OVERVIEW

CASE REPORT

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NO	MOLECULAR FORMULA	STRUCTURE
Desflurane	57041-67-5	C3-H2-F6-O

ANNOTATED BIBLIOGRAPHY

References updated: 01 January 2018

• Zimmerman HJ. Anesthetic agents. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999: pp. 457-82.

  (Expert review of hepatotoxicity of anesthetic agents published in 1999; mentions that the newer halogenated anesthetics appear to be safer than halothane but that hints of liver injury from desflurane and sevoflurane have appeared).
• Kenna JG. Mechanism, pathology, and clinical presentation of hepatoxicity of anesthetic agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013: pp 403-22.

  (Review of liver injury from anesthetic agents mentions that a few cases of postoperative liver injury have occurred in patients exposed to desflurane).
• Patel PM, Patel HH, Roth DM. General anesthetics and therapeutic gases. In, Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill, 2011, pp. 527-64.

  (Textbook of pharmacology and therapeutics)
• Weiskopf RB, Eger EI 2nd, Ionescu P, Yasuda N, Cahalan MK, Freire B, Peterson N, et al. Desflurane does not produce hepatic or renal injury in human volunteers. Anesth Analg 1992; 74: 570-4. [PubMed: 1554124]

  (Prospective study of 13 young patients given ~7 hours of desflurane anesthesia, with no abnormalities in ALT and AST found during postoperative period).
• Kharasch ED, Thummel KE. Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology 1993; 79: 795-807. [PubMed: 8214760]

  (Human microsomes used to assess metabolism of sevoflurane: CYP 2E1 was major if not sole enzyme catalyzing defluorination of sevoflurane and others).
• Zaleski L, Abello D, Gold MI. Desflurane versus isoflurane in patients with chronic hepatic and renal disease. Anesth Analg 1993; 76: 353-6. [PubMed: 8424515]

  (Prospective study of 20 patients with renal and 20 with hepatic disease given desflurane or isoflurane found no worsening of ALT, AST, Alk P, bilirubin or creatinine).
• Katz J, Magee J, Baker B, Eger EI 2nd. Hepatic necrosis associated with herpesvirus after anesthesia with desflurane and nitrous oxide. Anesth Analg 1994; 78: 1173-6. [PubMed: 8198278]

  (76 year old woman developed fever on 6 days and abdominal pain and diarrhea 11 days after desflurance anesthesia [AST rising to 8000 U/L without jaundice] and death on day 14, autopsy showing massive hepatic necrosis due to herpes hepatitis, rather than anesthetic induced liver injury).
• Martin JL, Plevak DJ, Flannery KD, Charlton M, Poerucha JJ, Humphreys CE, Derfus G, Pohl L. Hepatotoxicity after desflurane anesthesia. Anesthesiology 1995; 83: 1125-9. [PubMed: 7486167]

  (65 year old woman devleloped fever, rash and arthralgias 12 days after desflurane anesthesia [bilirubin 20.3 rising to 30 mg/dL, ALT 1886 U/L, Alk P 202 U/L], referred for liver transplant but recovered spontaneously; had anti-TFA-modified liver microsomal proteins).
• Njoku D, Laster MJ, Gong DH, Eger EI 2nd, Reed GF, Martin JL. Biotransformation of halothane, enflurane, isoflurane, and desflurane to trifluoroacetylated liver proteins: association between protein acylation and hepatic injury. Anesth Analg 1997; 84: 173-8. [PubMed: 8989020]

  (Rats exposed to anesthetics had TFA labeled proteins in hepatocytes: halothane>>enflurane>>isoflurane, but not with desflurane; sera from cases of halothane hepatitis reacted with microsomes from halothane treated rats, but to a lesser extent with desflurane-, enflurane- and isoflurane treated rats).
• Berghaus TM, Baron A, Geier A, Lamerz R, Paumgartner G. Hepatotoxicity following desflurane anesthesia. Hepatology 1999; 29: 613-4. [PubMed: 10026031]

