Editing Inhalational anesthetic

{{Short description|Volatile or gaseous anesthetic compound delivered by inhalation}}
[[File:Fluranebottles.jpg|thumb|upright=1.5|Bottles of [[sevoflurane]], [[isoflurane]], [[enflurane]], and [[desflurane]], the common fluorinated [[ether]] anesthetics used in clinical practice. These agents are colour-coded for safety purposes. Note the special fitting for desflurane, which [[Boiling point|boils]] at [[Standard temperature and pressure|room temperature]].]]

An '''inhalational anesthetic''' is a chemical compound possessing [[general anesthetic]] properties that is delivered via inhalation. They are administered through a face mask, [[laryngeal mask airway]] or [[tracheal tube]] connected to an [[anaesthetic vaporiser|anesthetic vaporiser]] and an [[anesthetic machine|anesthetic delivery system]]. Agents of significant contemporary clinical interest include [[Volatility (chemistry)|volatile]] anesthetic agents such as [[isoflurane]], [[sevoflurane]] and [[desflurane]], as well as certain anesthetic gases such as [[nitrous oxide]] and [[xenon]].

==List of inhalational anaesthetic agents==

===Currently-used agents===
* [[Desflurane]]
* [[Isoflurane]]
* [[Nitrous oxide]]
* [[Sevoflurane]]
* [[Xenon]]

===Previously-used agents===
Although some of these are still used in clinical practice and in research, the following anaesthetic agents are primarily of historical interest in [[Developed country|developed countries]]:

* [[Acetylene]]
* [[Chloroethane|Chloroethane (ethyl chloride)]]
* [[Chloroform]]
* [[Cryofluorane]]
* [[Cyclopropane]]
* [[Diethyl ether]]
* [[Divinyl ether]]
* [[Enflurane]]
* [[Ethylene]]
* [[Fluroxene]]
* [[Halothane]] (still widely used in the [[developing world]] and is on the [[WHO Model List of Essential Medicines]])
* [[Methoxyflurane]] (still used currently as an [[analgesic]])
* [[Methoxypropane]]
* [[Trichloroethylene]]
* [[Vinyl chloride]]<ref name="pmid572591">{{cite journal |vauthors=Tamburro CH |title=Health effects of vinyl chloride |journal=Texas Reports on Biology and Medicine |volume=37 |pages=126–44, 146–51 |date=1978 |pmid=572591}}</ref><ref name="pmid20255056">{{cite journal |vauthors=Oster RH, Carr CJ |title=Anesthesia; narcosis with vinyl chloride |journal=Anesthesiology |volume=8 |issue=4 |pages=359–61 |date=July 1947 |pmid=20255056 |doi=10.1097/00000542-194707000-00003 |s2cid=73229069 |url=https://pubs.asahq.org/anesthesiology/article/8/4/359/34257/ANESTHESIA-XXVII-NARCOSIS-WITH-VINYL-CHLORIDE|doi-access=free }}</ref>

===Never-marketed agents===
* [[Aliflurane]]
* [[Halopropane]]
* [[Norflurane]]
* [[Roflurane]]
* [[Synthane]]
* [[Teflurane]]

==Volatile anaesthetics==

Volatile anaesthetic agents share the property of being liquid at room temperature, but evaporating easily for administration by inhalation. The volatile anesthetics used in the developed world today include: Desflurane, isoflurane and sevoflurane. Other agents widely used in the past include ether, chloroform, enflurane, halothane, methoxyflurane. All of these agents share the property of being quite [[Hydrophobe|hydrophobic]] (i.e., as liquids, they are not freely [[Miscibility|miscible]] with water, and as gases they dissolve in oils better than in water).<ref>{{cite web | url=https://www.ncbi.nlm.nih.gov/books/NBK537013/ | pmid=30725698 | year=2022 | last1=Clar | first1=D. T. | last2=Patel | first2=S. | last3=Richards | first3=J. R. | title=Anesthetic Gases | publisher=StatPearls }}</ref>

