File:Southworth & Hawes - First etherized operation (re-enactment).jpg|thumb|Re-enactment of the first public demonstration of [[general anesthesia]] by [[William T. G. Morton]] on October 16, 1846, in the [[Ether Dome]] at [[Massachusetts General Hospital]], [[Boston]]. Surgeons [[John Collins Warren]] and [[Henry Jacob Bigelow]] are included in this [[daguerrotype]] by [[Southworth & Hawes]].]]
[[File:Bulfinch Building.jpg|thumb|The [[Charles Bulfinch|Bulfinch]] Building, home of the [[Ether Dome]]]]

Throughout [[recorded history]], attempts at producing a state of [[general anesthesia]] can be traced back to the writings of ancient [[Sumerians]], [[Babylonians]], [[Assyrian people|Assyrians]], [[ancient Egyptians|Egyptians]], [[Indus Valley Civilization|Indians]], and [[history of China#Ancient China|Chinese]]. Despite significant advances in [[anatomy]] and [[surgical technique]] during the [[Renaissance]], surgery remained a last-resort treatment largely due to the [[pain]] associated with it. However, scientific discoveries in the late 18th and early 19th centuries paved the way for the development of modern anesthetic techniques.{{citation needed|date=February 2022}}

In the late 19th century, two major advances enabled the transition to modern surgery: the development and application of [[antiseptic]] techniques as a result of the [[germ theory of disease]], which reduced [[morbidity]] and [[mortality rate]]s, and the advances in [[pharmacology]] and [[physiology]] that led to the development of general anesthesia and pain control. In the 20th century, general anesthesia's safety and efficacy were further improved with the routine use of [[tracheal intubation]] and [[advanced airway management]] techniques, [[monitoring (medicine)|monitoring]], and new [[anesthetic agent]]s with improved characteristics. Standardized training programs for [[anesthesiologist]]s and [[nurse anesthetist]]s emerged during this period.

Moreover, the application of economic and business administration principles to healthcare in the late 20th and early 21st centuries led to the introduction of management practices, such as [[transfer pricing]], to improve the efficiency of anesthetists.<ref name="kuntz2005">{{cite journal |last1=Kuntz |first1=L |last2=Vera |first2=A |title=Transfer pricing in hospitals and efficiency of physicians: the case of anesthesia services |journal=Health Care Management Review |volume=30 |issue=3 |date=July–September 2005 |pages=262–69 |pmid=16093892 |s2cid=33859170 |doi=10.1097/00004010-200507000-00010}}</ref>

==Etymology of ''anesthesia''==

In [[Ancient Greek]] texts, including the [[Hippocratic Corpus]], [[Timaeus (dialogue)|Timaeus]], and others, the term {{wikt-lang|grc|ἀναισθησίᾱ|italic=no}} (''anaisthēsíā'', "without sensation") is attested; from {{lang|grc|ἀν-}} (''an-'', "without") and {{lang|grc|αἴσθησις}} (''aisthēsis'', "[[sensation (psychology)|sensation]]").<ref name=haridas>{{cite journal |last1=Haridas |first1=Rajesh P. |title=Earliest English Definitions of ''Anaisthesia'' and ''Anaesthesia'' |journal=Anesthesiology |volume=127 |issue=5 |date=1 November 2017 |pages=747–753 |pmid=28654424 |s2cid=33004661 |doi=10.1097/ALN.0000000000001764}}</ref><ref>{{LSJ|a)naisqhsi/a|ἀναισθησία|ref}}</ref>

In 1679, [[Steven Blankaart]] publishes ''Lexicon medicum graeco-latinum'' with the Latin term ''anaisthesia''. In 1684, an English translation appears titled ''A Physical Dictionary'', with ''anaisthesia'' defined as "defect of sensation, as in paralytic and blasted persons". Subsequently, the term and variant spellings like ''anæsthesia'' are used in medical literature signifying "insensibility".{{r|haridas}}

In 1846, in a letter, [[Oliver Wendell Holmes Sr.|Oliver Wendell Holmes]] proposes the term ''anesthesia'' to be used for the state induced by an agent and ''anesthetic'' for the agent itself. Holmes motivates this with earlier uses of anesthesia in medical literature to mean "insensibility", particularly to "objects of touch".<ref name="Small1962"/><ref>{{cite journal |last1=Haridas |first1=R. P. |title=The etymology and Use of the Word 'Anaesthesia': Oliver Wendell Holmes' Letter to W. T. G. Morton |journal=Anaesthesia and Intensive Care |volume=44 |date=July 2016 |pages=38–44 |pmid=27456290 |doi=10.1177/0310057X1604401S07 |doi-access=free}}</ref>{{r|haridas}}

==Antiquity==
The first attempts at general anesthesia were probably [[herbalism|herbal remedies]] administered in [[prehistory]]. [[Ethanol|Alcohol]] is the oldest known [[sedative]]; it was used in ancient [[Mesopotamia]] thousands of years ago.<ref name="Powell1996"/>

===Opium===
[[File:Illustration Papaver somniferum0.jpg|thumb|upright|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,<ref name="Neligan1927"/><ref name="Booth1996"/> though this has been disputed.<ref name="Krikorian1975"/> 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.<ref name="Kramer1954"/><ref name="Kramer1988 "/> 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.<ref name="Terry1928"/><ref name="Sonnedecker1962"/> The term ''gil'' is still used for opium in certain parts of the world.<ref name="Anslinger1953"/> 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 [[euphoria|euphoric]] effects thus passed to the Babylonians, who expanded their empire eastwards to [[Iran|Persia]] and westwards to Egypt, thereby extending its range to these civilizations.<ref name="Anslinger1953"/> British archaeologist and cuneiformist [[Reginald Campbell Thompson]] writes that opium was known to the Assyrians in the 7th century BC.<ref name="Thomson1924"/> 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 [[etymology|etymological]] origin of the Latin "''[[papaver]]''".<ref name="Terry1928"/>

The ancient Egyptians had some surgical instruments,<ref name="Ebers1889"/><ref name="Pahor1992I"/> as well as crude analgesics and sedatives, including possibly an extract prepared from the [[mandrake (plant)|mandrake]] fruit.<ref name="Sullivan1996"/> The use of preparations similar to opium in surgery is recorded in the [[Ebers Papyrus]], an [[Egyptian medical papyri|Egyptian medical papyrus]] written in the [[Eighteenth Dynasty of Egypt|Eighteenth Dynasty]].<ref name="Anslinger1953"/><ref name="Ebers1889"/><ref name="Ebbell1937"/> However, it is questionable whether opium itself was known in ancient Egypt.<ref name="Bisset1994"/> The Greek gods [[Hypnos]] (Sleep), [[Nyx]] (Night), and [[Thanatos]] (Death) were often depicted holding poppies.<ref name="Kritikos1967-3"/>

Prior to the introduction of opium to [[Indus Valley Civilization|ancient India]] and [[history of China#Ancient China|China]], these civilizations pioneered the use of [[cannabis (drug)|cannabis]] [[incense]] and [[aconitum]]. c. 400 BC, the [[Sushruta Samhita]] (a text from the [[Indian subcontinent]] on [[Ayurveda|Ayurvedic medicine]] and surgery) advocates the use of [[wine]] with incense of cannabis for anesthesia.<ref name="Sushruta"/> By the 8th century AD, Arab traders had brought opium to India<ref name="Dwarakanath1965"/> and China.<ref name="Fort1965"/>

===Classical antiquity===
{{Expand section|date=February 2015}}

In [[Classical antiquity]], anaesthetics were described by:

* Pedanius [[Pedanius Dioscorides|Dioscorides]] (''[[De Materia Medica]]''), a Greek physician living in Rome during the first century A.D., who is recorded as the first person to make explicit reference to the administration of mandrake-induced anesthesia to facilitate a surgical intervention.<ref>{{Cite journal |last1=Doufas |first1=Anthony G. |last2=Saidman |first2=Lawrence J. |date=January 2010 |title=The Hippocratic Paradigm in Medicine: Origins of the Clinical Encounter |url=https://journals.lww.com/anesthesia-analgesia/Fulltext/2010/01000/The_Hippocratic_Paradigm_in_Medicine__Origins_of.2.aspx |journal=Anesthesia & Analgesia |language=en-US |volume=110 |issue=1 |pages=4–6 |doi=10.1213/ANE.0b013e3181c0f223 |pmid=20023180 |issn=0003-2999}}</ref>
* [[Galen]]
* [[Hippocrates]]
* [[Theophrastus]] (''[[Historia Plantarum (Theophrastus)|Historia Plantarum]]'')

===China and Hua Tuo's ancient chemical mixture===
[[File:HuaTuo.jpg|thumb|upright|[[Hua Tuo]], Chinese [[surgeon]], c. AD 200]]

