Chemistry:Desflurane
Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether), under the brand name Suprane, is a highly fluorinated methyl ethyl ether used for induction and maintenance of general anesthesia.[1] Desflurane was developed in the 1980s and approved by the FDA in 1992 as a faster acting and clearing inhalant anesthetic compared to previously used inhalant anesthetics.[2] Like halothane, enflurane, and isoflurane, it is a racemic mixture of (R) and (S) optical isomers (enantiomers). It has the most rapid onset and offset of the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood. It is lipophobic and hydrophobic, and therefore does not easily dissolve in blood.[3]
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[4]). 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.[5] Desflurane has a high vapor pressure and a low boiling point, requiring a specific anesthetic vaporizer.[1] Anaesthetic machines are fitted with a specialized anaesthetic vaporizer unit that heats liquid desflurane at a constant temperature and pressure.[6] This enables the agent to be available at a constant vapor pressure and negating the effects of fluctuating ambient temperatures.
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 CO
2 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.[7]
Medical uses
Desflurane is a volatile inhalational anesthetic primarily used for the maintenance of general anesthesia in adults and for maintenance in pediatric patients after induction with other agents.[1] Desflurane is administered alongside other anesthetics like midazolam and propofol, analgesics, as well as air and oxygen for balanced anesthesia.[8] Unlike intravenous anesthetics, inhalation anesthetics allow for better and more rapid control over the concentration, therefore more control over the depth of anesthesia. In addition, elimination is more rapid, resulting in shorter spans of respiratory depression.[9] Desflurane is favored for its very rapid onset and offset of action, enabling swift induction and particularly fast recovery, which is advantageous for outpatient and day-case surgeries, and in populations where rapid emergence is critical, such as the elderly and obese patients. Desflurane has a low blood solubility because it is hydrophobic and lipophobic, which is why it has a fast onset and elimination[1] Additionally, its use has been explored in scenarios like cardiac surgery for potential myocardial protection and in cases of severe seizures in epileptic patients, but primary indications remain tied to its reliable profile for maintaining anesthesia with rapid, predictable recovery.[10][11]
Adverse effects
Most common side effect of inhalant anesthetics is postoperative nausea and vomiting (PONV).[8] Desflurane is generally not recommended for inhalation induction, especially in children, due to its pungency and risk of airway irritation, especially in patients with asthma, and laryngospasm.[1] Carbon monoxide toxicity can occur with desflurane as it is a large producer of carbon monoxide.[8] Hepatotoxicity is very rare with few single case reports of severe acute liver injury.[12] Desflurane can cause increased intracranial pressure.[6] In pediatric patients, Desflurane is linked to increased rate of emergence delirium post operatively.[6] Desflurane decreases blood pressure, but at high concentrations can increase blood pressure and cause tachychardia.[6] As of September 2025, Desflurane has been linked to rare cases of bradycardia, vocal cord deterioration, and disseminated intravascular coagulation.[13]
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.[6]
Pharmacology
As of 2005[update] the exact mechanism of the action of general anaesthetics has not been delineated.[14] Inhalant anesthetics work on the central and peripheral nervous systems by blocking excitatory ion channels and enhancing the activity of inhibitory ion channels, and reducing pain signals by inhibiting of spinal cord dorsal horn neurons.[1][13] Desflurane is known to act as a positive allosteric modulator of the inhibitory GABAA and an agonist of the inhibitory glycine receptors.[15][16][17] In addition, Desflurane acts as an antagonist on excitatory glutamate receptors,[18] as a negative allosteric modulator of the nicotinic acetylcholine receptor,[19][20] as well as affecting other ligand-gated ion channels.[21][22]
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.[1]
Desflurane is administered as an inhalant, and is rapidly eliminated from the lungs. It is not associated with nephrotoxicity and is resistant to defluorination.[1] It is carried by albumin in the human body and is minimally metabolized by cytochrome CYP2E1 in the liver, which produces a metabolite trifluoroacetic acid and is eliminated through the urine.[2] Only 0.02% of the metabolite is recovered from urine, the remainder eliminated through the lungs.[2]