  (37 year old woman developed hepatitis 12 days after desflurane anesthesia [bilirubin 29.4 mg/dL, ALT 1776 U/L, Alk P 185 U/L] with evidence of liver failure, but ultimate recovery; had previous history of probable isoflurane hepatitis; anti-TFA present transiently).
• Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl 2004; 10: 1018-23. [PubMed: 15390328]

  (

  Among ~50,000 liver transplants done in the US between 1990 and 2002, 137 [0.2%] were done for idiosyncratic drug induced acute liver failure, of which 3 were attributed to halothane and 1 to isoflurane, none to other anesthetics).
• Tung D, Yoshida EM, Wang CS, Steinbrecher UP. Severe desflurane hepatotoxicity after colon surgery in an elderly patient. Can J Anaesth 2005; 52: 133-6. [PubMed: 15684251]

  (81 year old woman developed severe hepatocellular injury 6 days after desflurane anesthesia [bilirubin 6.9 rising to 12.5 mg/dL, ALT 2188 U/L, Alk P 149 U/L], with ultimate full recovery. Case 1).
• Björnsson E, Jerlstad P, Bergqvist A, Olsson R. Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden. Scand J Gastroenterol 2005; 40: 1095-101. [PubMed: 16165719]

  (36 years of reporting to Swedish registry identified 103 cases of acute liver failure due to drugs, of which 16 were attributed to halothane [ranking #1] but none to other anesthetics).
• Björnsson E, Olsson R. Suspected drug-induced liver fatalities reported to the WHO database. Dig Liver Dis 2006; 38: 33-8. [PubMed: 16054882]

  (

  In WHO database of fatal adverse drug reactions from 1968-2003, there were 4690 reports of fatalities due to drug induced liver injury: halothane ranked fifth in frequency as a cause but most cases were reported before 1991).
• Anderson JS, Rose NR, Martin JL, Eger EI, Njoku DB. Desflurane hepatitis associated with hapten and autoantigen-specific IgG4 antibodies. Anesth Analg 2007; 104: 1452-3, table of contents. (22 year old woman developed fever, jaundice and pruritus 17 to 21 days after desflurane anesthesia [bilirubin 6.2 mg/dL, ALT 347 U/L, Alk P 376 U/L] with rapid recovery; had serum antibodies to TFA and CYP 2E1). [PMC free article: PMC3650136] [PubMed: 17513640]
• Côté G, Bouchard S. Hepatotoxicity after desflurane anesthesia in a 15 month old child with Mobius syndrome after previous exposure to isoflurane. Anesthesiology 2007; 107: 843-5. [PubMed: 18073559]

  (15 month old boy developed ALT of 6,180 U/L with INR of 2.7, on postoperative day 3, after desflurane anesthesia [having two previous exposures to isoflurane], with rapid recovery; bilirubin not mentioned and patient also received acetaminophen).
• Her C. Acetaminophen-induced, not desflurane-induced, hepatotoxicity. Anesthesiology 2008; 109: 570-1. [PubMed: 18719456]

  (Letter in response to Côté and Bouchard [2007] suggesting that the liver injury was due to acetaminophen rather than desflurane using Rumack-Matthew nomogram and in view of the high ALT levels).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States.Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease collected in the US between 2003 and 2008, two cases were attributed to desflurane and one to sevoflurane; details not given).
• Chin MW, Njoku DB, MacQuillan G, Cheng WS, Kontorinis N. Desflurane-induced acute liver failure. Med J Aust 2008; 189: 293-4. [PubMed: 18759731]

  (53 year old woman developed ALT elevation to 943 U/L after initial surgery and desflurane exposure and acute liver failure after the second surgery and exposure [bilirubin not given, ALT 11,600 U/L, INR 3.7, anti-TFA positive], autopsy showing massive necrosis).
• Arslan M, Kurtipek O, Dogan AT, Unal Y, Kizil Y, Nurlu N, Kamaci S, et al. Comparison of effects of anaesthesia with desflurane and enflurane on liver function. Singapore Med J 2009; 50: 73-7. [PubMed: 19224088]