[[Bian Que]] ([[Chinese character|Chinese]]: 扁鵲, [[Wade–Giles]]: ''Pien Ch'iao'', {{circa|300 BC}}) was a legendary Chinese [[internal medicine|internist]] and surgeon who reportedly used general anesthesia for surgical procedures. It is recorded in the ''[[Han Feizi (book)|Book of Master Han Fei]]'' ({{circa|250 BC}}), the ''[[Records of the Grand Historian]]'' ({{circa|100 BC}}), and the ''[[Liezi|Book of Master Lie]]'' ({{circa|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.<ref name="Gordon1949"/><ref name="Giles1912"/><ref name="Salguero2009"/>

[[Hua Tuo]] ([[Chinese character|Chinese]]:華佗， {{circa|145–220 AD}}) was a Chinese [[surgeon]] of the 2nd century AD. According to the ''[[Records of Three Kingdoms]]'' ({{circa|270 AD}}) and the ''[[Book of the Later Han]]'' ({{circa|430 AD}}), Hua Tuo performed surgery under general anesthesia using a formula he had developed by mixing wine with a mixture of [[herbal extract]]s he called ''[[Hua Tuo#Mafeisan|mafeisan]]'' (麻沸散).<ref name="Chu2004"/> Hua Tuo reportedly used mafeisan to perform even major operations such as [[segmental resection|resection]] of [[gangrene|gangrenous]] [[intestines]].<ref name="Chu2004"/><ref name="Giles1897"/><ref name="Giles1948"/> Before the surgery, he administered an oral anesthetic [[potion]], probably dissolved in wine, in order to induce a state of [[unconsciousness]] and partial [[neuromuscular-blocking drug|neuromuscular blockade]].<ref name="Chu2004"/>

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.<ref name="Chen2008"/> The composition of the anesthetic powder was not mentioned in either the ''Records of Three Kingdoms'' or the ''Book of the Later Han''. Because [[Confucianism|Confucian]] teachings regarded the body as [[sacred]] and surgery was considered a form of body mutilation, surgery was strongly discouraged in [[history of China#Ancient China|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.<ref name="Chu2004"/>

The name ''mafeisan'' combines ''ma'' ([[Wikt:麻|麻]], meaning "cannabis, [[hemp]], [[Anesthesia|numbed]] or [[Paresthesia|tingling]]"), ''fei'' ([[Wikt:沸|沸]], meaning "[[boiling]] or bubbling"), and ''san'' ([[Wikt:散|散]], meaning "to break up or scatter", or "medicine in powder form"). Therefore, the word ''mafeisan'' probably means something like "cannabis boil powder". Many [[sinology|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:<ref name="Chu2004"/><ref name="Chen2008"/><ref name="Wang1999"/><ref name="Fu2002"/>

* ''bai zhi'' (''[[Chinese character|Chinese]]:白芷''，''[[Angelica|Angelica dahurica]]''),
* ''cao wu'' (''[[Chinese character|Chinese]]:草烏'', ''[[species:Aconitum kusnezoffii|Aconitum kusnezoffii]]'', ''[[Aconitum|Aconitum kusnezoffii]]'', Kusnezoff's monkshood, or wolfsbane root),
* ''chuān xiōng'' (''[[Chinese character|Chinese]]:川芎，[[Ligusticum wallichii]]'', or Szechuan lovage),
* ''dong quai'' (''[[Chinese character|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, ''[[species:Datura metel|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]],<ref name="Giles1897"/> [[bhang]],<ref name="Giles1948"/> ''shang-luh'',<ref name="Gordon1949"/> or opium.<ref name="Veith1972"/> [[Victor H. Mair]] wrote that ''mafei'' "appears to be a transcription of some [[Indo-European languages|Indo-European]] word related to "morphine"."<ref name="Mair2000"/> 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.<ref name="Lu2002"/> 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.<ref name="Mair2000"/><ref name="Wai2004"/>

Other substances used from antiquity for anesthetic purposes include extracts of [[juniper]] and [[coca]].<ref name="Carroll"/><ref name="Peterson"/><ref name="Rivera"/>

==Middle Ages and Renaissance==
[[Ferdowsi]] (940–1020) was a [[Persian people|Persian]] [[poet]] who lived in the [[Abbasid Caliphate]]. In ''[[Shahnameh]]'', his [[national epic]] poem, Ferdowsi described a [[caesarean section]] performed on [[Rudaba]].{{citation needed|date=September 2010}} A special wine prepared by a [[Zoroastrianism|Zoroastrian]] priest was used as an anesthetic for this operation.<ref name="Gordon1949"/>

Circa 1020, [[Avicenna|Ibn Sīnā]] (980–1037) in ''[[The Canon of Medicine]]'' described the "soporific sponge", a [[sponge (material)|sponge]] imbued with [[aroma compound|aromatics]] and [[narcotic]]s, which was to be placed under a patient's nose during surgical operations.<ref name="Skinner2008"/><ref name="Ajram1992"/><ref name="Hunke1969"/> Opium made its way from Asia Minor to all parts of Europe between the 10th and 13th centuries.<ref name="Kritikos1967-2"/>

Throughout 1200 to 1500 AD in England, a potion called [[dwale (anaesthetic)|dwale]] was used as an anesthetic.<ref name="ncbi.nlm.nih.gov">{{cite journal |last=Carter |first=Anthony J. |title=Dwale: an anaesthetic from old England |journal=[[BMJ]] |volume=319 |issue=7225 |date=18 December 1999 |pages=1623–1626 |pmc=1127089 |pmid=10600971 |doi=10.1136/bmj.319.7225.1623}}</ref> This [[ethanol|alcohol]]-based mixture contained [[bile]], [[opium]], [[lettuce]], [[bryony]], [[henbane]], [[conium|hemlock]], and [[vinegar]].<ref name="ncbi.nlm.nih.gov"/> Surgeons roused their patients by rubbing vinegar and salt on their cheekbones.<ref name="ncbi.nlm.nih.gov"/> One can find records of dwale in numerous literary sources, including [[Shakespeare's]] ''[[Hamlet]]'', and the [[John Keats]] poem "[[Ode to a Nightingale]]".<ref name="ncbi.nlm.nih.gov"/> In the 13th century, we have the first prescription of the "spongia soporifica"—a sponge soaked in the juices of unripe mulberry, flax, mandragora leaves, ivy, lettuce seeds, lapathum, and hemlock with hyoscyamus. After treatment and/or storage, the sponge could be heated and the vapors inhaled with anesthetic effect.{{citation needed|date=February 2015}}

[[Alchemy|Alchemist]] [[Ramon Llull]] has been credited with discovering [[diethyl ether]] in 1275.{{citation needed|date=September 2010}} <ref name="ncbi.nlm.nih.gov"/> Aureolus Theophrastus Bombastus von Hohenheim (1493–1541), better known as [[Paracelsus]], discovered the [[analgesic]] properties of diethyl ether around 1525.<ref name="Gravenstein1965"/> It was first synthesized in 1540 by [[Valerius Cordus]], who noted some of its medicinal properties.{{citation needed|date=September 2010}} He called it ''oleum dulce vitrioli'', a name that reflects the fact that it is synthesized by distilling a mixture of ethanol and [[sulfuric acid]] (known at that time as oil of vitriol). [[August Sigmund Frobenius]] gave the name ''Spiritus Vini Æthereus'' to the substance in 1730.<ref name="Frobenius1730"/><ref name="Mortimer1741"/>

==18th century==
[[File:Royal Institution - Humphry Davy.jpg|thumb|left|Satirical cartoon by [[James Gillray]] showing a [[Royal Institution]] lecture, with [[Humphry Davy]] holding the bellows and [[Benjamin Thompson|Count Rumford]] looking on at extreme right]]

[[Joseph Priestley]] (1733–1804) was an English [[polymath]] who discovered [[nitrous oxide]], [[nitric oxide]], [[ammonia]], [[hydrogen chloride]], and (along with [[Carl Wilhelm Scheele]] and [[Antoine Lavoisier]]) [[oxygen]]. Beginning in 1775, Priestley published his research in ''[[Experiments and Observations on Different Kinds of Air]]'', a six-volume work.<ref name="Priestley1775"/> The recent discoveries about these and other [[gas]]es stimulated a great deal of interest in the European scientific community. [[Thomas Beddoes]] (1760–1808) was an English [[philosophy|philosopher]], physician and teacher of medicine, and like his older colleague Priestley, was also a member of the [[Lunar Society of Birmingham]]. 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]].<ref name="Levere1977"/> 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. Other members of the Lunar Society such as [[Erasmus Darwin]] and [[Josiah Wedgwood]] were also actively involved with the institute.

