From WikiProjectMed
Jump to navigation Jump to search
Trade namesSojourn, Ultane, Sevorane, others
  • 1,1,1,3,3,3-Hexafluoro-2-(fluoromethoxy)propane
Clinical data
Drug classInhalational anaesthetic
Main usesBegin and maintain general anesthesia[1]
Side effectsCough, nausea, increased saliva, QT prolongation[2]
  • AU: B2
Routes of
Typical dose0.5 to 8%[2]
External links
AHFS/Drugs.comConsumer Drug Information
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances) [3]
  • UK: POM (Prescription only)
  • EU: Rx-only
MetabolismLiver by CYP2E1
Elimination half-life15–23 hours
Chemical and physical data
Molar mass200.056 g·mol−1
3D model (JSmol)
Boiling point58.5 °C (137.3 °F)
  • FC(F)(F)C(OCF)C(F)(F)F
  • InChI=1S/C4H3F7O/c5-1-12-2(3(6,7)8)4(9,10)11/h2H,1H2 checkY

Sevoflurane, sold under the brand name Sevorane, among others, is an inhalational anaesthetic used to begin and maintain general anesthesia.[1] Onset is rapid with a fast recovery.[1][4] It can be used instead of propofol to begin anesthesia.[4]

Safety is good.[1] Side effects may include cough, nausea, increased saliva, and QT prolongation.[2] It does not irritate the lungs, and therefore may be used safely in people with reactive airway disease.[1][4] Rare cases of liver problems have occurred.[1] It should not be used in people at risk of malignant hyperthermia.[2] It may be used safely when breastfeeding.[5]

Sevoflurane was first made in the 1960s by Ross Terrell and has been in use in Japan since 1990.[6] It was approved for medical use in the United States in 1995.[1] It is on the World Health Organization's List of Essential Medicines.[7] As of 2005 it was more expensive than isoflurane or desflurane in the United States.[4] In the United Kingdom a 250 ml container costs the NHS £123 as of 2023.[8]

Medical uses

It is one of the most commonly used volatile anesthetic agents, particularly for outpatient anesthesia,[9] across all ages, as well as in veterinary medicine. Together with desflurane, sevoflurane is replacing isoflurane and halothane in modern anesthesia practice. It is often administered in a mixture of nitrous oxide and oxygen.


Doses of 0.5% to 8% may be used.[2]

Side effects

Sevoflurane has an excellent safety record,[9] but is under review for potential hepatotoxicity, and may accelerate Alzheimer's.[10] There were rare reports involving adults with symptoms similar to halothane hepatotoxicity.[9] Sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.

Sevoflurane is an inhaled anaesthetic that is often used to induction and maintenance of anaesthesia in children for surgery.[11] During the process of awakening from the medication, it has been associated with a high incidence (>30%) of agitation and delirium in preschool children undergoing minor noninvasive surgery.[11] It is not clear if this can be prevented.[11]

Studies examining a current significant health concern, anesthetic-induced neurotoxicity (including with sevoflurane, and especially with children and infants) are "fraught with confounders, and many are underpowered statistically", and so are argued to need "further data... to either support or refute the potential connection".[12]

Concern regarding the safety of anaesthesia is especially acute with regard to children and infants, where preclinical evidence from relevant animal models suggest that common clinically important agents, including sevoflurane, may be neurotoxic to the developing brain, and so cause neurobehavioural abnormalities in the long term; two large-scale clinical studies (PANDA and GAS) were ongoing as of 2010, in hope of supplying "significant [further] information" on neurodevelopmental effects of general anaesthesia in infants and young children, including where sevoflurane is used.[13]


Sevoflurane is a potent vasodilator, as such it induces a dose dependent reduction in blood pressure and cardiac output. It is a bronchodilator, however, in people with pre-existing lung pathology it may precipitate coughing and laryngospasm. It reduces the ventilatory response to hypoxia and hypercapnia and impedes hypoxic pulmonary vasoconstriction. Sevoflurane vasodilatory properties also cause it to increase intracranial pressure and cerebral blood flow. However, it reduces cerebral metabolic rate. [14][15]


The exact mechanism of the action of general anaesthetics has not been delineated.[16] Sevoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors.[17][18][19][20] However, it also acts as an NMDA receptor antagonist,[21] potentiates glycine receptor currents,[20] and inhibits nAChR[22] and 5-HT3 receptor currents.[23][24][25]

While sevoflurane is only half as soluble as isoflurane in blood, the tissue blood partition coefficients of isoflurane and sevoflurane are quite similar. For example, in the muscle group: isoflurane 2.62 vs. sevoflurane 2.57. In the fat group: isoflurane 52 vs. sevoflurane 50. As a result, the longer the case, the more similar will be the emergence times for sevoflurane and isoflurane.[26][27][28]


Sevoflurane was discovered independently by Ross Terrell[29] and Bernard M Regan. A detailed report of its development and properties appeared in 1975 in a paper authored by Richard Wallin, Bernard Regan, Martha Napoli and Ivan Stern.[30] It was introduced into clinical practice initially in Japan in 1990 by Maruishi Pharmaceutical Co., Ltd. Osaka, Japan. The rights for sevoflurane worldwide were held by AbbVie. It is now available as a generic drug.

