To the Editor: It has been well established that traditional inhalational anaesthetic agents can cause mild and sometimes fulminant liver failure.1 However, while newer inhalational agents are a theoretical cause of hepatotoxicity, such cases have rarely been reported.2,3

We describe desflurane-induced acute liver failure in a 53-year-old woman with achalasia, hypertension, type 2 diabetes mellitus and hyperlipidaemia. She underwent a Heller myotomy for treatment of the achalasia in late 2004. During anaesthesia, desflurane was administered (1.2 minimum alveolar concentration [MAC]) via a Datex–Ohmeda Aestiva/5 anaesthesia delivery system (GE Healthcare, Sydney, NSW). After the operation, her serum alanine aminotransferase (ALT) concentration peaked at 943 U/L (reference range, < 35 U/L). This was attributed to antibiotic toxicity. As the initial myotomy was inadequate, the surgery was repeated 10 days later with desflurane (0.9 MAC) anaesthesia. The patient developed acute liver failure 96 hours after surgery (serum ALT level, 11 600 U/L; pH, 7.06; international normalised ratio, 3.7) and died despite supportive management. A postmortem examination confirmed massive hepatic necrosis and significantly elevated trifluoroacetyl chloride-specific IgG4 antibodies (optical density, 0.585; reference range, < 0.233) — consistent with an inhalational agent being the cause of the necrosis.

There are few similar cases of desflurane-induced acute liver failure in the literature to date2,3 and none, to our knowledge, in Australia. Fulminant hepatic necrosis induced by halothane, the original offending agent, occurs in about one in 35 000 adults. This is thought to be immune-mediated and appears to be directly correlated with the metabolism of the anaesthetic, catalysed by cytochrome P450 2E1, to trifluoroacetylated hepatic proteins. The altered protein is seen as “non-self”, generating an immune response that, on re-exposure, leads to inflammation and cellular death.4

Desflurane is metabolised to inorganic fluoride and trifluoroacetyl chloride. However, due to a lower blood : gas partition coefficient and its resistance to degradation (as a result of replacement of chlorine by fluorine at the α-carbon position), desflurane is metabolised by hepatic enzymes to a lesser extent than halothane, enflurane and isoflurane.4 Thus, the degree of hepatic metabolism appears to be related to the potential for hepatic injury, as seen clinically.

Evidence for immune-mediated, allergic sensitisation continues to emerge. Identification of IgG4 antibodies, the rarest and most IgE-like immunoglobulins, strongly suggests an allergic component in the pathophysiology of this disease.5

Although hepatotoxicity is a rare complication of the newer inhaled volatile agents, it may have devastating consequences. Anaesthetic agents should be considered in the differential diagnosis of hepatotoxicity, especially in the context of extreme elevation of serum transaminases, suggesting the presence of massive hepatic necrosis. In this case, postoperative ALT elevation was attributed to antibiotic — rather than desflurane — toxicity, with disastrous results following re-exposure, a scenario that might have been prevented if recognised earlier.

A full incident report was made at the tertiary hospital involved, and the death was reported to (and examined by) the coroner. The main recommendation made from the case was that inhalational agents should be avoided in the setting of hepatitis.