Editing Chloroform (section)

===Anaesthetic===
[[File:Chickamauga 2009, Chloroform.jpg|thumb|Antique bottles of chloroform]]
Chloroform is a powerful [[general anesthetic]], [[euphoriant]], [[anxiolytic]], and [[sedative]] when inhaled or ingested. The [[anaesthetic]] qualities of chloroform were first described in 1842 in a thesis by [[Robert Mortimer Glover]], which won the Gold Medal of the [[Harveian Society]] for that year.<ref name="Chloroform History">{{cite journal |last1=Perkins-McVey |first1=Matthew |title="A new order of poisonous substances": revisiting Robert M. Glover's dissertation on the physiological effects of bromine, chlorine, and iodine compounds |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |date=10 November 2023 |volume=397 |issue=5 |pages=3343–3350 |doi=10.1007/s00210-023-02820-y |url=https://www.researchgate.net/publication/375556103 |access-date=27 January 2024|doi-access=free |pmid=37947840 }}</ref><ref>{{cite journal |last1=Glover |first1=Robert M. |title=On the Physiological and Medicinal Properties of Bromine and Its Compounds; Also on the Analogies between the Physiological and Medicinal Properties of These Bodies, and Those of Chlorine and Iodine, with Their Correspondent Compounds; Being the Harveian Prize Essay for 1842. |journal=Edinburgh Medical and Surgical Journal |date=1 October 1842 |volume=58 |issue=153 |pages=335–364 |pmid=30330609 |pmc=5789197 }}</ref> Glover also undertook practical experiments on dogs to prove his theories, refined his theories, and presented them in his doctoral thesis at the [[University of Edinburgh]] in the summer of 1847, identifying anaesthetizing halogenous compounds as a "new order of poisonous substances".<ref name="Chloroform History" />

The Scottish [[obstetrics|obstetrician]] [[James Young Simpson]] was one of those examiners required to read the thesis, but later claimed to have never read it and to have come to his own conclusions independently.<ref name="Chloroform History" /> Perkins-McVey, among others, have raised doubts about the credibility of Simpson's claim, noting that Simpson's publications on the subject in 1847 explicitly echo Glover's and, being one of the thesis examiners, Simpson was likely aware of the content of Glover's study, even if he skirted his duties as an examiner.<ref name="Chloroform History" /> In 1847 and 1848, Glover would pen a series of heated letters accusing Simpson of stealing his discovery, which had already earned Simpson considerable notoriety.<ref name="Chloroform History" /> Whatever the source of his inspiration, on 4 November 1847, Simpson argued that he had discovered the anaesthetic qualities of chloroform in humans. He and two colleagues entertained themselves by trying the effects of various substances, and thus revealed the potential for chloroform in medical procedures.<ref name="Gordon2002">{{cite book|last=Gordon|first=H. Laing|title=Sir James Young Simpson and Chloroform (1811–1870)|url=https://books.google.com/books?id=pYer05UwKBYC&pg=PA106|date=November 2002|publisher=Minerva Group|isbn=978-1-4102-0291-8|pages=106–109|access-date=5 January 2016|archive-date=6 May 2016|archive-url=https://web.archive.org/web/20160506214333/https://books.google.com/books?id=pYer05UwKBYC&pg=PA106|url-status=live}}</ref>
[[File:James Young Simpson chloroform.png|thumb|An illustration depicting James Young Simpson and his friends found unconscious.]]
A few days later, during the course of a dental procedure in [[Edinburgh]], [[Francis Brodie Imlach]] became the first person to use chloroform on a patient in a clinical context.<ref>{{cite web |last=Dingwall |date=April 2004 |url=http://historyofdentistry.co.uk/index_htm_files/2004Apr2.pdf |title=A pioneering history: dentistry and the Royal College of Surgeons of Edinburgh |website=historyofdentistry.co.uk  |archive-url=https://web.archive.org/web/20130201191323/http://historyofdentistry.co.uk/index_htm_files/2004Apr2.pdf |archive-date=1 February 2013}}</ref>