During the course of his research at the Pneumatic Institution, Davy discovered the anesthetic properties of nitrous oxide.<ref name="Sneader2005"/> Davy, who coined the term "laughing gas" for nitrous oxide, published his findings the following year in the now-classic [[treatise]], ''Researches, chemical and philosophical–chiefly concerning nitrous oxide or dephlogisticated nitrous air, and its respiration''. 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:<ref name="Davy1800"/>

{{blockquote|As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place.}}

==19th century==
===Eastern hemisphere===
[[File:HanaokaSeishu.gif|thumb|upright|[[Hanaoka Seishū]], a Japanese surgeon of the 18th and 19th centuries]]

[[Takamine Tokumei]] from [[Shuri, Okinawa|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 Domain|Satsuma]] doctors in 1690 and to Ryūkyūan doctors in 1714.<ref>Arashiro Toshiaki, ''Ryukyu-Okinawa Rekishi Jinbutusuden OkinawaJijishuppan'', 12006. pp. 66–68</ref>

[[Hanaoka Seishū]] (華岡 青洲, 1760–1835) of [[Osaka]] was a Japanese surgeon of the [[Edo period]] with a knowledge of [[Chinese herbology|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.<ref name="Izuo2004"/> 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:<ref name="Ogata1973"/><ref name="Hyodo1992"/><ref name="BLTC"/>

* 2 parts ''bai zhi'' (''[[Chinese character|Chinese]]:白芷''，''Angelica dahurica'');
* 2 parts ''cao wu'' (''[[Chinese character|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|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 [[hyoscine hydrobromide|scopolamine]], [[hyoscyamine]], [[atropine]], [[aconitine]] and [[angelicotoxin]]. When consumed in sufficient quantity, tsūsensan produces a state of general anesthesia and [[skeletal muscle]] [[paralysis]].<ref name="BLTC"/> [[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.<ref name="Matsuki1999"/>

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.<ref name="Izuo2004"/><ref name="Hyodo1992"/><ref name="Perrin1979"/><ref name="Matsuki2000"/> Hanaoka went on to perform many operations using tsūsensan, including resection of [[malignancy|malignant]] [[tumor]]s, extraction of [[bladder stone]]s, and extremity [[amputation]]s. Before his death in 1835, Hanaoka performed more than 150 operations for breast cancer.<ref name="Izuo2004"/><ref name="Matsuki2000"/><ref name="Tominaga1994"/><ref name="Matsuki2002"/>

===Western hemisphere===
[[File:Colton Gardner Q.jpg|thumb|upright|[[Gardner Quincy Colton]], 19th-century American dentist]]
[[File:Wells Horace.jpg|thumb|upright|[[Horace Wells]], 19th-century American dentist]]
[[File:CrawfordLong.jpg|thumb|upright|[[Crawford Long|Crawford W. Long]], 19th-century American physician]]
[[File:WilliamMorton.jpg|thumb|upright|[[William T. G. Morton]], 19th-century American dentist]]

[[Friedrich Sertürner]] (1783–1841) first isolated [[morphine]] from [[opium]] in 1804;<ref name="Meyer2004"/> he named it morphine after [[Morpheus]], the Greek god of dreams.<ref name="Serturner1806"/>{{full citation needed|date=November 2016}}<ref name="Serturner1817"/>{{full citation needed|date=November 2016}}

[[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.<ref name="Desai2007"/> Four notable men participated in these events and witnessed the use of ether in this manner. They were [[William Edward Clarke]] (1819–1898), [[Crawford Long|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.<ref name="Sims1877"/><ref name="Lyman1881"/><ref name="Lyman1886"/><ref name="Richmond1950"/> In January 1842, by now a medical student at [[University of Vermont College of Medicine|Berkshire Medical College]], Clarke administered ether to a Miss Hobbie, while [[Elijah Pope]] performed a [[dental extraction]].<ref name="Lyman1881"/> 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.<ref name="Stone1898"/>

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.<ref name="Long1849"/> 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.<ref name="Long1849"/>

With the beginnings of modern medicine the stage was set for physicians and surgeons to build a paradigm in which anesthesia became useful.<ref name="Snow2005"/>

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.<ref name="Wells1847"/>

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]].<ref name="Morton1847"/> 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.<ref name="Fenster2001"/> [[Robert Liston]] performed the first amputation in December of that year. Morton published his experience soon after.<ref name="Morton1847"/> [[Harvard University]] professor [[Charles Thomas Jackson]] (1805–1880) later claimed that Morton stole his idea;<ref name="Jackson1861"/> Morton disagreed and a lifelong dispute began.<ref name="Fenster2001"/> 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.<ref name="Northen1910"/>

In 1847, Scottish [[obstetrics|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 [[liver|hepatic]] and [[heart|cardiac]] [[toxicity]], especially its tendency to cause potentially fatal [[cardiac dysrhythmia]]s, 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.<ref name="Snow2005"/> [[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.<ref name="Caton2000"/> 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.<ref name="Brodsky2007"/> 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.<ref name="Snow2005"/>

After Austrian diplomat [[Karl von Scherzer]] brought back sufficient quantities of coca leaves from Peru, in 1860 [[Albert Niemann (chemist)|Albert Niemann]] isolated cocaine, which thus became the first local anesthetic.<ref name="Wawersik1991"/><ref name="Bain1964"/>

In 1871, the German surgeon [[Friedrich Trendelenburg]] (1844–1924) published a paper describing the first successful [[elective surgery|elective]] human [[tracheotomy]] to be performed for the purpose of administration of general anesthesia.<ref name="Trendelenburg1871"/><ref name="Hargrave1934"/><ref name="Reutsch2001"/><ref name="Niemann1860"/>

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]].<ref name="Macewen18800724"/><ref name="Macewen18800731"/><ref name="Macmillan2010"/> All previous observations of the glottis and larynx (including those of [[Manuel Patricio Rodríguez García|Manuel García]],<ref name="Garcia1855"/> [[Wilhelm Hack]]<ref name="Hack1878-sammlung"/><ref name="Hack1878-uber"/> 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''.<ref name="Hirsch1986"/> The death of [[Frederick III, German Emperor|Emperor Frederick III]] (1831–1888)<ref name="Mackenzie1888"/> may have motivated Kirstein to develop the autoscope.<ref name="Burkle2004"/>

==20th century==
[[File:Hermann Emil Fischer c1895.jpg|thumb|upright|[[Hermann Emil Fischer]], German [[chemist]]]]

The 20th century saw the transformation of the practices of tracheotomy, [[endoscopy]] and non-surgical tracheal intubation from rarely employed procedures to essential components of the practices of anesthesia, [[intensive-care medicine|critical care medicine]], [[emergency medicine]], [[gastroenterology]], pulmonology, and surgery.

In 1902, [[Hermann Emil Fischer]] (1852–1919) and [[Joseph von Mering]] (1849–1908) discovered that [[barbital|diethylbarbituric acid]] was an effective [[hypnotic]] agent.<ref name="Fischer1903"/> Also called barbital or ''Veronal'' (the [[trade name]] assigned to it by [[Bayer|Bayer Pharmaceuticals]]), this new drug became the first commercially marketed [[barbiturate]]; it was used as a treatment for [[insomnia]] from 1903 until the mid-1950s.

Until 1913, [[oral and maxillofacial surgery]] was performed by mask [[inhalational anaesthetic|inhalation anesthesia]], topical application of [[local anesthetic]]s to the [[mucous membrane|mucosa]], rectal anesthesia, or [[intravenous therapy|intravenous]] anesthesia. While otherwise effective, these techniques did not protect the airway from obstruction and also exposed patients to the risk of pulmonary aspiration of blood and [[mucus]] into the tracheobronchial tree. In 1913, [[Chevalier Jackson]] (1865–1958) was the first to report a high rate of success for the use of direct laryngoscopy as a means to intubate the trachea.<ref name="Jackson1913"/> Jackson introduced a new laryngoscope blade that had a light source at the distal tip, rather than the proximal light source used by Kirstein.<ref name="Zeitels1998"/> This new blade incorporated a component that the operator could slide out to allow room for passage of an endotracheal tube or bronchoscope.<ref name="Jackson1922"/>

Also in 1913, [[Henry H. Janeway]] (1873–1921) published results he had achieved using a laryngoscope he had recently developed.<ref name="Janeway1913"/> An American anesthesiologist practicing at [[Bellevue Hospital Center|Bellevue Hospital]] in [[New York City]], Janeway was of the opinion that direct intratracheal [[insufflation (medicine)|insufflation]] of [[inhalational anesthetic|volatile anesthetics]] would provide improved conditions for [[otolaryngology|otolaryngologic]] surgery. With this in mind, he developed a laryngoscope designed for the sole purpose of tracheal intubation. Similar to Jackson's device, Janeway's instrument incorporated a distal light source. Unique, however, was the inclusion of [[battery (electricity)|batteries]] within the handle, a central notch in the blade for maintaining the tracheal tube in the midline of the oropharynx during intubation and a slight curve to the distal tip of the blade to help guide the tube through the glottis. The success of this design led to its subsequent use in other types of surgery. Janeway was thus instrumental in popularizing the widespread use of direct laryngoscopy and tracheal intubation in the practice of anesthesiology.<ref name="Burkle2004"/>