The ideal volatile anaesthetic agent offers smooth and reliable induction and maintenance of [[general anaesthesia]] with minimal effects on non-target [[organ (anatomy)|organ]] systems. In addition it is odorless or pleasant to inhale; safe for all ages and in pregnancy; not metabolised; rapid in onset and offset; potent; safe for exposure to [[Operating theater|operating room]] staff; and has a long [[shelf life]]. It is also cheap to manufacture; easy to transport and store; easy to administer and monitor with standard operating room equipment; stable to light, plastics, metals, [[Natural rubber|rubber]] and [[soda lime]]; and non-flammable and environmentally safe. None of the agents currently in use are ideal, although many have some of the desirable characteristics. For example, sevoflurane is pleasant to inhale and is rapid in onset and offset. It is also safe for all ages. However, it is expensive (approximately 3 to 5 times more expensive than isoflurane), and approximately half as potent as isoflurane.<ref>{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/14991199/ | pmid=14991199 | year=2004 | last1=Loscar | first1=M. | last2=Conzen | first2=P. | title=Volatile anesthetics | journal=Der Anaesthesist | volume=53 | issue=2 | pages=183–198 | doi=10.1007/s00101-003-0632-6 | s2cid=26029329 }}</ref>

==Gases==
Other gases or vapors which produce general anaesthesia by inhalation include nitrous oxide, [[Endogenous anesthetic|carbon dioxide]], cyclopropane, and xenon. These are stored in [[gas cylinder]]s and administered using [[Flow measurement|flowmeters]], rather than vaporisers. Cyclopropane is [[Explosive material|explosive]] and is no longer used for safety reasons, although otherwise it was found to be an excellent anaesthetic. Xenon is odorless (odourless) and rapid in onset, but is expensive and requires specialized equipment to administer and monitor. Nitrous oxide, even at 80% concentration, does not quite produce surgical level anaesthesia in most people at [[Atmospheric pressure#Standard atmospheric pressure|standard atmospheric pressure]], so it must be used as an adjunct anaesthetic, along with other agents.

==Hyperbaric anaesthesia==
Under [[Wiktionary:hyperbaric|hyperbaric]] conditions ([[pressure]]s above normal [[atmospheric pressure]]), other gases such as [[nitrogen]], and [[noble gas]]es such as [[argon]], [[krypton]], and xenon become anaesthetics. When inhaled at high [[partial pressure]]s (more than about 4 bar, encountered at depths below about 30 metres in [[scuba diving]]), nitrogen begins to act as an anaesthetic agent, causing [[nitrogen narcosis]].<ref>{{Cite journal|last=Fowler |first=B |author2=Ackles, KN |author3=Porlier, G  |title=Effects of inert gas narcosis on behavior—a critical review. |journal=Undersea Biomed. Res. |volume=12 |issue=4 |pages=369–402 |year=1985 |pmid=4082343 |url=http://archive.rubicon-foundation.org/3019 |archive-url=https://web.archive.org/web/20081026040357/http://archive.rubicon-foundation.org/3019 |url-status=usurped |archive-date=October 26, 2008 |access-date=2008-09-21}}</ref><ref>{{Cite journal |author1=Rogers, W. H. |author2=Moeller, G. |title=Effect of brief, repeated hyperbaric exposures on susceptibility to nitrogen narcosis |journal=Undersea Biomed. Res. |volume=16 |issue=3 |pages=227–32 |year=1989 |issn=0093-5387 |oclc=2068005 |pmid=2741255 |url=http://archive.rubicon-foundation.org/2522 |access-date=2008-09-21 |archive-url=https://web.archive.org/web/20090901020853/http://archive.rubicon-foundation.org/2522 |archive-date=2009-09-01 |url-status=usurped }}</ref> However, the [[minimum alveolar concentration]] (MAC) for nitrogen is not achieved until pressures of about 20 to 30 atm (bar) are attained.<ref>{{Cite journal|url = http://jap.physiology.org/cgi/content/abstract/78/6/2241|doi = 10.1152/jappl.1995.78.6.2241|title = Nitrogen narcosis attenuates shivering thermogenesis|year = 1995|last1 = Mekjavic|first1 = I. B.|last2 = Savic|first2 = S. A.|last3 = Eiken|first3 = O.|journal = Journal of Applied Physiology|volume = 78|issue = 6|pages = 2241–2244|pmid = 7665424|access-date = 2010-11-08|archive-date = 2008-05-21|archive-url = https://web.archive.org/web/20080521160538/http://jap.physiology.org/cgi/content/abstract/78/6/2241|url-status = dead|url-access = subscription}}</ref> Argon is slightly more than twice as anaesthetic as nitrogen per unit of partial pressure (see [[Argox (breathing gas)|argox]]). Xenon however is a usable anaesthetic at 80% concentration and normal atmospheric pressure.<ref name="Burov1999">{{cite journal |author1=Burov, NE |author2=Kornienko, Liu |author3=Makeev, GN |author4=Potapov, VN |date=November–December 1999 |title=Clinical and experimental study of xenon anesthesia |journal=Anesteziol Reanimatol |issue=6 |pages=56–60 |pmid=11452771 |url=http://www.general-anaesthesia.com/xenon-anaesthesia.html |access-date=2008-11-03 }}</ref>

