Biotransformation of Halothane, Enflurane, Isoflurane, and Desflurane to Trifluoroacetylated Liver Proteins

Njoku, Dolores B.; Laster, Michael J.; Gong, Diane; Eger, Edmond I.; Reed, George F.; Martin, Jackie L.

doi:10.1213/00000539-199701000-00031

Cited by 178 publications

(72 citation statements)

References 19 publications

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“…2,5 The etiology of severe halothane-induced hepatitis is thought to be immunologically mediated. 2,5,6 Halothane is metabolized by the cytochrome P-450 system resulting in the formation of several reactive intermediates, principally trifluoroacetyl chloride, 1,8 which is able to bind to amino groups of proteins. This results in the formation of TFA hepatic proteins.…”

Section: Discussionmentioning

confidence: 99%

“…This results in the formation of TFA hepatic proteins. 1,2,8 These TFA hepatic proteins seem to be immunogenic. In sensitized patients these TFA hepatic proteins cause specific antibody and/or T-cell responses leading to hepatic injury of various severities.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 All patients anesthetized with these agents have the potential to form these altered liver proteins that can act as haptens. At re-exposure to any of these halogenated volatile anesthetics, an immune-mediated toxicity may rarely cause volatile anesthetic-induced hepatitis, leading to hepatic injury which may occasionally be fatal.…”

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confidence: 99%

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Case report: Fatal hepatic failure after aortic valve replacement and sevoflurane exposure

Lehmann

Neher

Kiessling

et al. 2007

Can J Anesth/J Can Anesth

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Purpose: To report a case of lethal hepatotoxicity possibly caused by sevoflurane. Clinical features:A 76-yr-old woman with a history of four previous minor surgical procedures developed acute liver failure after general anesthesia with sevoflurane, sufentanil and propofol for aortic valve replacement. After an uneventful procedure the patient was extubated 4.5 hr after surgery. On the second postoperative day, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased. On the third postoperative day liver failure occurred, ALT peaked at 10504 U·L -1 and AST at 15516 U·L -1 , and coagulopathy with an international normalized ratio of 4.6 developed. Liver transplantation was considered but rejected as a therapeutic option. The patient died three days after the operation in multiple organ failure triggered by hepatic failure. Other possible causes for liver failure were excluded. Conclusions:Sevoflurane hepatitis as a cause for liver failure may be implicated in this patient undergoing valve surgery. Unlike other halogenated anesthetic drugs, sevoflurane is not metabolized to hepatotoxic trifluroacetyl proteins. However, compound A may react with proteins and may be transformed into antigenic material. We suggest that all halogenated anesthetics may be implicated with acute liver injury.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Case report: Fatal hepatic failure after aortic valve replacement and sevoflurane exposure

Lehmann

Neher

Kiessling

et al. 2007

Can J Anesth/J Can Anesth

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show abstract

“…Modification of liver proteins through trifluoroacylation by metabolites of volatile anesthetics is thought to produce immunogenic adducts eliciting a specific immune response resulting in hepatic damage 3,4 and possible sensitization to future exposure. Desflurane is a newer anesthetic agent that is not generally considered to be associated with liver injury.…”

Section: éLéments Cliniques : Une Lésion Hépatique Aiguë Sévère S'estmentioning

confidence: 99%

“…2 The mechanism responsible for the hepatic damage is thought to be immunologic. Oxidation of halothane by the cytochrome P-450 (CYP) system results in the formation of several reactive intermediates, principally trifluoroacetyl chloride 3,4 that can bind covalently to amino groups of proteins. This leads to the formation of trifluoroacetylated (TFA) liver microsomal proteins that are thought to be immunogenic, and elicit specific antibody and/or T-cell responses.…”

Section: éLéments Cliniques : Une Lésion Hépatique Aiguë Sévère S'estmentioning

confidence: 99%

Severe desflurane hepatotoxicity after colon surgery in an elderly patient

Tung

Yoshida

Wang

et al. 2005

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : To report a case of desflurane hepatotoxicity.C Cl li in ni ic ca al l f fe ea at tu ur re es s: : An 81-yr-old woman with a remote history of abdominal surgery developed severe acute liver injury after general anesthesia with desflurane for resection of colonic cancer. Serum alanine aminotransferase and aspartate aminotransferase peaked at postoperative day six (2188 and 425 U·L -1 respectively), with the development of coagulopathy with an international normalized ratio of 2.29 on postoperative day eight, progressive jaundice with a peak serum total bilirubin of 214 µmol·L -1 on postoperative day 12 and hepatic encephalopathy on postoperative day ten. Other causes for liver disease were excluded. Treatment with corticosteroids was started. The liver biochemistry normalized completely by postoperative day 30 and the patient was discharged from hospital on postoperative day 21.C Co on nc cl lu us si io on ns s: : To our knowledge, this represents only the third report of desflurane hepatotoxicity and the first with reversible fulminant liver failure. Our experience suggests that all fluorinated anesthetics may cause acute hepatic damage. Objectif : Présenter un cas d'hépatotoxicité au desflurane.

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Desfluran [MAK Value Documentation in German language, 2012]

2012

The MAK‐Collection for Occupational Health and Safety

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Veröffentlicht in der Reihe Gesundheitsschädliche Arbeitsstoffe , 52. Lieferung, Ausgabe 2012 Der Artikel enthält folgende Kapitel: Allgemeiner Wirkungscharakter Wirkungsmechanismus Neuronale Mechanismen Kovalente Bindung zwischen Trifluoressigsäure und Leberproteinen Toxikokinetik und Metabolismus Aufnahme, Verteilung, Ausscheidung Metabolismus Erfahrungen beim Menschen Einmalige Exposition Wiederholte Exposition Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Tierexperimentelle Befunde und In‐vitro‐Untersuchungen Akute Toxizität Subakute, subchronische und chronische Toxizität Wirkung auf Haut und Schleimhäute Allergene Wirkung Reproduktionstoxizität Genotoxizität Kanzerogenität Bewertung

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Biotransformation of Halothane, Enflurane, Isoflurane, and Desflurane to Trifluoroacetylated Liver Proteins

Cited by 178 publications

References 19 publications

Case report: Fatal hepatic failure after aortic valve replacement and sevoflurane exposure

Case report: Fatal hepatic failure after aortic valve replacement and sevoflurane exposure

Severe desflurane hepatotoxicity after colon surgery in an elderly patient

Desfluran [MAK Value Documentation in German language, 2012]

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