Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of

general anesthesia General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...

. Like

halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful i ...

enflurane Enflurane (2-chloro-1,1,2-trifluoroethyl difluoromethyl ether) is a halogenated ether. Developed by Ross Terrell in 1963, it was first used clinically in 1966. It was increasingly used for inhalational anesthesia during the 1970s and 1980s but ...

, and

isoflurane Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia rather than isoflurane, due to airway irritation w ...

, it is a racemic mixture of (''R'') and (''S'') optical isomers ( enantiomers). Together with

sevoflurane Sevoflurane, sold under the brand name Sevorane, among others, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflura ...

, it is gradually replacing

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 An inhalational anesthetic is a chemical compound possessing general anesthetic properties that can be delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vapori ...

drugs used for

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). It may cause

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

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 vaporizes very readily, it is a liquid at room temperature. Anaesthetic machines are fitted with a specialized

anaesthetic vaporiser An anesthetic vaporizer (American English) or anaesthetic vaporiser (British English) is a device generally attached to an anesthetic machine which delivers a given concentration of a volatile anesthetic agent. It works by controlling the vap ...

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

and to a lesser extent

, has been shown to react with the

carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...

absorbent in anesthesia circuits to produce detectable levels of

carbon monoxide Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...

through degradation of the anesthetic agent. The absorbent Baralyme, when dried, is most culpable for the production of carbon monoxide from desflurane degradation, although it is also seen with

soda lime Soda lime is a mixture of NaOH and CaO chemicals, used in granular form in closed breathing environments, such as general anaesthesia, submarines, rebreathers and recompression chambers, to remove carbon dioxide from breathing gases to prevent ...

absorbent as well. Dry conditions in the carbon dioxide absorbent are conducive to this phenomenon, such as those resulting from high fresh gas flows.

Pharmacology

the exact mechanism of the action of general anaesthetics has not been delineated. Desflurane is known to act as a

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

of the GABA_A and glycine receptors, and as a

negative allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds t ...

of the

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

, as well as affecting other

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

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, , S. 175.

Physical properties

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.

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 iwth 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 Global warming potential (GWP) is the heat absorbed by any greenhouse gas in the atmosphere, as a multiple of the heat that would be absorbed by the same mass of carbon dioxide (). GWP is 1 for . For other gases it depends on the gas and the time ...

, GWP(20), for desflurane is 3714, meaning that one tonne of desflurane emitted is equivalent to 3714 tonnes of

in the atmosphere, much higher than

. In addition to

global warming potential Global warming potential (GWP) is the heat absorbed by any greenhouse gas in the atmosphere, as a multiple of the heat that would be absorbed by the same mass of carbon dioxide (). GWP is 1 for . For other gases it depends on the gas and the time ...

s, 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). One paper finds anesthesia gases used globally contribute the equivalent of 1 million cars to

global warming In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to E ...

. 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.

References

External links

* {{Portal bar , Medicine General anesthetics Ethers Organofluorides GABAA receptor positive allosteric modulators Glycine receptor agonists Nicotinic antagonists Fluranes Trifluoromethyl compounds Difluoromethoxy compounds