Society and culture

Global warming

Sevoflurane is a greenhouse gas. The twenty-year global-warming potential, GWP(20), for sevoflurane is 349.[31]


In 2021, researchers at Massachusetts General Hospital published in Communications Biology research that sevoflurane may accelerate existing Alzheimer's or existing tau protein to spread: "These data demonstrate anesthesia-associated tau spreading and its consequences. [...] This tau spreading could be prevented by inhibitors of tau phosphorylation or extracellular vesicle generation." According to Neuroscience News, "Their previous work showed that sevoflurane can cause a change (specifically, phosphorylation, or the addition of phosphate) to tau that leads to cognitive impairment in mice. Other researchers have also found that sevoflurane and certain other anesthetics may affect cognitive function."[32]


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Sevoflurane". LiverTox. 1 January 2018. Archived from the original on 3 December 2022. Retrieved 12 September 2023. {{cite web}}: Check date values in: |date= (help)
  2. 2.0 2.1 2.2 2.3 2.4 "Sevoflurane". BNF. Archived from the original on 13 September 2023. Retrieved 12 September 2023.
  3. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in português do Brasil). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  4. 4.0 4.1 4.2 4.3 Sakai EM, Connolly LA, Klauck JA (December 2005). "Inhalation anesthesiology and volatile liquid anesthetics: focus on isoflurane, desflurane, and sevoflurane". Pharmacotherapy. 25 (12): 1773–1788. doi:10.1592/phco.2005.25.12.1773. PMID 16305297. S2CID 40873242.
  5. "Drugs and Lactation Database (LactMed®) [Internet]". 16 November 2020. PMID 30000564. Archived from the original on 12 August 2022. Retrieved 12 September 2023. {{cite journal}}: Cite journal requires |journal= (help)
  6. Eger, Edmond (2013). The Wondrous Story of Anesthesia. Springer Science & Business Media. p. 133. ISBN 9781461484417. Archived from the original on 13 September 2023. Retrieved 12 September 2023.
  7. World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  8. "Sevoflurane Medicinal forms". BNF. Archived from the original on 13 September 2023. Retrieved 12 September 2023.
  9. 9.0 9.1 9.2 "Drug Record: Sevoflurane". Livertox: Clinical and Research Information on Drug-Induced Liver Injury. 2 July 2014. PMID 31643176. Archived from the original on 23 November 2016. Retrieved 15 August 2014.
  10. "Anesthetic May Affect Tau Spread in the Brain to Promote Alzheimer's Disease Pathology". Neuroscience News. 2021-05-16. Archived from the original on 2021-05-17. Retrieved 2021-05-17.
  11. 11.0 11.1 11.2 Costi D, Cyna AM, Ahmed S, Stephens K, Strickland P, Ellwood J, et al. (September 2014). "Effects of sevoflurane versus other general anaesthesia on emergence agitation in children". The Cochrane Database of Systematic Reviews. 9 (9): CD007084. doi:10.1002/14651858.CD007084.pub2. PMID 25212274.
  12. Vlisides P, Xie Z (2012). "Neurotoxicity of general anesthetics: an update". Current Pharmaceutical Design. 18 (38): 6232–6240. doi:10.2174/138161212803832344. PMID 22762477.
  13. Sun L (December 2010). "Early childhood general anaesthesia exposure and neurocognitive development". British Journal of Anaesthesia. 105 (Suppl 1): i61–i68. doi:10.1093/bja/aeq302. PMC 3000523. PMID 21148656.
  14. Edgington TL, Muco E, Maani CV (2022). "Sevoflurane". StatPearls. PMID 30521202. Archived from the original on 2022-07-09. Retrieved 2023-08-16.
  15. Green WB (December 1995). "The ventilatory effects of sevoflurane". Anesthesia and Analgesia. 81 (6 Suppl): S23–S26. doi:10.1097/00000539-199512001-00004. PMID 7486144.
  16. Perkins B (7 February 2005). "How does anesthesia work?". Scientific American. Archived from the original on 29 May 2016. Retrieved 30 June 2016.