In May 1848, [[Robert Halliday Gunning]] made a presentation to the Medico-Chirurgical Society of Edinburgh following a series of laboratory [[Domestic rabbit#Experimentation|experiments on rabbits]] that confirmed Glover's findings and also refuted Simpson's claims of originality. The laboratory experiments that proved the dangers of chloroform were largely ignored.<ref>{{cite journal |url=https://www.royalsoced.org.uk/cms/files/research_awards/prizes/prize_lists/gunning_victoria_history.pdf |title=Robert Halliday Gunning and the Victoria Jubilee Prizes |year=2003 |access-date=2016-08-18  |archive-url=https://web.archive.org/web/20160822105053/https://www.royalsoced.org.uk/cms/files/research_awards/prizes/prize_lists/gunning_victoria_history.pdf |archive-date=22 August 2016 |doi=10.1177/003693300304800209 |last1=Baillie |first1=T. W. |journal=Scottish Medical Journal |volume=48 |issue=2 |pages=54–57 |pmid=12774598 |s2cid=10998512 }}</ref>

The use of chloroform during [[surgery]] expanded rapidly in Europe; for instance in the 1850s chloroform was used by the physician [[John Snow]] during the births of [[Queen Victoria]]'s last two children [[Prince Leopold, Duke of Albany|Leopold]] and [[Princess Beatrice of the United Kingdom|Beatrice]].<ref>{{cite web |url=http://www.ph.ucla.edu/epi/snow/victoria.html |title=Anesthesia and Queen Victoria |website=ph.ucla.edu |access-date=13 August 2012 |url-status=live |archive-url=https://web.archive.org/web/20120716005223/http://www.ph.ucla.edu/epi/snow/victoria.html |archive-date=16 July 2012}}</ref> In the United States, chloroform began to replace [[Diethyl ether|ether]] as an anesthetic at the beginning of the 20th century;<ref name="Chloroform History in U.S.">{{cite journal |last1=Wawersik |first1=J |title=[History of chloroform anesthesia]. |journal=Anaesthesiologie und Reanimation |date=1997 |volume=22 |issue=6 |pages=144-52 |pmid=9487785 |url=https://pubmed.ncbi.nlm.nih.gov/9487785/}}</ref> it was abandoned in favor of ether on discovery of its toxicity, especially its tendency to cause fatal [[cardiac arrhythmia|cardiac arrhythmias]] analogous to what is now termed "[[Intoxicative inhalant#Sudden sniffing death syndrome|sudden sniffer's death]]". Some people used chloroform as a recreational drug or to attempt suicide.<ref>{{cite journal|last=Martin|first=William|title=A Case of Chloroform Poisoning; Recovery|journal=British Medical Journal|date=3 July 1886|volume=2|issue=1331|pages=16–17|pmc=2257365|doi=10.1136/bmj.2.1331.16-a|pmid=20751619}}</ref> One possible mechanism of action of chloroform is that it increases the movement of [[potassium]] ions through certain types of [[potassium channel]]s in [[nerve cells]].<ref>{{Cite journal|last1 = Patel|first1 = Amanda J.|last2 = Honoré|first2 = Eric|last3 = Lesage|first3 = Florian|last4 = Fink|first4 = Michel|last5 = Romey|first5 = Georges|last6 = Lazdunski|first6 = Michel|date = May 1999|title = Inhalational anesthetics activate two-pore-domain background K<sup>+</sup> channels|journal = Nature Neuroscience|volume = 2|pages = 422–426|doi = 10.1038/8084|pmid = 10321245|issue = 5|s2cid = 23092576}}</ref> Chloroform could also be mixed with other anesthetic agents such as ether to make C.E. mixture,<ref name="Chloroform & Ether">{{cite journal |last1=von Hintzenstern |first1=U. |last2=Schwarz |first2=W. |title=Frühe Erlanger Beiträge zur Theorie und Praxis der Ather- und Chloroformnnarkose |journal=Der Anaesthesist |date=1 February 1996 |volume=45 |issue=2 |pages=131–139 |doi=10.1007/s001010050247 |pmid=8720885 |url=https://pubmed.ncbi.nlm.nih.gov/8720885/ |access-date=17 March 2025 |trans-title=Early contributions from Erlangen to the theory and practice of ether and chloroform anesthesia. 1. Heyfelder's clinical trial with ether and chloroform |language=de}}</ref> or ether and [[Ethanol|alcohol]] to make [[A.C.E. mixture]].<ref name="Alcohol, Chloroform & Ether">{{cite journal |title=An Experience with the New Anæsthetic-Chloroform, Ether and Absolute Alcohol. |journal=The Independent practitioner |date=February 1883 |volume=4 |issue=2 |pages=97-100 |pmid=37826124 |url=https://pubmed.ncbi.nlm.nih.gov/37826124/ |access-date=17 March 2025 |language=English |pmc=10072673}}</ref><ref name="ACE Mixture">{{cite journal |last1=Shah |first1=Shrey P. |last2=Bause |first2=George S. |title=From ACE to ACENO: How America's Munson added Harley's British mixture to nitrous oxide |journal=Journal of Anesthesia History |date=September 2020 |volume=6 |issue=3 |pages=168–169 |doi=10.1016/j.janh.2020.07.006 |pmid=32921491 |url=https://pubmed.ncbi.nlm.nih.gov/32921491/ |access-date=17 March 2025}}</ref> 