In 1928 [[Arthur Ernest Guedel]] introduced the cuffed endotracheal tube, which allowed deep enough anesthesia that completely suppressed spontaneously respirations while the gas and oxygen were delivered via positive pressure ventilation controlled by the anesthesiologist.<ref name="Guedel928"/> Also important for the development of modern anesthesia are [[anaesthetic machine|anesthesia machines]]. Only three years later Joseph W. Gale developed the technology where the anesthesiologist was able to ventilate only one lung at a time.<ref name="Gale1932"/> This allowed the development of thoracic surgery, which had previously been vexed by the pendelluft <ref name="Greenblatt2014"/> problem in which the bad lung being operated on inflated with patient exhalation due to the loss of vacuum with the thorax being open to the atmosphere. Eventually by early 1980s double lumen endotracheal tubes made out of clear plastic enabled anesthesiologists to selectively ventilate one lung while using flexible fiberoptic bronchoscopy to block off the diseased lung and prevent cross contamination.<ref name="Brodsky2007"/> One early device, the copper kettle, was developed by Dr. Lucien E. Morris at the University of Wisconsin.<ref name="Morris1952"/><ref name="Morris2006"/>

[[Sodium thiopental]], the first [[intravenous anesthetic]], was synthesized in 1934 by [[Ernest H. Volwiler]] (1893–1992) and [[Donalee L. Tabern]] (1900–1974), working for [[Abbott Laboratories]].<ref name="Tabern1935"/> It was first used in humans on 8 March 1934 by [[Ralph M. Waters]] in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia. Three months later, [[John Silas Lundy]] started a clinical trial of thiopental at the [[Mayo Clinic]] at the request of Abbott Laboratories. Volwiler and Tabern were awarded U.S. Patent No. 2,153,729 in 1939 for the discovery of thiopental, and they were inducted into the National Inventors Hall of Fame in 1986.

In 1939, the search for a synthetic substitute for atropine culminated serendipitously in the discovery of meperidine, the first opiate with a structure altogether different from that of morphine.<ref name="Eisleb1939"/> This was followed in 1947 by the widespread introduction of methadone, another structurally unrelated compound with pharmacological properties similar to those of morphine.<ref name="Scott1946"/>

After [[World War I]], further advances were made in the field of intratracheal anesthesia. Among these were those made by Sir [[Ivan Magill|Ivan Whiteside Magill]] (1888–1986). Working at the [[Frognal House|Queen's Hospital for Facial and Jaw Injuries]] in [[Sidcup]] with plastic surgeon Sir [[Harold Gillies]] (1882–1960) and anesthetist [[E. Stanley Rowbotham]] (1890–1979), Magill developed the technique of awake blind nasotracheal intubation.<ref name="Rowbotham1921"/><ref name="Magill1923-provision"/><ref name="Magill1928"/><ref name="Magill1930"/><ref name="Thomas1978"/><ref name="Mclachlan2008"/> Magill devised a new type of angulated forceps (the [[Magill forceps]]) that are still used today to facilitate nasotracheal intubation in a manner that is little changed from Magill's original technique.<ref name="Magill1920"/> Other devices invented by Magill include the Magill laryngoscope blade,<ref name="Magill1926"/> as well as several apparatuses for the administration of volatile anesthetic agents.<ref name="Magill1921-portable"/><ref name="Magill1921-warming"/><ref name="Magill1923-apparatus"/> The Magill curve of an endotracheal tube is also named for Magill.

The first hospital anesthesia department was established at the Massachusetts General Hospital in 1936, under the leadership of [[Henry K. Beecher]] (1904–1976). Beecher, who received his training in surgery, had no previous experience in anesthesia.<ref>{{cite journal |last1=Gravenstein |first1=Joachim |title=Henry K. Beecher: The Introduction of Anesthesia into the University |journal=Anesthesiology |volume=88 |issue=1 |date=January 1998 |pages=245–253 |pmid=9447878 |s2cid=5944101 |doi=10.1097/00000542-199801000-00033 |url=https://pubs.asahq.org/anesthesiology/article/88/1/245/36479/Henry-K-Beecher-The-Introduction-of-Anesthesia|doi-access=free }}</ref>

Although initially used to reduce the sequelae of spasticity associated with [[electroconvulsive therapy]] for psychiatric disease, [[curare]] found use in the operating rooms at Bellvue by E.M. Papper and Stuart Cullen in the 1940s using preparations made by Squibb.<ref name="Betcher1977"/> This neuromuscular blockade permitted complete paralysis of the diaphragm and enabled control of ventilation via positive pressure ventilation.<ref name="Brodsky2007"/> [[Medical ventilator|Mechanical ventilation]] first became common place with the polio epidemics of the 1950s, most notably in Denmark where an outbreak in 1952 lead to the creation of critical care medicine out of anesthesia. At first anesthesiologists hesitated to bring the ventilator into the operating theater unless necessary, but by the 1960s it became standard operating room equipment.<ref name="Brodsky2007"/>

Sir [[Robert Macintosh]] (1897–1989) achieved significant advances in techniques for tracheal intubation when he introduced his new curved laryngoscope blade in 1943.<ref name="Macintosh1943"/> The Macintosh blade remains to this day the most widely used laryngoscope blade for orotracheal intubation.<ref name="Scott2009"/> In 1949, Macintosh published a case report describing the novel use of a [[natural rubber|gum elastic]] [[urinary catheterization#Catheter types|urinary catheter]] as an endotracheal tube introducer to facilitate difficult tracheal intubation.<ref name="Macintosh1949"/> Inspired by Macintosh's report, P. Hex Venn (who was at that time the anesthetic advisor to the British firm Eschmann Bros. & Walsh, Ltd.) set about developing an endotracheal tube introducer based on this concept. Venn's design was accepted in March 1973, and what became known as the Eschmann endotracheal tube introducer went into production later that year.<ref name="Venn1993"/> The material of Venn's design was different from that of a gum elastic bougie in that it had two layers: a core of tube woven from [[polyester]] threads and an outer [[resin]] layer. This provided more stiffness but maintained the flexibility and the slippery surface. Other differences were the length (the new introducer was {{convert|60|cm|0|abbr=on}}, which is much longer than the gum elastic bougie) and the presence of a 35° curved tip, permitting it to be steered around obstacles.<ref name="Viswanathan1992"/><ref name="Henderson2003"/>

For over a hundred years the mainstay of inhalational anesthetics remained [[diethyl ether|ether]] with [[cyclopropane]], which had been introduced in the 1930s. In 1956 [[halothane]]<ref name="Raventos1956"/> was introduced which had the significant advantage of not being flammable. This reduced the risk of operating room fires. In the sixties the [[halogenated ether]]s superseded [[Halothane]] due to the rare, but significant side effects of cardiac arrhythmias and liver toxicity. The first two halogenated ethers were [[methoxyflurane]] and [[enflurane]]. These in turn were replaced by the current standards of [[isoflurane]], [[sevoflurane]], and [[desflurane]] in the eighties and nineties although [[methoxyflurane]] remains in use for prehospital anesthesia in Australia as Penthrox. [[Halothane]] remains in common place throughout much of the developing world.

Many new intravenous and inhalational anesthetics were developed and brought into clinical use during the second half of the 20th century. [[Paul Janssen]] (1926–2003), the founder of [[Janssen Pharmaceutica]], is credited with the development of over 80 pharmaceutical compounds.<ref name="Stanley2008"/> Janssen synthesized nearly all of the [[butyrophenone]] class of [[antipsychotic]] agents, beginning with [[haloperidol]] (1958) and [[droperidol]] (1961).<ref name="Janssen1963d"/> These agents were rapidly integrated into the practice of anesthesia.<ref name="Castro1959"/><ref name="Nilsson1961"/><ref name="Aubry1966"/><ref name="Corrsen1966"/><ref name="Reyes1969"/> In 1960, Janssen's team synthesized [[fentanyl]], the first of the [[N-Phenethyl-4-piperidinone|piperidinone]]-derived opioids.<ref name="Janssen1960f"/><ref name="Janssen1963f"/> Fentanyl was followed by [[sufentanil]] (1974),<ref name="Niemegeers1976"/> [[alfentanil]] (1976),<ref name="Spierdijk1980"/><ref name="Niemegeers1981"/> [[carfentanil]] (1976),<ref name="DeVos1978"/> and [[lofentanil]] (1980).<ref name="Laduron1982"/> Janssen and his team also developed [[etomidate]] (1964),<ref name="Doenicke1973"/><ref name="Morgan1975"/> a potent intravenous anesthetic induction agent.

The concept of using a fiberoptic endoscope for tracheal intubation was introduced by [[Peter Murphy (anaesthetist)|Peter Murphy]], an English anesthetist, in 1967.<ref name="Murphy1967"/> By the mid-1980s, the flexible fiberoptic bronchoscope had become an indispensable instrument within the [[pulmonology]] and anesthesia communities.<ref name="Wheeler2007"/>

==21st century==
[[File:Maquet Flow-I anesthesia machine.jpg|thumb|upright|A modern anaesthetic machine. This particular machine is a "Flow-I" model, manufactured by [[Maquet]].]]