==Endogenous analogous==
[[Endogenous anesthetic|Endogenous analogs]] of inhaled anesthetics are compounds that the body produces and that have the properties and similar mode of action of inhaled anesthetics.<ref>{{cite journal |last1=Lerner |first1=Richard A. |title=A hypothesis about the endogenous analogue of general anesthesia |journal=Proceedings of the National Academy of Sciences |date=9 December 1997 |volume=94 |issue=25 |pages=13375–13377 |doi=10.1073/pnas.94.25.13375 |pmid=9391028 |pmc=33784 |bibcode=1997PNAS...9413375L |doi-access=free }}</ref> Among the gases in the human body, [[carbon dioxide]] is among the most abundant and produces anesthesia from insects to humans.<ref>{{cite journal |last1=Nilson |first1=Theresa L. |last2=Sinclair |first2=Brent J. |last3=Roberts |first3=Stephen P. |title=The effects of carbon dioxide anesthesia and anoxia on rapid cold-hardening and chill coma recovery in Drosophila melanogaster |journal=Journal of Insect Physiology |date=October 2006 |volume=52 |issue=10 |pages=1027–1033 |doi=10.1016/j.jinsphys.2006.07.001|pmid=16996534 |pmc=2048540 }}</ref> {{chem2|CO2}} anesthesia was first demonstrated to the king of France in the early 1800s by [[Henry Hill Hickman]]. Initially {{chem2|CO2}} was thought to work through anoxia, but in the early 1900, increased {{chem2|CO2}} in the lung showed a dramatic increase oxygenation of the brain disproving the anoxia argument.<ref>{{cite journal |last1=Moriarty |first1=John D. |title=Evaluation of Carbon Dioxide Inhalation Therapy |journal=American Journal of Psychiatry |date=April 1954 |volume=110 |issue=10 |pages=765–769 |doi=10.1176/ajp.110.10.765|pmid=13138755 }}</ref> Prior to the development of modern anesthetics, {{chem2|CO2}} was used extensively by psychiatrists in a treatment called carbon dioxide inhalation therapy.<ref>{{cite journal |doi=10.1176/ajp.110.10.765 |title=Evaluation of Carbon Dioxide Inhalation Therapy |date=1954 |last1=Moriarty |first1=John D. |journal=American Journal of Psychiatry |volume=110 |issue=10 |pages=765–769 |pmid=13138755 }}</ref>

==Neurological theories of action==
{{Update|Important research from Scripps Research misses here.|date=October 2021}}

{{Main|Theories of general anaesthetic action}}

The full mechanism of action of volatile anaesthetic agents is unknown and has been the subject of intense debate. "Anesthetics have been used for 160 years, and how they work is one of the great mysteries of neuroscience," says anaesthesiologist James Sonner of the [[University of California]], San Francisco. Anaesthesia research "has been for a long time a science of untestable hypotheses," notes Neil L. Harrison of [[Cornell University]].<ref name="Comfortably Numb">John Travis, "Comfortably Numb, Anesthetics are slowly giving up the secrets of how they work," Science News. (July 3rd 2004). [http://www.sciencenews.org/articles/20040703/bob8.asp].</ref>

"Most of the injectable anesthetics appear to act on a single molecular target," says Sonner. "It looks like inhaled anesthetics act on multiple molecular targets. That makes it a more difficult problem to pick apart."

