Sevoflurane

Overview

Sevoflurane, sold under the brand name Sevorane, among others, and informally known as sevo, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset. While its offset may be faster than agents other than desflurane in a few circumstances, its offset is more often similar to that of the much older agent isoflurane. 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.[1–4] WP

It is on the World Health Organization's List of Essential Medicines.[5] WP

Uses, dosage and effects

Medical uses

It is one of the most commonly used volatile anesthetic agents, particularly for outpatient anesthesia, across all ages, but particularly in pediatric anesthesia, 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.[6] WP

Physiological effects

Sevoflurane is a potent vasodilator. As such, it induces a dose dependent reduction in blood pressure and cardiac output. Though it is a bronchodilator, ketamine is preferred over it as an anaesthetic for asthmatic patients. However, in patients with pre-existing lung pathology, sevoflurane 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.[7][8] WP

Risks and side effects

Adverse effects

Sevoflurane has an excellent safety record, but is under review for potential hepatotoxicity, and may accelerate Alzheimer's. There were rare reports involving adults with symptoms similar to halothane hepatotoxicity. Sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.[6][9] WP

Sevoflurane is an inhaled anesthetic that is often used to induce and maintain anesthesia in children for surgery. 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. It is not clear if this can be prevented.[10] WP

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".[11] WP

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.[12] WP

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."[9] WP

Additionally, there has been some investigation into potential correlation of sevoflurane use and renal damage (nephrotoxicity). However, this should be subject to further investigation, as a recent study shows no correlation between sevoflurane use and renal damage as compared to other control anesthetic agents. There is also evidence that renal damage may be caused by compound A, a product of the degradation of sevoflurane; however, while compound A has been shown to mediate nephrotoxicity in animals (particularly in rats), it has not been shown to cause clinically relevant kidney injury in human subjects.[7][13–16] WP

In addition to other reported effects, studies have found that sevoflurane anaesthesia may reduce urine output and sodium excretion while increasing plasma renin concentrations compared with propofol anaesthesia. To further investigate the underlying mechanism, one study examined the effects of sevoflurane on renal function in relation to renal sympathetic nerve activity. The findings indicated that sevoflurane promotes renal sodium and water retention in paediatric patients. To clarify the role of renal sympathetic input, the researchers subsequently used a sheep model with renal denervation and demonstrated that denervation attenuated the reduction in renal excretory function observed during sevoflurane anaesthesia.[17][18] WP

Pharmacology

Pharmacology

The exact mechanism of the action of general anaesthetics has not been delineated. Sevoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors. However, it also acts as an NMDA receptor antagonist, potentiates glycine receptor currents, and inhibits nAChR and 5-HT₃ receptor currents.[19–28] WP

History

History

Sevoflurane was discovered by Ross Terrell alongside Louise Speers in the early 1960s researching at Airco Industrial Gases. Sevoflurane was concurrently synthesized by Richard Wallin. The rights for sevoflurane worldwide were held by AbbVie. It is available as a generic drug.[29] WP

Chemistry

Formula

C4H3F7O PC

CAS number

28523-86-6 PC

Molar mass (g/mol)

200.05 PC

IUPAC name (computed by PubChem)