The [[Information Age|"digital revolution"]] of the 21st century has brought newer technology to the art and science of tracheal intubation. Several manufacturers have developed [[laryngoscopy#Video laryngoscope|video laryngoscopes]] which employ [[digital electronics|digital technology]] such as the [[CMOS]] [[active pixel sensor]] (APS) to generate a view of the glottis so that the trachea may be intubated. The Glidescope video laryngoscope is one example of such a device.<ref name="Agro2003"/><ref name="Cooper2005"/>

[[Xenon]], which does not act as a greenhouse gas, has recently been approved in some jurisdictions as an anaesthetic agent.<ref name="Tonner2006"/>
{{Clear}}

==See also==
{{Portal|History|Medicine}}
{{Columns-list|colwidth=30em|
* [[ACE mixture]]
* [[American Association of Nurse Anesthesiology]]
* [[American Society of Anesthesiologists]]
* [[Anaesthetic machine]]
* [[ASA physical status classification system]]
* [[Blood transfusion]]
* [[Henry Edmund Gaskin Boyle]]
* [[Walter Channing (physician)]]
* [[Joseph Thomas Clover]]
* [[Curare]]
* [[James Esdaile]]
* [[General anaesthesia]]
* [[Arthur Ernest Guedel]]
* [[History of anatomy]]
* [[History of medicine]]
* [[History of neuraxial anesthesia]]
* [[History of neuroscience]]
* [[History of surgery]]
* [[History of tracheal intubation]]
* [[Local anesthesia]]
* [[Fidel Pagés]]
* [[Royal College of Anaesthetists]]
* [[John Snow]]
* [[Takamine Tokumei]]
* [[The Zoist|The Zoist: A Journal of Cerebral Physiology & Mesmerism, and Their Applications to Human Welfare]]
}}

==References==
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<ref name="Doenicke1973">{{cite journal |vauthors=Doenicke A, Kugler J, Penzel G, Laub M, Kalmar L, Kilian I, Bezecny H |title=[Cerebral function under etomidate, a new non-barbiturate i.v. hypnotic] |journal=Der Anaesthesist |volume=22 |issue=8 |date=August 1973 |pages=353–66 |language=de |issn=0003-2417 |pmid=4584133 |url=http://tematicas.es/salud/articulo/hirnfunktion-und-toleranzbreite-nach-etomidate-einem-neuen-barbituratfreien-i-v-applizierbaren-hypnoticum/ |access-date=2010-09-27 |url-status=dead |archive-url=https://web.archive.org/web/20110720143625/http://tematicas.es/salud/articulo/hirnfunktion-und-toleranzbreite-nach-etomidate-einem-neuen-barbituratfreien-i-v-applizierbaren-hypnoticum/ |archive-date=20 July 2011}}</ref>

<ref name="Dwarakanath1965">{{cite journal |author=Dwarakanath SC |title=Use of opium and cannabis in the traditional systems of medicine in India |journal=Bulletin on Narcotics |volume=17 |issue=1 |pages=15–9 |year=1965 |issn=0007-523X |url=http://unosek.org/unodc/en/data-and-analysis/bulletin/bulletin_1965-01-01_1_page004.html |access-date=2010-09-27 |url-status=dead |archive-url=https://web.archive.org/web/20110728145435/http://unosek.org/unodc/en/data-and-analysis/bulletin/bulletin_1965-01-01_1_page004.html |archive-date=2011-07-28}}</ref>

<ref name="Ebbell1937">{{cite book |title=The Papyrus Ebers: The greatest Egyptian medical document |author=Ebbell B |publisher=Levin & Munksgaard |location=Copenhagen |year=1937 |df=dmy-all |url=http://www.macalester.edu/~cuffel/ebers.htm |access-date=2010-09-18 |url-status=dead |archive-url=https://web.archive.org/web/20050226100008/http://www.macalester.edu/~cuffel/ebers.htm |archive-date=26 February 2005}}</ref>

<ref name="Ebers1889">{{cite book |title=Papyrus Ebers |edition=1 |volume=2 |author=Ludwig Christian Stern |editor=Ebers G |editor-link=Georg Ebers |publisher=Bei S. Hirzel |location=Leipzig |language=de |year=1889 |oclc=14785083 |url=https://archive.org/details/papyrusebersdie00ebergoog |access-date=2010-09-18}}</ref>

<ref name="Eisleb1939">Eisleb, 0. & Schaumann, 0. (1939) ''Deutsche Medizinische Wochenschrift'' '''65''', 967–968.</ref>

<ref name="Fenster2001">{{cite book |last=Fenster |first=JM |title=Ether Day: The Strange Tale of America's Greatest Medical Discovery and the Haunted Men Who Made It |place=New York |publisher=[[HarperCollins]] |year=2001 |isbn=978-0-06-019523-6 |url=https://archive.org/details/etherdaystranget00fens}}</ref>

<ref name="Fischer1903">{{cite journal |author1=Fischer EH |author2=Mering J |author-link1=Hermann Emil Fischer |title=Ueber eine neue Klasse von Schlafmitteln |journal=Die Therapie der Gegenwart |volume=5 |date=March 1903 |pages=97–101 |language=de |url=https://books.google.com/books?id=NV0DAAAAYAAJ&q=%22Therapie+der+Gegenwart%22+1903 |access-date=2010-09-13}}</ref>

<ref name="Fort1965">{{cite journal |author=Fort J |title=Giver of delight or Liberator of sin: Drug use and "addiction" in Asia |journal=Bulletin on Narcotics |volume=17 |issue=3 |pages=1–11 |year=1965 |issn=0007-523X |url=http://unosek.org/unodc/en/data-and-analysis/bulletin/bulletin_1965-01-01_3_page002.html |access-date=2010-09-27 |url-status=dead |archive-url=https://web.archive.org/web/20110728145444/http://unosek.org/unodc/en/data-and-analysis/bulletin/bulletin_1965-01-01_3_page002.html |archive-date=2011-07-28}}</ref>

<ref name="Frobenius1730">{{cite journal |last=Frobenius |first=AS |author-link=August Sigmund Frobenius |title=An Account of a Spiritus Vini Æthereus, Together with Several Experiments Tried Therewith |journal=Philosophical Transactions |volume=36 |issue=413 |date=1 January 1729 |pages=283–9 |s2cid=186207852 |doi=10.1098/rstl.1729.0045}}</ref>

<ref name="Fu2002">{{cite journal |author=Fu LK |title=Hua Tuo, the Chinese god of surgery |journal=Journal of Medical Biography |volume=10 |issue=3 |date=August 2002 |pages=160–6 |pmid=12114950 |s2cid=31655903 |doi=10.1177/096777200201000310 |url=http://grande.nal.usda.gov/ibids/index.php?mode2=detail&therow=708782 |access-date=2010-09-13 |url-status=dead |archive-url=https://web.archive.org/web/20090719234737/http://grande.nal.usda.gov/ibids/index.php?mode2=detail |archive-date=19 July 2009}}</ref>

<ref name="Garcia1855">{{cite journal |last=García |first=M |author-link=Manuel Patricio Rodríguez García |title=Observations on the Human Voice |journal=Proceedings of the Royal Society of London |volume=7 |date=24 May 1855 <!-- date on page 380--> |pages=399–410 |issue=60 |pmid=30163547 |bibcode=1854RSPS....7..399G |pmc=5180321 |doi=10.1098/rspl.1854.0094 |url=https://books.google.com/books?id=o6PYNM7RNwkC&pg=PA399 |access-date=2010-09-13}}</ref>

<ref name="Giles1897">{{cite book |title=A Chinese Biographical Dictionary |pages=323–4, 762–3 |author=Giles HA |author-link=Herbert Giles |publisher=Bernard Quaritch |location=London |year=1898 |isbn=9780896440104 |url=https://books.google.com/books?id=BxH0PqdGTVUC&q=%22A+Chinese+Biographical+Dictionary%22 |access-date=2010-09-14 |quote=If a disease seemed beyond the reach of needles and cautery, he operated, giving his patients a dose of hashish which rendered them unconscious.}}</ref>

<ref name="Giles1912">{{cite book |title=Taoist teachings from the book of Lieh-Tzŭ, translated from the Chinese, with introduction and notes, by Lionel Giles (Wisdom of the East series) |author=Giles L (transl.) |author-link=Lionel Giles |publisher=John Murray |location=London |year=1912 |url=http://www.sacred-texts.com/tao/tt/index.htm |access-date=2010-09-14}}</ref>

<ref name="Giles1948">{{cite book |title=A Gallery of Chinese immortals: selected biographies, translated from Chinese sources by Lionel Giles (Wisdom of the East series) |edition=1 |author=Giles L (transl.) |author-link=Lionel Giles |editor=Cranmer-Byng JL |publisher=John Murray |location=London |year=1948 |url=http://www.angelfire.com/in4/alchemy2084/giles.html |access-date=2010-09-14 |quote=The well-attested fact that Hua T'o made use of an anaesthetic for surgical operations over 1,600 years before Sir James Simpson certainly places him to our eyes on a pinnacle of fame....}}</ref>

