Desflurane

Desflurane

Systematic (IUPAC) name
2-(difluoromethoxy)-1,1,1,2-tetrafluoro-ethane
Pharmacokinetic data
Metabolism	Not metabolized
Biological half-life	Elimination dependent on minute ventilation
Identifiers
CAS Number	57041-67-5
ATC code	N01AB07 (WHO)
PubChem	CID 42113
IUPHAR/BPS	7156
DrugBank	DB01189
ChemSpider	38403
UNII	CRS35BZ94Q
KEGG	D00546
ChEBI	CHEBI:4445
ChEMBL	CHEMBL1200733
Chemical data
Formula	C3H2F6O
Molar mass	168.038 g/mol
SMILES FC(F)(F)C(F)OC(F)F
InChI InChI=1S/C3H2F6O/c4-1(3(7,8)9)10-2(5)6/h1-2H Key: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. It may cause tachycardia and airway irritability when administered at concentrations greater than 10 vol%. Due to this airway irritability, desflurane is infrequently used to induce anesthesia via inhalation techniques.

Though it vaporises 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.^[1]

Pharmacology

Desflurane is known to act as a positive allosteric modulator of the GABA_A and glycine receptors,^[2][3] and as a negative allosteric modulator of the nicotinic acetylcholine receptor,^[4][5] as well as affecting other ligand-gated ion channels.^[6][7]

Physical properties

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

Global-warming potential

Desflurane is a greenhouse gas. Anesthesia gases used globally contribute the equivalent of 1 million cars to global warming.^[8] The twenty-year global-warming potential, GWP(20), for desflurane is 3714,^[9] meaning that one tonne of desflurane emitted is equivalent to 3714 tonnes of carbon dioxide in the atmosphere, much higher than sevoflurane or isoflurane. Taking into account the different amounts typically used in 1 hour of anesthesia (1 minimal alveolar concentration-hour), desflurane causes equivalent potential of contributing to global warming as sevoflurane.^[10]

Research

A recent clinical study found that desflurane has lower bispectral index and greater hypnotic effect than sevoflurane during the equipotent anesthesia.^[11]

References

1. Fang; et al. (1995). "Carbon Monoxide Production from Degradation of Desflurane" (PDF). Anesthesia and Analgesia.
2. Hugh C. Hemmings; Philip M. Hopkins (2006). Foundations of Anesthesia: Basic Sciences for Clinical Practice. Elsevier Health Sciences. pp. 290–291. ISBN 0-323-03707-0.
3. Ronald D. Miller; Lars I. Eriksson; Lee A Fleisher; Jeanine P. Wiener-Kronish; Neal H Cohen; William L. Young (20 October 2014). Miller's Anesthesia. Elsevier Health Sciences. pp. 624–. ISBN 978-0-323-28011-2.
4. Allan P. Reed; Francine S. Yudkowitz (2 December 2013). Clinical Cases in Anesthesia. Elsevier Health Sciences. pp. 101–. ISBN 978-0-323-18654-4.
5. Paul Barash; Bruce F. Cullen; Robert K. Stoelting; Michael Cahalan; Christine M. Stock; Rafael Ortega (7 February 2013). Clinical Anesthesia, 7e: Print + Ebook with Multimedia. Lippincott Williams & Wilkins. pp. 470–. ISBN 978-1-4698-3027-8.
6. Charles J. Coté; Jerrold Lerman; Brian J. Anderson (2013). A Practice of Anesthesia for Infants and Children: Expert Consult - Online and Print. Elsevier Health Sciences. pp. 499–. ISBN 1-4377-2792-1.
7. Linda S. Aglio; Robert W. Lekowski; Richard D. Urman (8 January 2015). Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards. Cambridge University Press. pp. 128–. ISBN 978-1-107-68130-9.
8. Sulbaek Andersen MP, Sander SP, Nielsen OJ, Wagner DS, Sanford Jr TJ, Wallington TJ (July 2010). "Inhalation anaesthetics and climate change". British Journal of Anaesthesia 105 (6): 760–766. doi:10.1093/bja/aeq259.
9. Ryan, Susan M.; Nielsen, Claus J. (July 2010). "Global Warming Potential of Inhaled Anesthetics: Application to Clinical Use". Anesthesia & Analgesia (San Francisco, CA: International Anesthesia Research Society) 111 (1): 92–98. doi:10.1213/ane.0b013e3181e058d7. Retrieved 9 September 2011.
10. Ryan SM, Nielsen CJ (July 2010). "Global Warming Potential of Inhaled Anesthetics: Application to Clinical Use". Anesthesia and Analgesia 111 (1): 92–98. doi:10.1213/ane.0b013e3181e058d7.
11. Kim JK (Feb 2014). "Relationship of bispectral index to minimum alveolar concentration during isoflurane, sevoflurane or desflurane anaesthesia.". J Int Med Res 42 (1): 130–7. doi:10.1177/0300060513505525. PMID 24366495.

Book references and additional reading

• Eger, Eisenkraft, Weiskopf. The Pharmacology of Inhaled Anesthetics. 2003.
• Rang, Dale, Ritter, Moore. Pharmacology 5th Edition. 2003.
• Martin Bellgardt: Evaluation der Sedierungstiefe und der Aufwachzeiten frisch operierter Patienten mit neurophysiologischem Monitoring im Rahmen der Studie: Desfluran versus Propofol zur Sedierung beatmeter Patienten. Bochum, Dissertation, 2005 (pdf)
• Susanne Lohmann: Verträglichkeit, Nebenwirkungen und Hämodynamik der inhalativen Sedierung mit Desfluran im Rahmen der Studie: Desfluran versus Propofol zur Sedierung beatmeter Patienten. Bochum, Dissertation, 2006 (pdf)
• Patel SS, Goa KL. (1995) "Desflurane. A review of its pharmacodynamic and pharmacokinetic properties and its efficacy in general anaesthesia." Drugs Oct;50(4):742-67. PMID 8536556.