  (Prospective study of 40 patients receiving either desflurane or enflurane anesthesia for ALT, AST and glutathione-S-transferase [GST] levels showing elevations in GST but not ALT or AST at 1 hour, 1 and 7 days in enflurane group).
• D.

  evarbhavi H, Dierkhising R, Kremers WK, Sandeep MS, Karanth D, Adarsh CK. Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality. Am J Gastroenterol 2010; 105: 2396-404. PubMed Citation (313 cases of drug induced liver injury were seen over a 12 year period at a large hospital in Bangalore, India: none were attributed to anesthetic agents].
• Toprak HI, Şahin T, Aslan S, Karahan K, Şanli M, Ersoy MÖ. Effects of desflurane and isoflurane on hepatic and renal functions and coagulation profile during donor hepatectomy. Transplant Proc 2012; 44: 1635-9. [PubMed: 22841233]

  (Serial liver tests after right lobe, living donor hepatectomy showed marked elevations [up to 200 times ULN] in ALT and AST by the end of surgery through day 7, resolving by day 30, and increases in INR [1.1 to 1.5] from the end of surgery to day 5, elevations being greater among 40 donors given isoflurane than 40 given desflurane).
• Iorio ML, Cheerharan M, Kaufman SS, Reece-Stremtan S, Boyajian M. Acute Liver Failure Following Cleft Palate Repair: A Case of Therapeutic Acetaminophen Toxicity. Cleft Palate Craniofac J 2013; 50: 747-50. [PubMed: 22937760]

  (8 month old boy developed lethargy and seizures 3 days after cleft palate repair under desflurance anesthesia and while receiving acetaminophen for pain [bilirubin 3.1 mg/dL, ALT 12,885 U/L], resolving rapidly after NAC therapy).
• Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology 2013; 144: 1419-25. (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, but none were attributed to anesthetic agents). [PubMed: 23419359]
• Safari S, Motavaf M, Seyed Siamdoust SA, Alavian SM. Hepatotoxicity of halogenated inhalational anesthetics. Iran Red Crescent Med J 2014; 16: e20153. [PMC free article: PMC4270648] [PubMed: 25593732]

  (Review of hepatotoxicity of the volatile halogenated anesthetics).
• Batistaki C, Michalopoulos G, Matsota P, Nomikos T, Kalimeris K, Riga M, Nakou M, Kostopanagiotou G. CYP2E1 immunoglobulin G4 subclass antibodies after desflurane anesthesia. World J Hepatol 2014; 6: 340-6. [PMC free article: PMC4033291] [PubMed: 24868327]

  (Testing of 39 patients for liver biochemical tests and for IgG4 antibody to CYP2E1 before and 4 days after anethesia with desflurane showed no de novo production or rise in titers of the anti-CYP antibody and no evidence of liver injury).
• Lin J, Moore D, Hockey B, Di Lernia R, Gorelik A, Liew D, Nicoll A. Drug-induced hepatotoxicity: incidence of abnormal liver function tests consistent with volatile anaesthetic hepatitis in trauma patients. Liver Int 2014; 34: 576-82. [PubMed: 23944929]

  (Retrospective analysis of records from 1556 patients admitted to a trauma unit during 2008 identified 47 cases of possible volatile anesthetic related liver injury, including 12 who developed ALT levels above 200 U/L of whom 11 had fever and 6 eosinophilia, but none were jaundiced or developed acute liver failure).
• Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America. An analysis of published reports. Ann Hepatol 2014; 13: 231-9. (Systematic review of literature of drug induced liver injury in Latin American countries published from 1996 to 2012 identified 176 cases of which 5 [3%] were attributed to halothane and caused acute liver failure, while. [PubMed: 24552865]

  no other volatile anesthetic was listed).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 2 were attributed to isoflurane, 1 to sevoflurane, but none to halothane, enflurane or desflurane).