Desflurane

{{Drugbox

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| image = (RS)-Desfluran Structural Formula V1.svg

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| image2 = Desflurane-3D-balls.png

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| pronounce = des-FLOO-rane

| tradename = Suprane

| Drugs.com = {{drugs.com|cons|desflurane-inhalation-oral-nebulization}}

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| DailyMedID = Desflurane

| pregnancy_AU = B3

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| routes_of_administration = Inhalation

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| ATC_prefix = N01

| ATC_suffix = AB07

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| legal_AU = S4

| legal_AU_comment =

| legal_BR = C1

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=Diário Oficial da União |language=pt-BR |publication-date=4 April 2023}}

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| legal_US = Rx-only

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| bioavailability =

| protein_bound =

| metabolism = Not metabolized

| elimination_half-life = Elimination dependent on minute ventilation

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 57041-67-5

| PubChem = 42113

| IUPHAR_ligand = 7156

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01189

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 38403

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = CRS35BZ94Q

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| KEGG = D00546

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 4445

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1200733

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| synonyms =

| IUPAC_name = 2-(difluoromethoxy)-1,1,1,2-tetrafluoroethane

| C=3 | H=2 | F=6 | O=1

| SMILES = FC(F)(F)C(F)OC(F)F

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C3H2F6O/c4-1(3(7,8)9)10-2(5)6/h1-2H

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| StdInChIKey = DPYMFVXJLLWWEU-UHFFFAOYSA-N

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Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane, and isoflurane, it is a racemic mixture of (R) and (S) optical isomers (enantiomers). Together with sevoflurane, it is gradually replacing isoflurane for human use, except in economically undeveloped areas, where its high cost precludes its use. It has the most rapid onset and offset of the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood.

Some drawbacks of desflurane are its low potency, its pungency and its high cost (though at low flow fresh gas rates, the cost difference between desflurane and isoflurane appears to be insignificant{{cite thesis | vauthors = Varkey JK |title=Cost Analysis of Desflurane and Sevoflurane: An Integrative Review and Implementation Project Introducing the Volatile Anesthetic Cost Calculator |date= October 2012 | degree = Doctor of Nursing Practice | publisher = Texas Christian University |url=https://docplayer.net/6165775-Cost-analysis-of-desflurane-and-sevoflurane-an-integrative-review-and-implementation-project.html}}). It may cause tachycardia and airway irritability when administered at concentrations greater than 10% by volume. Due to this airway irritability, desflurane is infrequently used to induce anesthesia via inhalation techniques.

Though it vaporizes very readily, it is a liquid at room temperature. Anaesthetic machines are fitted with a specialized anaesthetic vaporiser unit that heats liquid desflurane to a constant temperature. This enables the agent to be available at a constant vapor pressure, negating the effects fluctuating ambient temperatures would otherwise have on its concentration imparted into the fresh gas flow of the anesthesia machine.

Desflurane, along with enflurane and to a lesser extent isoflurane, has been shown to react with the carbon dioxide absorbent in anesthesia circuits to produce detectable levels of carbon monoxide through degradation of the anesthetic agent. The {{CO2}} absorbent Baralyme, when dried, is most culpable for the production of carbon monoxide from desflurane degradation, although it is also seen with soda lime absorbent as well. Dry conditions in the carbon dioxide absorbent are conducive to this phenomenon, such as those resulting from high fresh gas flows.{{cite journal | vauthors = Fang ZX, Eger EI, Laster MJ, Chortkoff BS, Kandel L, Ionescu P | title = Carbon monoxide production from degradation of desflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime and Baralyme | journal = Anesthesia and Analgesia | volume = 80 | issue = 6 | pages = 1187–93 | date = June 1995 | pmid = 7762850 | doi = 10.1097/00000539-199506000-00021 | s2cid = 41150462 | doi-access = free }}