Desflurane has a half life of 8.16 ± 3.15 minutes.[2] It has a median volume of distribution of 612 mL/kg.[2] It is produced and available as a 240ml solution.[1] There is no available data on Cmax and Tmax for desflurane as it is continuously adjusted by an anesthesiologist in real time during procedures. Instead, inhalant anesthetics are often measured by their minimal alveolar concentrations, and desflurane's MAC is 6.0% for the 31 to 65 age group and 7.25% for the 18 to 30 age group.[1] Desflurane has a blood-to-gas partition coefficient of 0.42, with a blood-to-gas coefficient of 0.47.[1]
Emergence from desflurane after an hour long procedure is on average 6 minutes.[1] Because desflurane has a short half life it is not considered to affect women who are pregnant or breastfeeding, however, there have been no well-controlled studies specifically on pregnant women.[1]
Chemistry
Stereochemistry
Desflurane medications are a racemate of two enantiomers.[23]
| Enantiomeres of desflurane | |
|---|---|
-Desfluran_Structural_Formula_V1.svg) (R)-Enantiomer |
-Desfluran_Structural_Formula_V1.svg) (S)-Enantiomer |
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 Daltons | ||
| 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
As Desflurane is a polyfluorinated ether, it is a greenhouse gas.[24] The twenty-year global-warming potential, GWP(20), for desflurane is about 3700, meaning that one tonne of desflurane emitted is equivalent to 3700 tonnes of carbon dioxide in the atmosphere, much higher than sevoflurane or isoflurane. Sevoflurane and isoflurane are replacing desflurane globally as hospitals try to minimize their carbon footprint.[25] It has been estimated that halogenated anaesthetic agents used by health systems covering 80% of global population in 2023 emitted about 2 million tonnes CO2eq, 70% stemming from desflurane.[26] England, Scotland and parts of Canada have banned desflurane use (except in exceptional circumstances) due to its environmental impact.[27][28]
However unlike nitrous oxide, which is also used as an anaesthetic and remains in the atmosphere for over a century, the atmospheric lifetime of desflurane at 14.1 years is similar to methane at 12.4 years. Some argue that GWP is not a suitable metric for such short lived climate pollutants, and that due to its negligible radiative forcing desflurane is not a significant part of greenhouse gas emissions from the healthcare sector.[29]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 "Desflurane". StatPearls. Treasure Island (FL): StatPearls Publishing. 2025. https://www.ncbi.nlm.nih.gov/books/NBK537106/. Retrieved 2025-10-06.
- ↑ 2.0 2.1 2.2 2.3 2.4 "Desflurane" (in en). https://go.drugbank.com/drugs/DB01189.
- ↑ "Carbonic anhydrase enzymes: Likely targets for inhalational anesthetics". Medical Hypotheses 123: 118–124. February 2019. doi:10.1016/j.mehy.2019.01.005. PMID 30696581.
- ↑ Varkey JK (October 2012). Cost Analysis of Desflurane and Sevoflurane: An Integrative Review and Implementation Project Introducing the Volatile Anesthetic Cost Calculator (Doctor of Nursing Practice thesis). Texas Christian University.
- ↑ "Desflurane" (in en). https://go.drugbank.com/drugs/DB01189.
- ↑ 6.0 6.1 6.2 6.3 6.4 "Desflurane". StatPearls. Treasure Island (FL): StatPearls Publishing. 2022. https://www.ncbi.nlm.nih.gov/books/NBK537106/.
- ↑ "Carbon monoxide production from degradation of desflurane, enflurane, isoflurane, halothane, and sevoflurane by soda lime and Baralyme". Anesthesia and Analgesia 80 (6): 1187–1193. June 1995. doi:10.1097/00000539-199506000-00021. PMID 7762850.
- ↑ 8.0 8.1 8.2 "Inhalational Anesthetic". StatPearls. Treasure Island (FL): StatPearls Publishing. 2025. https://www.ncbi.nlm.nih.gov/books/NBK554540/. Retrieved 2025-11-06.
- ↑ "Desflurane" (in en). PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/42113.
- ↑ "Myocardial Protection by Desflurane: From Basic Mechanisms to Clinical Applications". Journal of Cardiovascular Pharmacology 82 (3): 169–179. September 2023. doi:10.1097/FJC.0000000000001448. PMID 37405905.
- ↑ "Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane". Archives of Neurology 61 (8): 1254–1259. August 2004. doi:10.1001/archneur.61.8.1254. PMID 15313843.
- ↑ "LiverTox: An online information resource and a site for case report submission on drug-induced liver injury". Clinical Liver Disease 4 (1): 22–25. July 2014. doi:10.1002/cld.388. PMID 30992914.
- ↑ 13.0 13.1 "Desflurane Safety Revisited: A Pharmacovigilance Study Detecting Potential Safety Signals from FAERS Data" (in English). Journal of Pain Research 18: 5069–5080. 2025-09-26. doi:10.2147/JPR.S544011. PMID 41041661.
- ↑ "How does anesthesia work?". Scientific American. 7 February 2005. https://www.scientificamerican.com/article/how-does-anesthesia-work/.
- ↑ Foundations of Anesthesia: Basic Sciences for Clinical Practice. Elsevier Health Sciences. 2006. pp. 290–291. ISBN 978-0-323-03707-5. https://books.google.com/books?id=xaXu1wHmENoC&pg=PA290.