<ref name="Gordon1949">{{cite book |title=Medicine throughout Antiquity |edition=1 |pages=358, 379, 385, 387 |author=Gordon BL |publisher=F.A. Davis Company |location=Philadelphia |year=1949 |isbn=9780598609977 |oclc=1574261 |url=https://books.google.com/books?id=BDprAAAAMAAJ&q=%22Medicine+throughout+Antiquity%22 |access-date=2010-09-14 |quote=Pien Chiao (ca. 300 BC) used general anesthesia for surgical procedures. It is recorded that he gave two men, named "Lu" and "Chao", a toxic drink which rendered them unconscious for three days, during which time he performed a gastrotomy upon them}}</ref>

<ref name="Gravenstein1965">{{cite journal |author=Gravenstein JS |title=Paracelsus and his contributions to anesthesia |journal=Anesthesiology |volume=26 |issue=6 |date=November–December 1965 |pages=805–11 |pmid=5320896 |doi=10.1097/00000542-196511000-00016 |doi-access=free}}</ref>

<ref name="Hack1878-sammlung">{{cite journal |first=W |last=Hack |title=Über die mechanische Behandlung der Larynxstenosen |trans-title=On the mechanical treatment of laryngeal stenosis |volume=152 |language=de |journal=Sammlung Klinischer Vorträge |year=1878 |pages=52–75}}</ref>

<ref name="Hack1878-uber">{{cite journal |first=W |last=Hack |title=Über einen fall endolaryngealer exstirpation eines polypen der vorderen commissur während der inspirationspause |journal=Berliner Klinische Wochenschrift |language=de |pages=135–7 |date=March 1878 |url=https://books.google.com/books?id=VkzlAAAAMAAJ&pg=PA135 |access-date=2010-09-13}}</ref>

<ref name="Hargrave1934">{{cite journal |first=R |last=Hargrave |title=Endotracheal Anæsthesia in Surgery of the Head and Neck |journal=[[Canadian Medical Association Journal]] |volume=30 |issue=6 |date=June 1934 |pages=633–7 |pmc=403396 |pmid=20319535}}</ref>

<ref name="Henderson2003">{{cite journal |last=Henderson |first=JJ |title=Development of the 'gum-elastic bougie' |journal=Anaesthesia |volume=58 |issue=1 |date=January 2003 |pages=103–4 |pmid=12492697 |s2cid=34113322 |doi=10.1046/j.1365-2044.2003.296828.x |doi-access=free}}</ref>

<ref name="Hirsch1986">{{cite journal |last1=Hirsch |first1=NP |last2=Smith |first2=GB |last3=Hirsch |first3=PO |title=Alfred Kirstein. Pioneer of direct laryngoscopy |journal=Anaesthesia |volume=41 |issue=1 |date=January 1986 |pages=42–5 |pmid=3511764 |s2cid=12259652 |doi=10.1111/j.1365-2044.1986.tb12702.x |doi-access=free}}</ref>

<ref name="Hunke1969">{{cite book |title=Allahs Sonne über dem Abendland: unser arabisches Erbe |edition=2 |pages=279–80 |author=Hunke S |author-link=Sigrid Hunke |publisher=Deutsche Verlags-Anstalt |location=Stuttgart |language=de |year=1960 |isbn=978-3-596-23543-8 |url=https://books.google.com/books?id=wlIuAAAAIAAJ&q=%22Allahs+Sonne+%C3%BCber+dem+Abendland:+unser+arabisches+Erbe%22 |access-date=2010-09-13 |quote=The science of medicine has gained a great and extremely important discovery and that is the use of general anaesthetics for surgical operations, and how unique, efficient, and merciful for those who tried it the Muslim anaesthetic was. It was quite different from the drinks the Indians, Romans and Greeks were forcing their patients to have for relief of pain. There had been some allegations to credit this discovery to an Italian or to an Alexandrian, but the truth is and history proves that, the art of using the anaesthetic sponge is a pure Muslim technique, which was not known before. The sponge used to be dipped and left in a mixture prepared from cannabis, opium, hyoscyamus, and a plant called Zoan.}}</ref>

<ref name="Hyodo1992">{{cite book |title=The Pain Clinic IV: proceedings of the fourth international symposium |chapter=Doctor S. Hanaoka, the world's-first success in providing general anesthesia |pages=3–12 |author=Hyodo M |veditors=Hyodo M, Oyama T, Swerdlow M |publisher=VSP |location=Utrecht, Netherlands |year=1992 |isbn=978-90-6764-147-0 |chapter-url=https://books.google.com/books?id=ljBTn8HBBjcC&q=%22Doctor%20S.%20Hanaoka%2C%20the%20World's-First%20Success%20in%20Providing%20General%20Anesthesia%22&pg=PA3 |access-date=2010-09-13}}</ref>

<ref name="Izuo2004">{{cite journal |last=Izuo |first=M |title=Medical history: Seishū Hanaoka and his success in breast cancer surgery under general anesthesia two hundred years ago |journal=Breast Cancer |volume=11 |issue=4 |date=November 2004 |pages=319–24 |pmid=15604985 |s2cid=43428862 |doi=10.1007/BF02968037}}</ref>

<ref name="Jackson1861">{{cite book |author=Jackson CT |author-link=Charles Thomas Jackson |title=A Manual of Etherization: Containing Directions for the Employment of Ether |year=1861 |publisher=J.B. Mansfield |location=Boston |url=https://books.google.com/books?id=LiEJAAAAIAAJ |access-date=2010-09-13}}</ref>

<ref name="Jackson1913">{{cite journal |last=Jackson |first=C |title=The technique of insertion of intratracheal insufflation tubes |journal=Surgery, Gynecology & Obstetrics |volume=17 |pages=507–9 |year=1913}} Reprinted in {{cite journal |last1=Jackson |first1=Chevalier |title=The technique of insertion of intratracheal insufflation tubes |journal=Pediatric Anesthesia |volume=6 |date=May 1996 |page=230 |issue=3 |s2cid=72582327 |doi=10.1111/j.1460-9592.1996.tb00434.x}}</ref>

<ref name="Jackson1922">{{cite book |last=Jackson |first=C |title=A manual of peroral endoscopy and laryngeal surgery |chapter=I: Instrumentarium |publisher=W.B. Saunders |location=Philadelphia |year=1922 |pages=17–52 |chapter-url=http://mybebook.com/download_free_ebook/jackson-chevalier-1865-1958_ebooks/bronchoscopy-and-esophagoscopya-manual-of-peroral-endoscopy-and-laryngeal-surgery/ebook13336.pdf |isbn=978-1-4326-6305-6 |access-date=2010-09-13}}</ref>

<ref name="Janeway1913">{{cite journal |last=Janeway |first=HH |title=Intra-tracheal anesthesia from the standpoint of the nose, throat and oral surgeon with a description of a new instrument for catheterizing the trachea |journal=The Laryngoscope |volume=23 |issue=11 |date=November 1913 |pages=1082–90 |s2cid=71549386 |doi=10.1288/00005537-191311000-00009 |url=https://zenodo.org/record/1448738}}</ref>

<ref name="Janssen1960f">{{cite journal |last1=J. |first1=PA |last2=Eddy |first2=NB |title=Compounds Related to Pethidine--IV. New General Chemical Methods of Increasing the Analgesic Activity of Pethidine |journal=Journal of Medicinal Chemistry |volume=2 |date=February 1960 |pages=31–45 |pmid=14406754 |issue=1 |doi=10.1021/jm50008a003}}</ref>

<ref name="Janssen1963d">{{cite journal |last1=Janssen |first1=PA |last2=Niemegeers |first2=CJ |last3=Schellekens |first3=KH |last4=Verbruggen |first4=FJ |last5=Van Nueten |first5=JM |title=The pharmacology of dehydrobenzperidol, a new potent and short acting neuroleptic agent chemically related to Haloperidol |journal=Arzneimittel-Forschung |volume=13 |date=March 1963 |pages=205–11 |pmid=13957425}}</ref>

<ref name="Janssen1963f">{{cite journal |pmid=13957426 |last1=Janssen |year=1963 |first1=PA |pages=502–7 |last2=Niemegeers |volume=13 |journal=Arzneimittel-Forschung |first2=CJ |last3=Dony |first3=JG |title=The inhibitory effect of fentanyl and other morphine-like analgesics on the warm water induced tail withdrawal reflex in rats |url=http://garfield.library.upenn.edu/classics1991/A1991GA09000001.pdf}}</ref>

<ref name="Kramer1954">{{cite journal |last1=Kramer |first1=SN |author-link=Samuel Noah Kramer |title=First pharmacopeia in man's recorded history |journal=American Journal of Pharmacy and the Sciences Supporting Public Health |volume=126 |issue=3 |date=March 1954 |pages=76–84 |issn=0002-9467 |pmid=13148318}}</ref>

<ref name="Kramer1988">{{cite book |title=History Begins at Sumer: Thirty-Nine Firsts in Recorded History |edition=3 |vauthors=Kramer SN, Tanaka H |author-link=Samuel Noah Kramer |publisher=University of Pennsylvania Press |location=Philadelphia |date=March 1988 |isbn=978-0-8122-1276-1 |url=https://archive.org/details/humansideofjapan00tana}}</ref>