Pharmacology

{{As of|2005}} the exact mechanism of the action of general anaesthetics has not been delineated.{{cite web | vauthors = Perkins B |url=http://www.scientificamerican.com/article/how-does-anesthesia-work/ |title=How does anesthesia work? |publisher=Scientific American |date=7 February 2005 |access-date=30 June 2016}} Desflurane is known to act as a positive allosteric modulator of the GABA_A and glycine receptors,{{cite book| vauthors = Hemmings HC, Hopkins PM |title=Foundations of Anesthesia: Basic Sciences for Clinical Practice|url=https://books.google.com/books?id=xaXu1wHmENoC&pg=PA290|year=2006|publisher=Elsevier Health Sciences|isbn=0-323-03707-0|pages=290–291}}{{cite book| vauthors = Miller RD, Eriksson LI, Fleisher LA, Wiener-Kronish JP, Cohen NH, Young WL | title=Miller's Anesthesia|url=https://books.google.com/books?id=L2ckBQAAQBAJ&pg=PA624|date=20 October 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-28011-2|pages=624–}}{{Cite journal | vauthors = Nishikawa K, Harrison NL | title = The actions of sevoflurane and desflurane on the gamma-aminobutyric acid receptor type A: effects of TM2 mutations in the alpha and beta subunits | journal = Anesthesiology | volume = 99 | issue = 3 | pages = 678–684 | year = 2003 | pmid = 12960553| doi = 10.1097/00000542-200309000-00024 | s2cid = 72907404 | doi-access = free }} and as a negative allosteric modulator of the nicotinic acetylcholine receptor,{{cite book| vauthors = Reed AP, Yudkowitz FS |title=Clinical Cases in Anesthesia|url=https://books.google.com/books?id=9VVJAgAAQBAJ&pg=PA101|date=2 December 2013|publisher=Elsevier Health Sciences|isbn=978-0-323-18654-4|pages=101–}}{{cite book| vauthors = Barash P, Cullen BF, Stoelting RK, Cahalan M, Stock MC, Ortega R |title=Clinical Anesthesia | edition = 7th |url=https://books.google.com/books?id=exygUxEuxnIC&pg=PA470|date=7 February 2013|publisher=Lippincott Williams & Wilkins|isbn=978-1-4698-3027-8|pages=470–}} as well as affecting other ligand-gated ion channels.{{cite book| vauthors = Coté CJ, Lerman J, Todres ID |title=A Practice of Anesthesia for Infants and Children: Expert Consult – Online and Print|url=https://books.google.com/books?id=MAXTnQStL0cC&pg=PA499|year=2013|publisher=Elsevier Health Sciences|isbn=978-1-4377-2792-0|pages=499–}}{{cite book| veditors = Aglio LS, Lekowski RW, Urman RD |title=Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards|url=https://books.google.com/books?id=VJzWBQAAQBAJ&pg=PA128|date=8 January 2015|publisher=Cambridge University Press|isbn=978-1-107-68130-9|pages=128–}}

Stereochemistry

Desflurane medications are a racemate of two enantiomers.Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 - Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, {{ISBN|978-3-946057-10-9}}, S. 175.

class="wikitable" style="text-align:center"

class="hintergrundfarbe6"

! colspan="2"| Enantiomeres of desflurane

File:(R)-Desfluran Structural Formula V1.svg
(R)-Enantiomer

| File:(S)-Desfluran Structural Formula V1.svg
(S)-Enantiomer

Physical properties

Boiling point :	align=right\| 23.5 °C or 74.3 °F	(at 1 atm)
Density :	1.465 g/cm³	(at 20 °C)
Molecular Weight :	align=right\| 168
Vapor pressure:	align=right\| 88.5 kPa	align=right\| 672 mmHg	(at 20 °C)
	align=right\| 107 kPa	align=right\|804 mmHg	(at 24 °C)
Blood:Gas partition coefficient:	align=right\| 0.42
Oil:Gas partition coefficient :	align=right\| 19
MAC :	align=right\| 6 vol %

Physiologic effects

Desflurane induces a dose dependent reduction in blood pressure due to reduced systemic vascular resistance. However, rapid increases in desflurane may induce a transient sympathetic response secondary to catecholamine release. Even though it is highly pungent, it is still a bronchodilator. It reduces the ventilatory response to hypoxia and hypercapnia. Like sevoflurane, desflurane vasodilatory properties also cause it to increase intracranial pressure and cerebral blood flow. However, it reduces cerebral metabolic rate. It also promotes muscle relaxation and potentiate neuromuscular blockade at a greater level than sevoflurane.

{{cite book | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK537106/ | pmid=30725791 | year=2022 | vauthors = Khan J, Liu M | chapter = Desflurane | title = StatPearls | location = Treasure Island (FL) | publisher = StatPearls Publishing }}

Contraindications

It is contraindicated for induction of general anesthesia in the non-intubated pediatric population due to the high risk of laryngospasm. It should not be used in patients with known or suspected susceptibility to malignant hyperthermia. It is also contraindicated in patients with elevated intracranial pressure.