- ↑ Miller's Anesthesia. Elsevier Health Sciences. 20 October 2014. pp. 624–. ISBN 978-0-323-28011-2. https://books.google.com/books?id=L2ckBQAAQBAJ&pg=PA624.
- ↑ "The actions of sevoflurane and desflurane on the gamma-aminobutyric acid receptor type A: effects of TM2 mutations in the alpha and beta subunits". anesthesiology 99 (3): 678–684. Sep 2003. doi:10.1097/00000542-200309000-00024. PMID 12960553.
- ↑ "Molecular mechanisms of general anesthesia". Korean Journal of Anesthesiology 59 (1): 3–8. July 2010. doi:10.4097/kjae.2010.59.1.3. PMID 20651990.
- ↑ Clinical Cases in Anesthesia. Elsevier Health Sciences. 2 December 2013. pp. 101–. ISBN 978-0-323-18654-4. https://books.google.com/books?id=9VVJAgAAQBAJ&pg=PA101.
- ↑ Clinical Anesthesia (7th ed.). Lippincott Williams & Wilkins. 7 February 2013. pp. 470–. ISBN 978-1-4698-3027-8. https://books.google.com/books?id=exygUxEuxnIC&pg=PA470.
- ↑ A Practice of Anesthesia for Infants and Children: Expert Consult – Online and Print. Elsevier Health Sciences. 2013. pp. 499–. ISBN 978-1-4377-2792-0. https://books.google.com/books?id=MAXTnQStL0cC&pg=PA499.
- ↑ Essential Clinical Anesthesia Review: Keywords, Questions and Answers for the Boards. Cambridge University Press. 8 January 2015. pp. 128–. ISBN 978-1-107-68130-9. https://books.google.com/books?id=VJzWBQAAQBAJ&pg=PA128.
- ↑ 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.
- ↑ "The Environmental Impact of Inhaled Anesthetics". American Society of Anesthesiologists. https://www.asahq.org/about-asa/governance-and-committees/asa-committees/environmental-sustainability/greening-the-operating-room/inhaled-anesthetics.
- ↑ "Environmental impact of desflurane". NSW Ministry of Health. Government of New South Wales, Australia. February 2024. https://www.health.nsw.gov.au/netzero/Factsheets/environmental-impact-desflurane.pdf.
- ↑ "Greenhouse gas impact from medical emissions of halogenated anaesthetic agents: a sales-based estimate" (in English). The Lancet. Planetary Health 9 (3): e227–e235. March 2025. doi:10.1016/S2542-5196(25)00027-0. PMID 40120629.
- ↑ "Scotland first to ban environmentally harmful anaesthetic". 3 March 2023. https://www.bbc.co.uk/news/health-64347191.
- ↑ "Start here: How NWT and NL are tackling the surprising environmental impact of anesthetics" (in en). https://www.cma.ca/latest-stories/start-here-how-nwt-and-nl-are-tackling-surprising-environmental-impact-anesthetics.
- ↑ "The science of climate change and the effect of anaesthetic gas emissions". Anaesthesia 79 (3): 252–260. March 2024. doi:10.1111/anae.16189. PMID 38205585.
Further reading
- The Pharmacology of Inhaled Anesthetics. New Providence. 2003.
- Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. 2003. ISBN 978-0-443-07145-4.
- Bellgard M (2005). Evaluation der Sedierungstiefe und der Aufwachzeiten frisch operierter Patienten mit neurophysiologischem Monitoring im Rahmen der Studie: Desfluran versus Propofol zur Sedierung beatmeter Patienten [Evaluation of the depth of sedation and recovery times of newly operated patients with neurophysiological monitoring as part of the study: desflurane versus propofol for sedation of ventilated patients.] (PDF) (Ph.D. thesis) (in Deutsch). Bochum. Archived from the original (PDF) on 22 May 2011.
- Lohmann S (2006). Verträglichkeit, Nebenwirkungen und Hämodynamik der inhalativen Sedierung mit Desfluran im Rahmen der Studie: Desfluran versus Propofol zur Sedierung beatmeter Patienten [Tolerability, side effects and hemodynamics of inhaled sedation with desflurane in the context of the study: desflurane versus propofol for sedation of mechanically ventilated patients.] (PDF) (Ph.D. thesis) (in Deutsch). Bochum. Archived from the original (PDF) on 4 March 2016.)
- "Desflurane. A review of its pharmacodynamic and pharmacokinetic properties and its efficacy in general anaesthesia". Drugs 50 (4): 742–767. October 1995. doi:10.2165/00003495-199550040-00010. PMID 8536556.
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