In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anaesthetic.<ref>{{cite journal|title=An Unexplained Death: Hannah Greener and Chloroform |last1=Knight |first1=Paul R. III |last2=Bacon |first2=Douglas R. |s2cid=12865865 | year=2002 |volume = 96 |issue = 5 |journal=Anesthesiology|doi=10.1097/00000542-200205000-00030|pages=1250–1253|pmid=11981167|doi-access=free }}</ref> Her autopsy establishing the cause of death was undertaken by [[John Fife (surgeon)|John Fife]] assisted by [[Robert Mortimer Glover]].<ref name=pdf1/> A number of physically fit patients died after inhaling it. In 1848, however, John Snow developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.<ref>{{cite book|last1 = Snow|first1 = John|year = 1858|title = On Chloroform and Other Anaesthetics and Their Action and Administration|pages = 82–85|url = https://archive.org/stream/onchloroformothe1858snow#page/82/mode/2up/search/inhaler|url-status = live|archive-url = http://archive.wikiwix.com/cache/20151123021418/https://archive.org/stream/onchloroformothe1858snow#page/82/mode/2up/search/inhaler|archive-date = 23 November 2015|publisher = London : John Churchill}}</ref>

The opponents and supporters of chloroform disagreed on the question of whether the medical complications were due to respiratory disturbance or whether chloroform had a specific effect on the heart. Between 1864 and 1910, numerous commissions in Britain studied chloroform but failed to come to any clear conclusions. It was only in 1911 that Levy proved in experiments with animals that chloroform can cause ventricular fibrillation.<ref name="Chloroform ventricular fibrillation">{{cite journal |last1=Hutcheon |first1=D. E. |title=SUSCEPTIBILITY TO VENTRICULAR FIBRILLATION DURING CHLOROFORM AND CYCLOPROPANE ANAESTHESIA |journal=British Journal of Pharmacology and Chemotherapy |date=March 1951 |volume=6 |issue=1 |pages=31–34 |doi=10.1111/j.1476-5381.1951.tb00617.x |pmid=14821299 |url=https://pubmed.ncbi.nlm.nih.gov/37826124/ |access-date=17 March 2025 |language=English |pmc=1509204}}</ref> Despite this, between 1865 and 1920, chloroform was used in 80 to 95% of all narcoses performed in the UK and German-speaking countries. In Germany, comprehensive surveys of the fatality rate during anaesthesia were made by Gurlt between 1890 and 1897.<ref name="Chloroform History in U.S." /> At the same time in the UK the medical journal ''[[The Lancet]]'' carried out a questionnaire survey<ref>{{Cite journal |last=Anonymous. |date=1890 |title=The Lancet Inquiry into the Mortality Under Anaesthetics. |journal=Lancet |volume=145 |issue=3472 |pages=612–13}}</ref> and compiled a report detailing numerous adverse reactions to anesthetics, including chloroform.<ref>{{Cite journal |last=Anonymous. |date=1893 |title=Report of The Lancet Commission appointed to investigate the subject of the administration of chloroform and other anesthetics from a clinical standpoint. |journal=Lancet |volume=141 |issue=3629 |pages=629–38}}</ref> In 1934, Killian gathered all the statistics compiled until then and found that the chances of suffering fatal complications under ether were between 1:14,000 and 1:28,000, whereas with chloroform the chances were between 1:3,000 and 1:6,000.<ref name="Chloroform History in U.S." /> The rise of gas anaesthesia using [[nitrous oxide]], improved equipment for administering anesthetics, and the discovery of [[hexobarbital]] in 1932 led to the gradual decline of chloroform narcosis.<ref>{{cite journal | pmid = 9487785 | volume=22 | issue=6 | title=History of chloroform anesthesia | year=1997 | journal=Anesthesiology and Reanimation | pages=144–152 | last= Wawersik |first=J.}}</ref>

The latest reported anaesthetic use of chloroform in the Western world dates to 1987, when the last doctor who used it retired, about 140 years after its first use.<ref>{{cite book|last=Stratmann|first=Linda|date=2003|title=Chloroform: The Quest for Oblivion|location=Stroud|publisher=Sutton Publishing|isbn=978-0-7524-9931-4}}</ref>