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Sevoflurane
Clinical data
Trade namesSojourn, Ultane, Sevorane, others
AHFS/ Drugs.com Consumer Drug Information
Pregnancy
category
  • AU: B2
Routes of
administration
Inhaled
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances) [1]
  • CA: ℞-only
  • UK: POM (Prescription only)
  • EU: Rx-only
Pharmacokinetic data
MetabolismLiver by CYP2E1
Metabolites Hexafluoroisopropanol
Elimination half-life15–23 hours
ExcretionKidney
Identifiers
  • 1,1,1,3,3,3-Hexafluoro-2-(fluoromethoxy)propane
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard ( EPA)
ECHA InfoCard 100.171.146 Edit this at Wikidata
Chemical and physical data
FormulaC4H3F7O
Molar mass200.056 g·mol−1
3D model ( JSmol)
Density1.53 g/cm3
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
  • Key:DFEYYRMXOJXZRJ-UHFFFAOYSA-N checkY
 ☒NcheckY  (what is this?)   (verify)

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 desflurane, it is the volatile anesthetic with the fastest onset. [2] 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. [3] [4] [5]

It is on the World Health Organization's List of Essential Medicines. [6]

Medical uses

It is one of the most commonly used volatile anesthetic agents, particularly for outpatient anesthesia, [7] 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.

Physiological effects

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 patients 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. [8] [9]

Adverse effects

Sevoflurane has an excellent safety record, [7] 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. [7] 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]

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." [10]

Additionally, there has been some investigation into potential correlation of sevoflurane use and renal damage (nephrotoxicity). [14] 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. [15]

Pharmacology

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]

History

Sevoflurane was discovered by Ross Terrell [26] and independently by 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. 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.

Global-warming potential

Sevoflurane is a greenhouse gas. The twenty-year global-warming potential, GWP(20), for sevoflurane is 349. [27]

Degradation

Sevoflurane will degrade into what is most commonly referred to as compound A (fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether) when in contact with CO2 absorbents, and this degradation tends to enhance with decreased fresh gas flow rates, increased temperatures, and increased sevoflurane concentration. [28] Compound A is what some believe is in correlation with renal damage. [29]

References

  1. ^ 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 Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^ 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.
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  5. ^ 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.
  6. ^ 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.
  7. ^ a b c "Drug Record: Sevoflurane". Livertox: Clinical and Research Information on Drug-Induced Liver Injury. 2 July 2014. PMID  31643176. Retrieved 15 August 2014.
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  10. ^ a b "Anesthetic May Affect Tau Spread in the Brain to Promote Alzheimer's Disease Pathology". Neuroscience News. 2021-05-16. Retrieved 2021-05-17.
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  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.
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  15. ^ Sondekoppam RV, Narsingani KH, Schimmel TA, McConnell BM, Buro K, Özelsel TJ (November 2020). "The impact of sevoflurane anesthesia on postoperative renal function: a systematic review and meta-analysis of randomized-controlled trials". Canadian Journal of Anaesthesia. 67 (11): 1595–1623. doi: 10.1007/s12630-020-01791-5. PMID  32812189.
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Further reading