Sevoflurane

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Sevoflurane
Sevoflurane.svg
Sevoflurane-3D-balls.png
Clinical data
Trade names Ultane, others
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
  • AU:B2
Routes of
administration
Inhalation
Drug class Anesthetic
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Liver by CYP2E1
Metabolites Hexafluoroisopropanol
Elimination half-life 15–23 hours
Excretion Kidney
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 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C4H3F7O
Molar mass 200.056 g·mol−1
3D model (JSmol)
Density 1.53 g/cm3
Boiling point 58.5 °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 Yes check.svgY
  • Key:DFEYYRMXOJXZRJ-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (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. [8] 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. [9] [10] [11]

Contents

It is on the World Health Organization's List of Essential Medicines. [12]

Medical uses

It is one of the most commonly used volatile anesthetic agents, particularly for outpatient anesthesia, [13] 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. [14] [15]

Adverse effects

Sevoflurane has an excellent safety record, [13] but is under review for potential hepatotoxicity, and may accelerate Alzheimer's. [16] There were rare reports involving adults with symptoms similar to halothane hepatotoxicity. [13] Sevoflurane is the preferred agent for mask induction due to its lesser irritation to mucous membranes.

Sevoflurane is an inhaled anesthetic that is often used to induce and maintain anesthesia in children for surgery. [17] 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. [17] It is not clear if this can be prevented. [17]

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". [18]

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. [19]

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." [16]

Additionally, there has been some investigation into potential correlation of sevoflurane use and renal damage (nephrotoxicity). [20] 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. [21]

Pharmacology

The exact mechanism of the action of general anaesthetics has not been delineated. [22] Sevoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors. [23] [24] [25] [26] However, it also acts as an NMDA receptor antagonist, [27] potentiates glycine receptor currents, [26] and inhibits nAChR [28] and 5-HT3 receptor currents. [29] [30] [31]

History

Sevoflurane was discovered by Ross Terrell. [32] 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. [33]

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. [34] Compound A may be correlated with renal damage. [35]

Related Research Articles

General anaesthetics are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompass multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

<span class="mw-page-title-main">Halothane</span> General anaesthetic

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 in those who are difficult to intubate. It is given by inhalation.

<span class="mw-page-title-main">Isoflurane</span> General anaesthetic given via inhalation

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, due to airway irritation with isoflurane. Isoflurane is given via inhalation.

<span class="mw-page-title-main">General anaesthesia</span> Medically induced loss of consciousness

General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of consciousness that renders a patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an analgesic and neuromuscular blocking agent. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway. General anaesthesia is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an intensive care unit or emergency department to facilitate endotracheal intubation and mechanical ventilation in critically ill patients. Depending on the procedure, general anaesthesia may be optional or required. Regardless of whether a patient may prefer to be unconscious or not, certain pain stimuli could result in involuntary responses from the patient that may make an operation extremely difficult. Thus, for many procedures, general anaesthesia is required from a practical perspective.

<span class="mw-page-title-main">Theories of general anaesthetic action</span> How drugs induce reversible suppression of consciousness

A general anaesthetic is a drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anaesthetist/anesthesiologist to induce or maintain general anaesthesia to facilitate surgery.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Desflurane</span> Chemical compound

Desflurane (1,2,2,2-tetrafluoroethyl difluoromethyl ether) is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane, and isoflurane, it is a racemic mixture of (R) and (S) optical isomers (enantiomers). Together with sevoflurane, it is gradually replacing isoflurane for human use, except in economically undeveloped areas, where its high cost precludes its use. It has the most rapid onset and offset of the volatile anesthetic drugs used for general anesthesia due to its low solubility in blood.

<span class="mw-page-title-main">Bispectral index</span> Technology for monitoring anesthesia

Bispectral index (BIS) is one of several technologies used to monitor depth of anesthesia. BIS monitors are used to supplement Guedel's classification system for determining depth of anesthesia. Titrating anesthetic agents to a specific bispectral index during general anesthesia in adults allows the anesthetist to adjust the amount of anesthetic agent to the needs of the patient, possibly resulting in a more rapid emergence from anesthesia. Use of the BIS monitor could reduce the incidence of intraoperative awareness during anaesthesia. The exact details of the algorithm used to create the BIS index have not been disclosed by the company that developed it.