<ref name="Krikorian1975">{{cite journal |last=Krikorian |first=AD |title=Were the opium poppy and opium known in the ancient Near East? |journal=Journal of the History of Biology |volume=8 |issue=1 |date=March 1975 |pages=95–114 |pmid=11609871 |s2cid=23899398 |doi=10.1007/BF00129597}}</ref>

<ref name="Kritikos1967-2">{{cite journal |title=The History of the Poppy and of Opium and Their Expansion in Antiquity in the Eastern Mediterranean Area |vauthors=Kritikos PG, Papadaki SP |journal=Bulletin on Narcotics |volume=19 |issue=4 |pages=5–10 |year=1967 |issn=0007-523X}}</ref>

<ref name="Kritikos1967-3">{{cite journal |title=The history of the poppy and of opium and their expansion in antiquity in the eastern Mediterranean area |vauthors=Kritikos PG, Papadaki SP |journal=Bulletin on Narcotics |volume=19 |issue=3 |pages=17–38 |year=1967 |issn=0007-523X |url=http://unosek.org/unodc/en/data-and-analysis/bulletin/bulletin_1967-01-01_3_page004.html |access-date=2010-09-18 |url-status=dead |archive-url=https://web.archive.org/web/20110728144432/http://unosek.org/unodc/en/data-and-analysis/bulletin/bulletin_1967-01-01_3_page004.html |archive-date=2011-07-28}}</ref>

<ref name="Laduron1982">{{cite journal |last1=Laduron |first1=P |last2=Janssen |first2=PF |title=Axoplasmic transport and possible recycling of opiate receptors labelled with 3H-lofentanil |journal=Life Sciences |volume=31 |issue=5 |date=August 1982 |pages=457–62 |pmid=6182434 |doi=10.1016/0024-3205(82)90331-9}}</ref>
<ref name="Levere1977">{{cite journal |last=Levere |first=TH |title=Dr. Thomas Beddoes and the establishment of his Pneumatic Institution: a tale of three presidents |journal=Notes and Records of the Royal Society |volume=32 |issue=1 |date=July 1977 |pages=41–9 |pmid=11615622 |jstor=531764 |s2cid=27322059 |doi=10.1098/rsnr.1977.0005}}</ref>

<ref name="Long1849">{{cite journal |author=Long CW |author-link=Crawford Long |title=An account of the first use of Sulphuric Ether by Inhalation as an Anaesthetic in Surgical Operations |journal=Southern Medical and Surgical Journal |volume=5 |pages=705–13 |date=December 1849 |url=http://journals.lww.com/surveyanesthesiology/Citation/1991/12000/An_Account_of_the_First_Use_of_Sulphuric_Ether_by.49.aspx}} reprinted in {{cite journal |last1=Long |first1=C. W. |title=An account of the first use of Sulphuric Ether by Inhalation as an Anaesthetic in Surgical Operations |journal=Survey of Anesthesiology |volume=35 |issue=6 |page=375 |date=December 1991 |doi=10.1097/00132586-199112000-00049}}</ref>

<ref name="Lu2002">{{cite book |title=Celestial lancets: a history and rationale of acupuncture and moxa |chapter=Acupuncture and major surgery |pages=218–30 |author1=Lu GD |author2=Needham J |publisher=RoutledgeCurzon |location=London |year=2002 |isbn=978-0-7007-1458-2 |chapter-url=https://books.google.com/books?id=0-0tdqBr58cC&q=Celestial+Lancets:+A+History+and+Rationale+of+Acupuncture+and+Moxa |access-date=2010-09-13}}</ref>

<ref name="Lyman1881">{{cite book |title=Artificial anaesthesia and anaesthetics |chapter=History of anaesthesia |page=6 |author=Lyman HM |year=1881 |publisher=William Wood and Company |location=New York |chapter-url=https://books.google.com/books?id=xNEIAQAAIAAJ&q=Artificial%20anaesthesia%20and%20anaesthetics&pg=PA68 |access-date=2010-09-13}}</ref>

<ref name="Lyman1886">{{cite journal |author=Lyman HM |title=The discovery of anesthesia |journal=Virginia Medical Monthly |volume=13 |issue=6 |pages=369–92 |date=September 1886 |url=https://books.google.com/books?id=bkYVAAAAYAAJ&q=%22The%20Discovery%20of%20Anaesthesia%22%20Virginia%20Medical%20Monthly&pg=PA369 |access-date=2010-09-13}}</ref>

<ref name="Macewen18800724">{{cite journal |first=W |last=Macewen |title=General Observations on the Introduction of Tracheal Tubes by the Mouth, Instead of Performing Tracheotomy or Laryngotomy |journal=British Medical Journal |volume=2 |issue=1021 |date=July 1880 |pages=122–4 |pmid=20749630 |pmc=2241154 |doi=10.1136/bmj.2.1021.122}}</ref>

<ref name="Macewen18800731">{{cite journal |first=W |last=Macewen |author-link=William Macewen |title=Clinical Observations on the Introduction of Tracheal Tubes by the Mouth, Instead of Performing Tracheotomy or Laryngotomy |journal=[[BMJ|British Medical Journal]] |volume=2 |issue=1022 |date=July 1880 |pages=163–5 |pmid=20749636 |pmc=2241109 |doi=10.1136/bmj.2.1022.163}}</ref>

<ref name="Macintosh1943">{{cite journal |first=RR |last=Macintosh |author-link=Robert Reynolds Macintosh |title=A new laryngoscope |journal=The Lancet |volume=241 |issue=6233 |date=13 February 1943 |page=205 |doi=10.1016/S0140-6736(00)89390-3}}</ref>

<ref name="Macintosh1949">{{cite journal |first=RR |last=Macintosh |title=Marxist Genetics |journal=British Medical Journal |volume=1 |issue=4591 |date=1 January 1949 |pages=26–28 |pmc=2049235 |doi=10.1136/bmj.1.4591.26-b}}</ref>

<ref name="Mackenzie1888">{{cite book |first=M |last=Mackenzie |author-link=Morell Mackenzie |title=The case of Emperor Frederick III.: full official reports by the German physicians and by Sir Morell Mackenzie |publisher=Edgar S. Werner |location=New York |year=1888 |page=276 |url=https://books.google.com/books?id=G2DTAAAAMAAJ&pg=PA276 |access-date=2010-09-13}}</ref>

<ref name="Macmillan2010">{{cite journal |last=Macmillan |first=M |title=William Macewen [1848–1924] |journal=Journal of Neurology |volume=257 |issue=5 |date=May 2010 |pages=858–9 |pmid=20306068 |doi=10.1007/s00415-010-5524-5 |doi-access=free}}</ref>

<ref name="Magill1920">{{cite journal |first=I |last=Magill |title=Appliances and Preparations |journal=British Medical Journal |volume=2 |date=October 1920 |page=670 |pmc=2338485 |pmid=20770050 |issue=3122 |doi=10.1136/bmj.2.571.670}}</ref>

<ref name="Magill1921-portable">{{cite journal |first=I |last=Magill |title=A Portable Apparatus for Tracheal Insufflation Anaesthesia |journal=The Lancet |volume=197 |issue=5096 |date=30 April 1921 |page=918 |doi=10.1016/S0140-6736(00)55592-5}}</ref>

<ref name="Magill1921-warming">{{cite journal |first=I |last=Magill |title=Warming Ether Vapour for Inhalation |journal=The Lancet |volume=197 |issue=5102 |date=11 June 1921 |page=1270 |doi=10.1016/S0140-6736(01)24908-3 |url=https://zenodo.org/record/2511612}}</ref>

<ref name="Magill1923-apparatus">{{cite journal |first=I |last=Magill |title=An apparatus for the administration of nitrous oxide, oxygen, and ether |journal=The Lancet |volume=202 |issue=5214 |date=4 August 1923 |page=228 |doi=10.1016/S0140-6736(01)22460-X}}</ref>

<ref name="Magill1923-provision">{{cite journal |first=I |last=Magill |author-link=Ivan Magill |title=The provision for expiration in endotracheal insufflations anaesthesia |journal=[[The Lancet]] |volume=202 |issue=5211 |date=14 July 1923 |pages=68–9 |doi=10.1016/S0140-6736(01)37756-5}}</ref>

<ref name="Magill1926">{{cite journal |first=I |last=Magill |title=An improved laryngoscope for anaesthetists |journal=The Lancet |volume=207 |issue=5349 |date=6 March 1926 |page=500 |doi=10.1016/S0140-6736(01)17109-6}}</ref>

<ref name="Magill1928">{{cite journal |first=I |last=Magill |title=Endotracheal Anæsthesia |journal=Proceedings of the Royal Society of Medicine |volume=22 |issue=2 |date=December 1928 |pages=85–8 |pmc=2101959 |pmid=19986772}}</ref>