Global-warming potential

Desflurane is a greenhouse gas. The twenty-year global-warming potential, GWP(20), for desflurane is 3714,{{cite journal | vauthors = Ryan SM, Nielsen CJ | title = Global Warming Potential of Inhaled Anesthetics: Application to Clinical Use | journal = Anesthesia & Analgesia | volume = 111 | issue = 1 | pages = 92–98 | publisher = International Anesthesia Research Society | location = San Francisco, CA | date = July 2010 | url = http://www.anesthesia-analgesia.org/content/111/1/92.long | doi = 10.1213/ane.0b013e3181e058d7| pmid = 20519425 | s2cid = 20737354 | access-date =9 September 2011| doi-access = free }} meaning that one tonne of desflurane emitted is equivalent to 3714 tonnes of carbon dioxide in the atmosphere, much higher than sevoflurane or isoflurane. In addition to global warming potentials, drug potency and fresh gas flow rates must be considered for meaningful comparisons between anesthetic gases. When a steady state hourly amount of anesthetic necessary for 1 minimum alveolar concentration (MAC) at 2 liters per minute (LPM) for Sevoflurane, and 1 LPM for Desflurane and Isoflurane is weighted by the GWP, the clinically relevant quantities of each anesthetic can then be compared. On a per-MAC-hour basis, the total life cycle GHG impact of desflurane is more than 20 times higher than Isoflurane and Sevoflurane (1 minimal alveolar concentration-hour).{{cite journal |vauthors=Sherman J, Le C, Lamers V, Eckelman M |title=Life Cycle Greenhouse Gas Emissions of Anesthetic Drugs |journal=Anesthesia and Analgesia|volume=114 |issue=5 |pages=1086–1090 |date=May 2012|doi=10.1213/ANE.0b013e31824f6940|pmid=22492186 |s2cid=207134715 |doi-access=free }} One paper finds anesthesia gases used globally contribute the equivalent of 1 million cars to global warming.{{cite journal |vauthors=Sulbaek Andersen MP, Sander SP, Nielsen OJ, Wagner DS, Sanford Jr TJ, Wallington TJ |title=Inhalation anaesthetics and climate change |journal=British Journal of Anaesthesia|volume=105 |issue=6 |pages=760–766 |date=July 2010|doi= 10.1093/bja/aeq259 |pmid=20935004 |doi-access=free }} This estimate is commonly cited as a reason to neglect pollution prevention by anesthesiologists. However, this is problematic. This estimate is extrapolated from only one U.S. institution's anesthetic practices, and this institution uses virtually no Desflurane. Researchers neglected to include nitrous oxide in their calculations, and reported an erroneous average of 17 kg CO2e per anesthetic. However, institutions that utilize some Desflurane and account for nitrous oxide have reported an average of 175–220 kg CO2e per anesthetic. Sulbaek-Anderson's group therefore likely underestimated the total worldwide contribution of inhaled anesthetics, and yet still advocates for inhaled anesthetic emissions prevention.{{cite conference | vauthors = Sherman JD, Schonberger RB, Eckelman M |title=Estimate of Carbon Dioxide Equivalents of Inhaled Anesthetics in the United States | id = Abstrat A3196| conference = Proceedings of the American Society of Anesthesiologists Annual Meeting | date = October 2014 | location = New Orleans, LA |url= http://www.asaabstracts.com/strands/asaabstracts/printAbstract.htm;jsessionid=491932CB9B03D78ECF6AA62FAAA0C61A?index=0&type=search&absnum=0&year=2005|website=American Society of Anesthesiologists|publisher=American Society of Anesthesiologists|access-date=3 June 2015}}{{Dead link|date=June 2021}}

In March 2023, Scotland became the first country to ban its use due to its environmental impact.{{cite web |title=Scotland first to ban environmentally harmful anaesthetic |url=https://www.bbc.co.uk/news/health-64347191 |website=BBC News |access-date=3 March 2023 |date=3 March 2023 |archive-date=3 March 2023 |archive-url=https://web.archive.org/web/20230303065848/https://www.bbc.com/news/health-64347191 |url-status=live}}