A prospective study of the incidence of drug‐induced liver injury by the modern volatile anaesthetics sevoflurane and desflurane

Author:

Bishop Bridget1ORCID,Hannah Nicholas1,Doyle Adam23,Amico Francesco2,Hockey Brad4,Moore David4,Sood Siddharth12,Gorelik Alexandra15,Liew Danny156,Njoku Dolores7,Nicoll Amanda1289ORCID

Affiliation:

1. Melbourne Medical School, Dentistry and Health Sciences University of Melbourne Melbourne Australia

2. Department of Gastroenterology and Hepatology Royal Melbourne Hospital Melbourne Australia

3. Department of Gastroenterology and Hepatology Royal Perth Hospital Perth Australia

4. Department of Anaesthesia and Pain Management Royal Melbourne Hospital Melbourne Australia

5. Melbourne EpiCentre, Royal Melbourne Hospital Melbourne Australia

6. Division of Clinical Epidemiology, School of Public Health and Preventative Medicine Monash University Melbourne Australia

7. Departments of Anesthesiology and Critical Care Medicine, Pediatrics, and Pathology Johns Hopkins University Baltimore Maryland

8. Department of Gastroenterology Eastern Health Melbourne Australia

9. Eastern Health Clinical School, Monash School of Medicine, Monash University Melbourne Australia

Abstract

SummaryBackgroundVolatile anaesthetics are known to cause drug‐induced liver injury, a hepatotoxic reaction characterised by antibodies to trifluoroacetylated lipid and protein adducts and cytochrome p450 2E1. The incidence of volatile anaesthetic drug‐induced liver injury from older agents has been described, but modern agents have not been prospectively studied.AimTo determine prospectively the incidence of volatile anaesthetic drug‐induced liver injury from sevoflurane and desflurane.MethodsAdult surgical patients with a predicted post‐operative stay of at least 4 days were recruited. If volatile anaesthetic was administered, liver biochemistry was performed regularly. Medications, observations and other investigations were documented. Patients with abnormal liver biochemistry were classified as likely volatile anaesthetic drug‐induced liver injury or not based on clinical assessment, Roussel Uclaf Causality Assessment Method score, and the absence of other likely pathology. Some patients were also tested for antibodies to both trifluoroacetylated lipid and protein adducts, and cytochrome p450 2E1.ResultsA total of 209 patients were recruited, of which 121 were included for analysis. Post‐operative liver biochemistry was abnormal in 62 patients (51.2%); further classified as not volatile anaesthetic drug‐induced liver injury in 47 cases (38.8%), and likely volatile anaesthetic‐drug induced liver injury in 15 cases (12.4%). Of the likely volatile anaesthetic drug‐induced liver injury patients, only one had severe disease with alanine transaminase greater than five times the upper limit of normal, while four cases had moderate disease with alanine transaminase greater than three times the upper limit of normal. Thus, the incidence of clinically significant volatile anaesthetic drug‐induced liver injury was 4.1%. No risk factors were identified.ConclusionsVolatile anaesthetic drug‐induced liver injury from modern agents seems to be as common (4.1%) as previously reported with older agents (3%), and may identify patients at risk of severe acute liver injury with subsequent re‐exposure.

Funder

Royal Melbourne Hospital

Johns Hopkins University

Publisher

Wiley

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