Desflurane

Clinical data
ATC code	N01AB07 (WHO)
Pharmacokinetic data
Metabolism	Not metabolized
Elimination half-life	Elimination dependent on minute ventilation
Identifiers
IUPAC name 2-(difluoromethoxy)-1,1,1,2-tetrafluoro-ethane
CAS Number	57041-67-5 Y
PubChem CID	42113
IUPHAR/BPS	7156
DrugBank	DB01189 Y
ChemSpider	38403 Y
UNII	CRS35BZ94Q
KEGG	D00546 Y
ChEBI	CHEBI:4445 Y
ChEMBL	ChEMBL1200733 N
ECHA InfoCard	100.214.382
Chemical and physical data
Formula	C3H2F6O
Molar mass	168.038 g/mol
3D model (JSmol)	Interactive image
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 Y Key:DPYMFVXJLLWWEU-UHFFFAOYSA-N Y
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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^[1]). 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.^[2]

Pharmacology[edit]

Desflurane is known to act as a positive allosteric modulator of the GABA_A and glycine receptors,^[3][4][5] and as a negative allosteric modulator of the nicotinic acetylcholine receptor,^[6][7] as well as affecting other ligand-gated ion channels.^[8][9]

Stereochemistry[edit]

Desflurane medications are a racemate of two enantiomeres.^[10]

Enantiomeres of desflurane
(R)-Enantiomer	(S)-Enantiomer

Physical properties[edit]

Global-warming potential[edit]

Desflurane is a greenhouse gas. The twenty-year global-warming potential, GWP(20), for desflurane is 3714,^[11] 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).^[12] One paper finds anesthesia gases used globally contribute the equivalent of 1 million cars to global warming.^[13] 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.^[14]

References[edit]

Further reading[edit]

• 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.