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 General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...

. 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.

Medical uses

It is one of the most commonly used volatile anesthetic agents, particularly for outpatient anesthesia,Livertox: Clinical and Research Information on Drug-Induced Liver Injury (2014) "Drug Record: Sevoflurane", U.S. National Library of Medicine, 2 July 2014 update, se

accessed 15 August 2014. across all ages, as well as in veterinary medicine. Together with desflurane, sevoflurane is replacing

isoflurane Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia rather than isoflurane, due to airway irritation w ...

and

halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful i ...

in modern anesthesia practice. It is often administered in a mixture of

nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has ...

and oxygen.

Physiologic effects

Sevoflurane is a potent vasodilator, as such it induces a dose dependent reduction in blood pressure and cardiac output. It is a brondilator, 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.

Adverse Effects

Sevoflurane has an excellent safety record, but is under review for potential

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn fr ...

, and may accelerate Alzheimer's. There were rare reports involving adults with symptoms similar to

. Sevoflurane is the preferred agent for mask induction due to its lesser irritation to

mucous membrane A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It i ...

s. Sevoflurane was discovered by Ross Terrell 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 AbbVie is an American publicly traded biopharmaceutical company founded in 2013. It originated as a spin-off of Abbott Laboratories. History On October 19, 2011, Abbott Laboratories announced its plan to separate into two publicly traded compani ...

. It is now available as a generic drug. Sevoflurane is an inhaled anaesthetic that is often used to put children asleep for surgery. During the process of waking up from the medication, it has been known to cause agitation and delirium. It is not clear if this can be prevented.

Adverse effects

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 urtherinformation" 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."

Pharmacology

The exact mechanism of the action of general anaesthetics has not been delineated. Sevoflurane acts as a

positive allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...

of the GABA_A receptor in

electrophysiology Electrophysiology (from Ancient Greek, Greek , ''ēlektron'', "amber" ee the Electron#Etymology, etymology of "electron" , ''physis'', "nature, origin"; and , ''-logy, -logia'') is the branch of physiology that studies the electrical propertie ...

studies of neurons and recombinant receptors. However, it also acts as an

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

, potentiates glycine receptor currents, and inhibits nAChR and 5-HT₃ receptor currents.

Global-warming potential

Sevoflurane is a greenhouse gas. The twenty-year

global-warming potential Global warming potential (GWP) is the heat absorbed by any greenhouse gas in the atmosphere, as a multiple of the heat that would be absorbed by the same mass of carbon dioxide (). GWP is 1 for . For other gases it depends on the gas and the time ...

, GWP(20), for sevoflurane is 349.

References

External links

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

, titlestyle = background:#ccccff , list1 = {{GABAA receptor modulators {{Glycine receptor modulators {{Ionotropic glutamate receptor modulators {{Nicotinic acetylcholine receptor modulators {{Serotonin receptor modulators General anesthetics Ethers Organofluorides AbbVie brands GSK plc brands GABAA receptor positive allosteric modulators Glycine receptor agonists Nicotinic antagonists NMDA receptor antagonists 5-HT3 antagonists Fluranes Trifluoromethyl compounds Products introduced in 1990 Greenhouse gases