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Halothane
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==Side effects== Side effects include [[Heart arrhythmia|irregular heartbeat]], [[respiratory depression]], and [[hepatotoxicity]].<ref name=WHO2008/> It appears to be safe in [[porphyria]].<ref name="Porphyrias"/> It is unclear whether use during [[pregnancy]] is harmful to the baby, and it is not generally recommended for use during a [[cesarean section|C-section]].<ref name=Pro2005/> In rare cases, repeated exposure to halothane in adults was noted to result in severe [[liver]] injury. This occurred in about one in 10,000 exposures. The resulting syndrome was referred to as halothane [[hepatitis]], immunoallergic in origin,<ref>{{cite book | vauthors = Habibollahi P, Mahboobi N, Esmaeili S, Safari S, Dabbagh A, Alavian SM | title = Halothane | series = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet] | date= January 2018 | publisher = National Institute of Diabetes and Digestive and Kidney Diseases | pmid=31643481 | url=https://www.ncbi.nlm.nih.gov/books/NBK548151/ |id=NBK548151}}</ref> and is thought to result from the metabolism of halothane to [[trifluoroacetic acid]] via oxidative reactions in the liver. About 20% of inhaled halothane is metabolized by the liver and these products are excreted in the urine. The hepatitis syndrome had a mortality rate of 30% to 70%.<ref>{{cite journal | vauthors = Wark H, Earl J, Chau DD, Overton J | title = Halothane metabolism in children | journal = British Journal of Anaesthesia | volume = 64 | issue = 4 | pages = 474β481 | date = April 1990 | pmid = 2334622 | doi = 10.1093/bja/64.4.474 | doi-access = free }}</ref> Concern for hepatitis resulted in a dramatic reduction in the use of halothane for adults and it was replaced in the 1980s by [[enflurane]] and [[isoflurane]].<ref name = "Gyorfi_1997">{{cite book | vauthors = Gyorfi MJ, Kim PY | title = Halothane Toxicity |date=2022 |url= http://www.ncbi.nlm.nih.gov/books/NBK545281/ |id=NBK545281 |series =StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31424865 }}</ref><ref>{{Cite journal | vauthors = Hankins DC, Kharasch ED |date=9 May 1997 |title=Determination of the halothane metabolites trifluoroacetic acid and bromide in plasma and urine by ion chromatography |journal=Journal of Chromatography B: Biomedical Sciences and Applications |volume=692 |issue=2 |pages=413β8 |doi=10.1016/S0378-4347(96)00527-0 |pmid=9188831 |issn=0378-4347}}</ref> By 2005, the most common volatile anesthetics used were [[isoflurane]], [[sevoflurane]], and [[desflurane]]. Since the risk of halothane hepatitis in children was substantially lower than in adults, halothane continued to be used in pediatrics in the 1990s as it was especially useful for inhalation induction of anesthesia.<ref>{{cite journal | vauthors = Okuno T, Koutsogiannaki S, Hou L, Bu W, Ohto U, Eckenhoff RG, Yokomizo T, Yuki K | title = Volatile anesthetics isoflurane and sevoflurane directly target and attenuate Toll-like receptor 4 system | journal = FASEB Journal | volume = 33 | issue = 12 | pages = 14528β41 | date = December 2019 | pmid = 31675483 | pmc = 6894077 | doi = 10.1096/fj.201901570R | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sakai EM, Connolly LA, Klauck JA | title = Inhalation anesthesiology and volatile liquid anesthetics: focus on isoflurane, desflurane, and sevoflurane | journal = Pharmacotherapy | volume = 25 | issue = 12 | pages = 1773β88 | date = December 2005 | pmid = 16305297 | doi = 10.1592/phco.2005.25.12.1773 | s2cid = 40873242 }}</ref> However, by 2000, sevoflurane, excellent for inhalation induction, had largely replaced the use of halothane in children.<ref>{{cite journal | vauthors = Patel SS, Goa KL | title = Sevoflurane. A review of its pharmacodynamic and pharmacokinetic properties and its clinical use in general anaesthesia | journal = Drugs | volume = 51 | issue = 4 | pages = 658β700 | date = April 1996 | pmid = 8706599 | doi = 10.2165/00003495-199651040-00009 | s2cid = 265731583 }}</ref> Halothane sensitises the heart to catecholamines, so it is liable to cause cardiac arrhythmia, occasionally fatal, particularly if [[hypercapnia]] has been allowed to develop. This seems to be especially problematic in dental anesthesia.<ref>{{cite journal | vauthors = Paris ST, Cafferkey M, Tarling M, Hancock P, Yate PM, Flynn PJ | title = Comparison of sevoflurane and halothane for outpatient dental anaesthesia in children | journal = British Journal of Anaesthesia | volume = 79 | issue = 3 | pages = 280β4 | date = September 1997 | pmid = 9389840 | doi = 10.1093/bja/79.3.280 | doi-access = free }}</ref> Like all the potent inhalational anaesthetic agents, it is a potent trigger for [[malignant hyperthermia]].<ref name=WHO2008/> Similarly, in common with the other potent inhalational agents, it relaxes uterine smooth muscle and this may increase blood loss during delivery or termination of pregnancy.<ref>{{cite journal | vauthors = Satuito M, Tom J | title = Potent Inhalational Anesthetics for Dentistry | journal = Anesthesia Progress | volume = 63 | issue = 1 | pages = 42β8; quiz 49 | year = 2016 | pmid = 26866411 | pmc = 4751520 | doi = 10.2344/0003-3006-63.1.42 }}</ref> === Occupational safety === People can be exposed to halothane in the workplace by breathing it in as waste anaesthetic gas, skin contact, eye contact, or swallowing it.<ref>{{Cite journal |year=1999 |title=Common Name: Halothene |url=https://nj.gov/health/eoh/rtkweb/documents/fs/0969.pdf |journal=Hazardous Substance Fact Sheet |type=PDF |volume=969 |issue=1 |via=[[New Jersey Department of Health|New Jersey Department of Health and Senior Services]]}}</ref> The [[National Institute for Occupational Safety and Health]] (NIOSH) has set a [[recommended exposure limit]] (REL) of 2 ppm (16.2 mg/m<sup>3</sup>) over 60 minutes.<ref>{{Cite web |title =Halothane |work=NIOSH Pocket Guide to Chemical Hazards |url = https://www.cdc.gov/niosh/npg/npgd0310.html|publisher=(NIOSH) National Institute for Occupational Safety and Health, Centers for Disease Control |access-date = 3 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151208104932/http://www.cdc.gov/niosh/npg/npgd0310.html|archive-date = 8 December 2015}}</ref>
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