<span class="mw-page-title-main">Remifentanil</span> Synthetic opioid analgesic

Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

<span class="mw-page-title-main">Inhalational anesthetic</span> Volatile or gaseous anesthetic compound delivered by inhalation

An inhalational anesthetic is a chemical compound possessing general anesthetic properties that is delivered via inhalation. They are administered through a face mask, laryngeal mask airway or tracheal tube connected to an anesthetic vaporiser and an anesthetic delivery system. Agents of significant contemporary clinical interest include volatile anesthetic agents such as isoflurane, sevoflurane and desflurane, as well as certain anesthetic gases such as nitrous oxide and xenon.

Minimum alveolar concentration or MAC is the concentration, often expressed as a percentage by volume, of a vapour in the alveoli of the lungs that is needed to prevent movement in 50% of subjects in response to surgical (pain) stimulus. MAC is used to compare the strengths, or potency, of anaesthetic vapours. The concept of MAC was first introduced in 1965.

<span class="mw-page-title-main">Methoxyflurane</span> Chemical compound

Methoxyflurane, sold under the brand name Penthrox among others, is an inhaled medication primarily used to reduce pain following trauma. It may also be used for short episodes of pain as a result of medical procedures. Onset of pain relief is rapid and of a short duration. Use is only recommended with direct medical supervision.

Veterinary anesthesia is a specialization in the veterinary medicine field dedicated to the proper administration of anesthetic agents to non-human animals to control their consciousness during procedures. A veterinarian or a Registered Veterinary Technician administers these drugs to minimize stress, destructive behavior, and the threat of injury to both the patient and the doctor. The duration of the anesthesia process goes from the time before an animal leaves for the visit to the time after the animal reaches home after the visit, meaning it includes care from both the owner and the veterinary staff. Generally, anesthesia is used for a wider range of circumstances in animals than in people not only due to their inability to cooperate with certain diagnostic or therapeutic procedures, but also due to their species, breed, size, and corresponding anatomy. Veterinary anesthesia includes anesthesia of the major species: dogs, cats, horses, cattle, sheep, goats, and pigs, as well as all other animals requiring veterinary care such as birds, pocket pets, and wildlife.

<span class="mw-page-title-main">Flurothyl</span> Chemical compound

Flurothyl (Indoklon) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, but having the opposite effects, acting as a stimulant and convulsant. A clear and stable liquid, it has a mild ethereal odor whose vapors are non-flammable. It is excreted from the body by the lungs in an unchanged state.

Emergence delirium is a condition in which emergence from general anesthesia is accompanied by psychomotor agitation. Some see a relation to pavor nocturnus while others see a relation to the excitement stage of anesthesia.

Blood–gas partition coefficient, also known as Ostwald coefficient for blood–gas, is a term used in pharmacology to describe the solubility of inhaled general anesthetics in blood. According to Henry's law, the ratio of the concentration in blood to the concentration in gas that is in contact with that blood, when the partial pressure in both compartments is equal, is nearly constant at sufficiently low concentrations. The partition coefficient is defined as this ratio and, therefore, has no units. The concentration of the anesthetic in blood includes the portion that is undissolved in plasma and the portion that is dissolved. The more soluble the inhaled anesthetic is in blood compared to in air, the more it binds to plasma proteins in the blood and the higher the blood–gas partition coefficient.

Obstetric anesthesia or obstetric anesthesiology, also known as ob-gyn anesthesia or ob-gyn anesthesiology, is a sub-specialty of anesthesiology that provides peripartum pain relief (analgesia) for labor and anesthesia for cesarean deliveries ('C-sections').

James Edward Cottrell is the Chair Emeritus, Department of Anesthesiology at SUNY Downstate Medical Center in New York City. He serves as a member of the New York State Board of Regents and is an avid collector of contemporary fine-art.

Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, and the common anesthetic agent propofol was licensed in 1986. TIVA is currently employed in various procedures as an alternative technique of general anesthesia in order to improve post-operative recovery.

