Volatile Anesthetics and Liver Function Tests
Sevoflurane and desflurane can cause transient elevations in liver function tests, but these are typically mild, self-limited, and clinically insignificant in most patients. 1, 2
Evidence from FDA Drug Labeling
The FDA label for sevoflurane explicitly states that transient elevations in liver function tests may occur, similar to other anesthetic agents. 1 Post-marketing reports have documented cases of mild, moderate, and severe hepatic dysfunction or hepatitis with or without jaundice, though most patients had underlying hepatic conditions or were receiving hepatotoxic medications. 1
Comparative Evidence Between Agents
Desflurane vs. Sevoflurane
Desflurane appears to cause less hepatic enzyme elevation than sevoflurane at equivalent doses. 2 In living liver donors undergoing right hepatectomy:
- AST elevations were significantly higher with sevoflurane from the day of surgery through postoperative day 3. 2
- ALT was significantly elevated on postoperative days 1 and 3 in the sevoflurane group compared to desflurane. 2
- Albumin levels were significantly lower on postoperative day 2 with sevoflurane. 2
- No patients developed hepatic failure with either agent. 2
Sevoflurane vs. Isoflurane
Isoflurane induces elevation of serum liver enzymes more frequently than sevoflurane, particularly 3-14 days after anesthesia. 3 In neurosurgical patients, AST, ALT, and GTP increased and peaked seven days after anesthesia, especially in the isoflurane group. 3
Metabolism and Mechanism
Desflurane undergoes minimal metabolism (0.02-0.2% of dose), while sevoflurane metabolism is approximately 2-5% of the dose taken up. 4 This difference in metabolic burden likely explains the differential effects on liver enzymes:
- Desflurane's major metabolites are inorganic fluoride and trifluoroacyl chloride. 4
- Sevoflurane's major metabolites are fluoride and hexafluoroisopropanol (HFIP), which is rapidly glucuronidated. 4
- Peak serum fluoride concentrations after sevoflurane occur within one hour and are usually 20-40 μM. 4
Clinical Context and Significance
In elderly patients undergoing low-flow anesthesia, both desflurane and sevoflurane minimally affect hepatic integrity. 5 Standard liver enzyme markers showed no significant changes throughout the study period, though alpha-glutathione S-transferase (a sensitive marker of hepatocyte injury) increased transiently in both groups, returning to baseline within 24 hours postoperatively. 5
After hepatectomy with inflow occlusion, sevoflurane and propofol resulted in similar patterns of liver function tests, with no significant differences in peak ALT or AST between groups. 6 This suggests that in the context of major hepatic surgery, the choice between volatile and intravenous anesthetics does not significantly impact postoperative liver enzyme elevations. 6
Important Caveats
Contraindications exist for patients with prior moderate to severe hepatic dysfunction following halogenated anesthetics. 7 The FDA label for desflurane specifically contraindicates its use in patients with a history of moderate to severe hepatic dysfunction following anesthesia with desflurane or other halogenated agents that is not otherwise explained. 7
Most reported cases of hepatic dysfunction occurred in patients with underlying hepatic conditions or concurrent hepatotoxic medications. 1 The transient nature of enzyme elevations and spontaneous resolution in most cases suggests these changes represent temporary hepatocellular stress rather than clinically significant injury. 1
Biotransformation investigations suggest sevoflurane does not result in clinically significant hepatotoxicity, though only a single case of immune-mediated desflurane hepatotoxicity has been reported. 4