<ref name="Magill1930">{{cite journal |first=I |last=Magill |title=Technique in Endotracheal Anaesthesia |journal=British Medical Journal |volume=2 |date=November 1930 |pages=817–9 |pmc=2451624 |pmid=20775829 |issue=1243 |doi=10.1136/bmj.2.1243.817-a}}</ref>

<ref name="Mair2000">{{cite book |title=The shorter Columbia anthology of traditional Chinese literature |volume=Part III: Prose |chapter=The Biography of Hua-t'o from the History of the Three Kingdoms |pages=441–9 |author=Ch'en S |editor=Mair VH |publisher=Columbia University Press |location=New York |year=2000 |isbn=978-0-231-11998-6 |editor-link=Victor H. Mair |chapter-url=https://books.google.com/books?id=y0Pxz1L9I4EC&pg=PA441 |access-date=2010-09-13}}</ref>

<ref name="Matsuki1999">{{cite journal |author=Matsuki A |title=A bibliographical study on Shutei Nakagawa's "Mayaku-ko" (a collection of anesthetics and analgesics)--a comparism of four manuscripts |journal=Nihon Ishigaku Zasshi |volume=45 |issue=4 |date=December 1999 |pages=585–99 |language=ja |issn=0549-3323 |pmid=11624281 |url=http://sciencelinks.jp/j-east/article/200004/000020000400A0121859.php |access-date=2010-09-13 |url-status=dead |archive-url=https://web.archive.org/web/20120313120037/http://sciencelinks.jp/j-east/article/200004/000020000400A0121859.php |archive-date=13 March 2012}}</ref>

<ref name="Matsuki2000">{{cite journal |author=Matsuki A |title=New studies on the history of anesthesiology—a new study on Seishū Hanaoka's "Nyugan Ckiken Roku" (a surgical experience with breast cancer) |journal=Masui |volume=49 |issue=9 |date=September 2000 |pages=1038–43 |issn=0021-4892 |pmid=11025965 |url=http://www.biomedsearch.com/nih/New-studies-history-anesthesiology-new/11025965.html |access-date=2010-09-13}}</ref>

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<ref name="Neligan1927">{{cite journal |last1=Evans |first1=TC |title=The opium question, with special reference to Persia (book review) |journal=Transactions of the Royal Society of Tropical Medicine and Hygiene |volume=21 |pages=339–340 |year=1928 |issue=4 |doi=10.1016/S0035-9203(28)90031-0 |url=http://www.tropicalmedandhygienejrnl.net/article/S0035-9203(28)90031-0/abstract |access-date=2010-09-18 |quote=The earliest known mention of the poppy is in the language of the Sumerians, a non-Semitic people who descended from the uplands of Central Asia into Southern Mesopotamia....}}{{Dead link|date=November 2018 |bot=InternetArchiveBot |fix-attempted=yes}}</ref>

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<ref name="Gale1932">{{cite journal |last1=Gale |first1=J |last2=Waters |first2=R |title=Closed endobronchial anesthesia in thoracic surgery: preliminary report |journal=Anesthesia and Analgesia |volume=11 |issue=6 |date=1932 |pages=283–288 |doi=10.1213/00000539-193201000-00049|doi-access=free }}</ref>

<ref name="Greenblatt2014">{{cite journal |last1=Greenblatt |first1=E |last2=Butler |first2=J |last3=Venegas |first3=J |last4=Winkler |first4=T |title=Pendelluft in the bronchial tree |journal=American Journal of Physiology. Heart and Circulatory Physiology |volume=117 |issue=9 |date=2014 |pages=979–988 |pmid=25170072 |pmc=4217048 |doi=10.1152/japplphysiol.00466.2014}}</ref>

<ref name="Raventos1956">{{cite journal |last1=Raventos |first1=J |last2=Goodall |first2=R |title=The Action of Fluothane-A New Volatile Anaesthetic |journal=British Journal of Pharmacology and Chemotherapy |volume=11 |issue=4 |date=1956 |pages=394–410 |pmid=13383118 |pmc=1510559 |doi=10.1111/j.1476-5381.1956.tb00007.x}}</ref>

}}

==Further reading==
* {{cite journal |last=Goldsmith |first=WM |title=Trepanation and the 'CatlinMark' |jstor=275576 |journal=American Antiquity |volume=10 |issue=4 |pages=348–52 |year=1945 |s2cid=163518652 |doi=10.2307/275576 |url=https://scholarworks.uni.edu/pias/vol49/iss1/106}}
* {{cite journal |last=Guerra Doce |first=E |title=Evidencias del consumo de drogas en Europa durante la Prehistoria |language=es |journal=Trastornos Adictivos |volume=8 |issue=1 |pages=53–61 |year=2006 |doi=10.1016/S1575-0973(06)75106-6 |url=http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.fulltext?pident=13087278 |access-date=2010-11-14 |url-status=dead |archive-url=https://web.archive.org/web/20080515210321/http://db.doyma.es/cgi-bin/wdbcgi.exe/doyma/mrevista.fulltext?pident=13087278 |archive-date=15 May 2008}}
* {{cite book |last=Gurlt |first=EJ |author-link=Ernst Julius Gurlt |title=Geschichte der Chirurgie und ihrer Ausübung |volume=1 |chapter=VI: Volkschirurgie in Japan in alter und neuerer |page=83 |publisher=Verlag von August Hirschwald |location=Berlin |language=de |year=1898 |chapter-url=https://archive.org/details/geschichtederchi01gurl |access-date=2010-11-14}}
* {{cite journal |last=Hrdlicka |first=A |title=Trepanation among prehistoric people, especially in America |journal=Ciba Foundation Symposium |volume=1 |issue=6 |pages=170–7 |year=1939}}
* {{cite journal |last=Matsuki |first=A |title=A brief history of the biographical study of Seishu Hanaoka |journal=Nihon Ishigaku Zasshi |volume=51 |issue=3 |pages=355–84 |year=2005 |language=ja |issn=0549-3323 |pmid=16450478 |url=http://medical-journals.healia.com/doc/16450478/A-brief-history-of-biographical-Seishu-Hanaoka |access-date=2010-11-14}}
* {{cite journal |last=Matsuki |first=A |title=Why did Hanaoka's Method of Anesthesia Decay Rapidly at the End of the Edo Period? |journal=Nihon Ishigaku Zasshi |volume=52 |issue=1 |pages=40–1 |year=2006 |language=ja |issn=0549-3323}}
* {{cite journal |last=Ruffer |first=MA |title=Studies in paleopathology. Some recent researches on prehistoric trephining |journal=Journal of Pathology and Bacteriology |volume=22 |pages=90–104 |year=1918 |doi=10.1002/path.1700220109 |url=https://zenodo.org/record/1427748}}
* {{cite book |title=Smithsonian Annual Report of the Board of Regents, 1957 |chapter=Stone Age skull surgery. A general review with emphasis on the New World |pages=469–91 |last=Stewart |first=TD |year=1958}}
* Arashiro Toshiaki, ''Ryukyu-Okinawa Rekishi Jinbutsuden'', Okinawajijishuppan, 2006 p66 {{ISBN|978-4-903042-04-6}}
* "Reevaluation of surgical achievements by Tokumei Takamine". Matsuki A. Masui. November 2000; '''49'''(11):1285-9. Japanese.{{full citation needed|date=November 2016|reason=journal is missing}}
* "The secret anesthetic used in the repair of a hare-lip performed by Tokumei Takamine in Ryukyu". Matsuki A. ''Nippon Ishigaku Zasshi''. October 1985 '''31'''(4):463-89. Japanese.

==External links==
* [http://www.woodlibrarymuseum.org Wood Library-Museum of Anesthesiology] The most comprehensive educational, scientific and archival resources in anesthesiology.
* [http://www.chm.bris.ac.uk/motm/chloroform/chloroformh.htm "Chloroform: ''The molecular lifesaver''"] An article at University of Bristol providing interesting facts about chloroform.
* [https://web.archive.org/web/20040515001721/http://www.anzca.edu.au/publications/profdocs/profstandards/PS18_2000.htm Australian & New Zealand College of Anaesthetists Monitoring Standard]
* [https://web.archive.org/web/20051219095333/http://www.rcoa.ac.uk/index.asp?PageID=69 Royal College of Anaesthetists Patient Information page]
* [https://web.archive.org/web/20100728085207/http://archive.nlm.nih.gov/proj/ttp/flash/hanaoka/hanaoka.html ''Turning the Pages'']: a virtual reconstruction of Hanaoka's ''Surgical Casebook'', c. 1825. From the [[U.S. National Library of Medicine]]
* {{in lang|de}} [https://web.archive.org/web/20121114204957/http://www-user.uni-bremen.de/~d02q/index.html Die Geschichte der Anästhesie].
* [http://www.katedraanest.cm-uj.krakow.pl/download/downloads/Anestezja.ppt "Anesthesia as a specialty: Past, present and future"] Presentation by Prof. Janusz Andres.<!-- Much can be derived from this source after adding proper references -->

{{History of medicine}}

[[Category:General anesthetics]]
[[Category:History of anesthesia|General anesthesia]]
[[Category:Drug discovery]]