The effects of early-life exposures to anesthesia on the brain in humans are controversial. Evidence from nonhuman primate research suggests significant developmental neurotoxicity and long-term social impairment, with a dose–response relationship where repeated exposures cause a more severe impact than single ones. Research in humans has not found conclusive clinical evidence of cognitive impairment; however, systematic reviews imply the possibility of greater behavioural impairments in children exposed to anesthesia before the age of three than control subjects.

References

  1. Anvisa (31 March 2023). "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 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. "Ultane- sevoflurane liquid". DailyMed. 18 August 2022. Retrieved 29 June 2024.
  3. "Sojourn- sevoflurane liquid". DailyMed. 26 June 2024. Retrieved 29 June 2024.
  4. "SevoFlo EPAR". European Medicines Agency. 14 August 2007. Retrieved 29 June 2024.
  5. "SevoFlo PI". Union Register of medicinal products. 13 December 2002. Retrieved 29 June 2024.
  6. "Sevohale (previously known as Sevocalm) EPAR". European Medicines Agency. 29 July 2016. Retrieved 29 June 2024.
  7. "Sevohale PI". Union Register of medicinal products. 24 June 2016. Retrieved 29 June 2024.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 1 2 3 "Drug Record: Sevoflurane". Livertox: Clinical and Research Information on Drug-Induced Liver Injury. 2 July 2014. PMID   31643176 . Retrieved 15 August 2014.
  14. Edgington TL, Muco E, Maani CV (2024). "Sevoflurane". StatPearls. StatPearls Publishing. PMID   30521202.
  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. 1 2 "Anesthetic May Affect Tau Spread in the Brain to Promote Alzheimer's Disease Pathology". Neuroscience News. 16 May 2021. Retrieved 17 May 2021.
  17. 1 2 3 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. 2014 (9): CD007084. doi:10.1002/14651858.CD007084.pub2. PMC   10898224 . PMID   25212274.
  18. Vlisides P, Xie Z (2012). "Neurotoxicity of general anesthetics: an update". Current Pharmaceutical Design. 18 (38): 6232–6240. doi:10.2174/138161212803832344. PMID   22762477.
  19. 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.
  20. Edgington TL, Muco E, Naani CV (2023). "Sevoflurane". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   30521202 . Retrieved 5 November 2023.
  21. 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.
  22. Perkins B (7 February 2005). "How does anesthesia work?". Scientific American . Retrieved 30 June 2016.
  23. 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.
  24. 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.
  25. 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.
  26. 1 2 Schüttler J, Schwilden H (8 January 2008). Modern Anesthetics. Springer Science & Business Media. pp. 32–. ISBN   978-3-540-74806-9.
  27. 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.
  28. Van Dort CJ (2008). Regulation of Arousal by Adenosine A(1) and A(2A) Receptors in the Prefrontal Cortex of C57BL/6J Mouse. University of Michigan. pp. 120–. ISBN   978-0-549-99431-2.[ permanent dead link ]
  29. Schüttler J, Schwilden H (8 January 2008). Modern Anesthetics. Springer Science & Business Media. pp. 74–. ISBN   978-3-540-74806-9.
  30. 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.
  31. 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. doi:10.1016/s1734-1140(10)70319-4. PMID   20885002.
  32. 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.
  33. Ryan SM, Nielsen CJ (July 2010). "Global warming potential of inhaled anesthetics: application to clinical use". Anesthesia and Analgesia. 111 (1). International Anesthesia Research Society: 92–98. doi: 10.1213/ane.0b013e3181e058d7 . PMID   20519425.
  34. Pawson P, Forsyth S (2008). "Anesthetic agents". Small Animal Clinical Pharmacology. pp. 83–112. doi:10.1016/B978-070202858-8.50007-5. ISBN   978-0-7020-2858-8.
  35. Eger EI, Koblin DD, Bowland T, Ionescu P, Laster MJ, Fang Z, et al. (January 1997). "Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers". Anesthesia and Analgesia. 84 (1): 160–168. doi:10.1213/00000539-199701000-00029. PMID   8989018.

Further reading