The possibility of anaesthesia by the inert gas [[argon]] in particular (even at 10 to 15 bar) suggests that the mechanism of action of volatile anaesthetics is an effect best described by [[physical chemistry]], and not a [[chemical bond]]ing action. However, the agent may bind to a receptor with a weak interaction. A physical interaction such as swelling of [[nerve cell]] membranes from gas solution in the [[lipid bilayer]] may be operative. Notably, the gases [[hydrogen]], [[helium]], and [[neon]] have not been found to have anaesthetic properties at any pressure. Helium at high pressures produces nervous irritation ("anti-anaesthesia"), suggesting that the anaesthetic mechanism(s) may be operated in reverse by this gas (i.e., nerve membrane compression). Also, some [[halogenated ether]]s (such as [[flurothyl]]) also possess this "anti-anaesthetic" effect, providing further evidence for this theory.

==History==
[[Paracelsus]] developed an inhalational anaesthetic in 1540.<ref name="Terrel1986">{{cite book|last=Terrell|first=RC|chapter=Future Development of Volatile Anesthetics|title=ZAK Zürich |series=Anaesthesiologie und Intensivmedizin / Anaesthesiology and Intensive Care Medicine|year=1986|volume=188|pages=87–92|doi=10.1007/978-3-642-71269-2_12|isbn=978-3-642-71269-2}} citing Fülöp-Miller R (1938) ''Triumph over pain.'' Literary Guild of America, New York.</ref> He used sweet oil of vitriol (prepared by Valerius Cordus and named ''Aether'' by Frobenius):<ref name="Terrel1986" /> used to feed fowl: “it was taken even by chickens and they fall asleep from it for a while but awaken later without harm”.<ref name="Terrel1986" /> Subsequently, about 40 years later, in 1581, Giambattista Delia Porta demonstrated the use of ether on humans although it was not employed for any type of surgical anesthesia.<ref name="Terrel1986" />

In modern medicine, Dr. [[Horace Wells]] used nitrous oxide for his own dental extraction in 1844. However his attempt to replicate these results at [[Massachusetts General Hospital]] (MGH) resulted in a partial anesthetic and was deemed a failure.

[[William T.G. Morton]] is credited with successfully demonstrating surgical anesthesia for the first time on October 16, 1846, at MGH. Following this event, the use of ether and other volatile anesthetics became widespread in Western medicine.<ref>{{cite web | url=https://www.woodlibrarymuseum.org/history-of-anesthesia/ | title=History of Anesthesia }}</ref>

After the experiments and publications by the Scottish obstetrician [[James Young Simpson]] in late 1847, [[chloroform]] became the first widespread [[halocarbon]] anaesthetic. Chloroform is a much stronger and effective anaesthetic than ether, it is non-inflammable and it did not irritate the airways, unlike ether.

First non-gaseous inhalational anaesthetics such as ether and chloroform were inhaled from a handkerchief which the liquid was poured on and allowed to evaporate. Concerns about the dosage of chloroform lead to development of various [[anaesthetic vaporiser|inhaler]]s.

==See also==
* [[A.C.E. mixture]] - a mixture of [[ethanol]], chloroform and diethyl ether
* [[Anesthetic|Anaesthetic]]
* [[Concentration effect]]
* [[Second gas effect]]

==References==
{{Reflist|30em}}

{{General anesthetics}}
{{GABAAR PAMs}}
{{Glutamatergics}}
{{Authority control}}

[[Category:General anesthetics]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:NMDA receptor antagonists]]