1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane PC

SMILES

C(OC(C(F)(F)F)C(F)(F)F)F PC

InChIKey

DFEYYRMXOJXZRJ-UHFFFAOYSA-N PC

PubChem CID

5206

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Sakai EM, Connolly LA, Klauck JA. Inhalation anesthesiology and volatile liquid anesthetics: focus on isoflurane, desflurane, and sevoflurane. Pharmacotherapy. December 2005. doi:10.1592/phco.2005.25.12.1773 · PMID 16305297
2. Journal / agency Maheshwari K, Ahuja S, Mascha EJ, Cummings KC, Chahar P, Elsharkawy H, Kurz A, Turan A, Sessler DI. Effect of Sevoflurane Versus Isoflurane on Emergence Time and Postanesthesia Care Unit Length of Stay: An Alternating Intervention Trial. Anesthesia and Analgesia. February 2020. doi:10.1213/ANE.0000000000004093 · PMID 30882520
3. Journal / agency Sloan MH, Conard PF, Karsunky PK, Gross JB. Sevoflurane versus isoflurane: induction and recovery characteristics with single-breath inhaled inductions of anesthesia. Anesthesia and Analgesia. March 1996. doi:10.1213/00000539-199603000-00018 · PMID 8623956
4. Journal / agency Smith I, Ding Y, White PF. Comparison of induction, maintenance, and recovery characteristics of sevoflurane-N2O and propofol-sevoflurane-N2O with propofol-isoflurane-N2O anesthesia. Anesthesia and Analgesia. February 1992. doi:10.1213/00000539-199202000-00015 · PMID 1731547
5. Other The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
6. Journal / agency Drug Record: Sevoflurane. Livertox: Clinical and Research Information on Drug-Induced Liver Injury. 2 July 2014. PMID 31643176
7. Journal / agency Edgington TL, Muco E, Maani CV. StatPearls. 2024. PMID 30521202
8. Journal / agency Green WB. The ventilatory effects of sevoflurane. Anesthesia and Analgesia. December 1995. doi:10.1097/00000539-199512001-00004 · PMID 7486144
9. Other Anesthetic May Affect Tau Spread in the Brain to Promote Alzheimer's Disease Pathology. 16 May 2021
10. Journal / agency Costi D, Cyna AM, Ahmed S, Stephens K, Strickland P, Ellwood J, Larsson JN, Chooi C, Burgoyne LL, Middleton P. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. The Cochrane Database of Systematic Reviews. September 2014. doi:10.1002/14651858.CD007084.pub2 · PMID 25212274 · PMC10898224
11. Journal / agency Vlisides P, Xie Z. Neurotoxicity of general anesthetics: an update. Current Pharmaceutical Design. 2012. doi:10.2174/138161212803832344 · PMID 22762477
12. Journal / agency Sun L. Early childhood general anaesthesia exposure and neurocognitive development. British Journal of Anaesthesia. December 2010. doi:10.1093/bja/aeq302 · PMID 21148656 · PMC3000523
13. Journal / agency Sondekoppam RV, Narsingani KH, Schimmel TA, McConnell BM, Buro K, Özelsel TJ. The impact of sevoflurane anesthesia on postoperative renal function: a systematic review and meta-analysis of randomized-controlled trials. Canadian Journal of Anaesthesia. November 2020. doi:10.1007/s12630-020-01791-5 · PMID 32812189
14. Journal / agency Eger EI, Koblin DD, Bowland T, Ionescu P, Laster MJ, Fang Z, Gong D, Sonner J, Weiskopf RB. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesthesia and Analgesia. January 1997. doi:10.1213/00000539-199701000-00029 · PMID 8989018
15. Journal / agency Martin, Kandel, Laster. Studies of the mechanism of nephrotoxicity of compound A in rats. J Anesth. 1997
16. Other Forman SA, Ishizawa Y. Miller's Anesthesia. 2020
17. Journal / agency Franzén S, Semenas E, Taavo M, Mårtensson J, Larsson A, Frithiof R. Renal function during sevoflurane or total intravenous propofol anaesthesia: a single-centre parallel randomised controlled study. British Journal of Anaesthesia. May 2022. doi:10.1016/j.bja.2022.02.030 · PMID 35279277
18. Journal / agency Taavo M, Rundgren M, Frykholm P, Larsson A, Franzén S, Vargmar K, Valarcher JF, DiBona GF, Frithiof R. Role of Renal Sympathetic Nerve Activity in Volatile Anesthesia's Effect on Renal Excretory Function. Function. 2021-10-14. doi:10.1093/function/zqab042 · PMID 35330795 · PMC8788708
19. Other Perkins B. How does anesthesia work?. 7 February 2005
20. Journal / agency Jenkins A, Franks NP, Lieb WR. Effects of temperature and volatile anesthetics on GABA(A) receptors. Anesthesiology. February 1999. doi:10.1097/00000542-199902000-00024 · PMID 9952156
21. Journal / agency Wu J, Harata N, Akaike N. Potentiation by sevoflurane of the gamma-aminobutyric acid-induced chloride current in acutely dissociated CA1 pyramidal neurones from rat hippocampus. British Journal of Pharmacology. November 1996. doi:10.1111/j.1476-5381.1996.tb15772.x · PMID 8922750 · PMC1915958
22. Journal / agency Krasowski MD, Harrison NL. 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. February 2000. doi:10.1038/sj.bjp.0703087 · PMID 10683198 · PMC1571881
23. Other Schüttler J, Schwilden H. Modern Anesthetics. 8 January 2008
24. Journal / agency Brosnan RJ, Thiesen R. Increased NMDA receptor inhibition at an increased Sevoflurane MAC. BMC Anesthesiology. June 2012. doi:10.1186/1471-2253-12-9 · PMID 22672766 · PMC3439310
25. Other Van Dort CJ. Regulation of Arousal by Adenosine A(1) and A(2A) Receptors in the Prefrontal Cortex of C57BL/6J Mouse. 2008
26. Other Schüttler J, Schwilden H. Modern Anesthetics. 8 January 2008
27. Journal / agency Suzuki T, Koyama H, Sugimoto M, Uchida I, Mashimo T. The diverse actions of volatile and gaseous anesthetics on human-cloned 5-hydroxytryptamine3 receptors expressed in Xenopus oocytes. Anesthesiology. March 2002. doi:10.1097/00000542-200203000-00028 · PMID 11873047
28. Journal / agency Hang LH, Shao DH, Wang H, Yang JP. Involvement of 5-hydroxytryptamine type 3 receptors in sevoflurane-induced hypnotic and analgesic effects in mice. Pharmacological Reports. 2010. doi:10.1016/s1734-1140(10)70319-4 · PMID 20885002
29. Journal / agency Burns WB, Eger EI. Ross C. Terrell, PhD, an anesthetic pioneer. Anesthesia and Analgesia. August 2011. doi:10.1213/ane.0b013e3182222b8a · PMID 21642612

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.