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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.
It is on the World Health Organization's List of Essential Medicines.
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.
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".
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.
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."
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.
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.
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 Wallen. The rights for sevoflurane worldwide were held by AbbVie. It is 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, however this is significantly lower than isoflurane or desflurane.
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. (2025). 9780702028588 ISBN 9780702028588 Compound A may be correlated with renal damage.
Further reading
Categories: Drugs Developed By Abbvie, Ethers, Drugs Developed By Gsk Plc, Gabaa Receptor Positive Allosteric Modulators, General Anesthetics, Glycine Receptor Agonists, Greenhouse Gases, Nicotinic Antagonists, Nmda Receptor Antagonists, 5-ht3 Antagonists, Fluranes, Organofluorides, Trifluoromethyl Compounds, Products Introduced In 1990, World Health Organization Essential Medicines, Veterinary Drugs
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