  17. Jenkins A, Franks NP, Lieb WR (February 1999). "Effects of temperature and volatile anesthetics on GABA(A) receptors". Anesthesiology. 90 (2): 484–491. doi:10.1097/00000542-199902000-00024. PMID 9952156.
  18. Wu J, Harata N, Akaike N (November 1996). "Potentiation by sevoflurane of the gamma-aminobutyric acid-induced chloride current in acutely dissociated CA1 pyramidal neurones from rat hippocampus". British Journal of Pharmacology. 119 (5): 1013–1021. doi:10.1111/j.1476-5381.1996.tb15772.x. PMC 1915958. PMID 8922750.
  19. Krasowski MD, Harrison NL (February 2000). "The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations". British Journal of Pharmacology. 129 (4): 731–743. doi:10.1038/sj.bjp.0703087. PMC 1571881. PMID 10683198.
  20. 20.0 20.1 Schüttler J, Schwilden H (8 January 2008). Modern Anesthetics. Springer Science & Business Media. pp. 32–. ISBN 978-3-540-74806-9.
  21. Brosnan RJ, Thiesen R (June 2012). "Increased NMDA receptor inhibition at an increased Sevoflurane MAC". BMC Anesthesiology. 12 (1): 9. doi:10.1186/1471-2253-12-9. PMC 3439310. PMID 22672766.
  22. Van Dort CJ (2008). Regulation of Arousal by Adenosine A(1) and A(2A) Receptors in the Prefrontal Cortex of C57BL/6J Mouse. pp. 120–. ISBN 978-0-549-99431-2.{{cite book}}: CS1 maint: url-status (link)
  23. Schüttler J, Schwilden H (8 January 2008). Modern Anesthetics. Springer Science & Business Media. pp. 74–. ISBN 978-3-540-74806-9. Archived from the original on 23 August 2023. Retrieved 16 August 2023.
  24. Suzuki T, Koyama H, Sugimoto M, Uchida I, Mashimo T (March 2002). "The diverse actions of volatile and gaseous anesthetics on human-cloned 5-hydroxytryptamine3 receptors expressed in Xenopus oocytes". Anesthesiology. 96 (3): 699–704. doi:10.1097/00000542-200203000-00028. PMID 11873047. S2CID 6705116.
  25. Hang LH, Shao DH, Wang H, Yang JP (2010). "Involvement of 5-hydroxytryptamine type 3 receptors in sevoflurane-induced hypnotic and analgesic effects in mice". Pharmacological Reports. 62 (4): 621–626. CiteSeerX doi:10.1016/s1734-1140(10)70319-4. PMID 20885002. S2CID 4754446.
  26. Maheshwari K, Ahuja S, Mascha EJ, Cummings KC, Chahar P, Elsharkawy H, et al. (February 2020). "Effect of Sevoflurane Versus Isoflurane on Emergence Time and Postanesthesia Care Unit Length of Stay: An Alternating Intervention Trial". Anesthesia and Analgesia. 130 (2): 360–366. doi:10.1213/ANE.0000000000004093. PMID 30882520.
  27. Sloan MH, Conard PF, Karsunky PK, Gross JB (March 1996). "Sevoflurane versus isoflurane: induction and recovery characteristics with single-breath inhaled inductions of anesthesia". Anesthesia and Analgesia. 82 (3): 528–532. doi:10.1213/00000539-199603000-00018. PMID 8623956.
  28. Smith I, Ding Y, White PF (February 1992). "Comparison of induction, maintenance, and recovery characteristics of sevoflurane-N2O and propofol-sevoflurane-N2O with propofol-isoflurane-N2O anesthesia". Anesthesia and Analgesia. 74 (2): 253–259. doi:10.1213/00000539-199202000-00015. PMID 1731547. S2CID 12345796.
  29. Burns WB, Eger EI (August 2011). "Ross C. Terrell, PhD, an anesthetic pioneer". Anesthesia and Analgesia. 113 (2): 387–389. doi:10.1213/ane.0b013e3182222b8a. PMID 21642612. S2CID 19988772.
  30. Wallin RF, Regan BM, Napoli MD, Stern IJ (Nov–Dec 1975). "Sevoflurane: a new inhalational anesthetic agent". Anesthesia and Analgesia. 54 (6): 758–766. doi:10.1213/00000539-197511000-00021. PMID 1239214. S2CID 26832938.
  31. Ryan SM, Nielsen CJ (July 2010). "Global warming potential of inhaled anesthetics: application to clinical use". Anesthesia and Analgesia. International Anesthesia Research Society. 111 (1): 92–98. doi:10.1213/ane.0b013e3181e058d7. PMID 20519425. S2CID 20737354.
  32. "Anesthetic May Affect Tau Spread in the Brain to Promote Alzheimer's Disease Pathology". Neuroscience News. 2021-05-16. Archived from the original on 2021-05-17. Retrieved 2021-05-17.

External links