Hepatotoxicity enflurane

Isoflurane, an isomer of enflurane, together with sevoflurane are the most commonly used inhalation anesthetics in humans. Isoflurane does not sensitize the myocardium to catecholamines, has muscle relaxing action so less neuromuscular blocker is required and causes less hepatotoxicity and renal toxicity than halothane. 

Enflurane is a fluorinated methyl ethyl ether and is a structural isomer of isoflurane (Figure 3.2). It was synthesised in 1963 and introduced into clinical practice in 1966 at a time when concern was growing about the hepatotoxicity of halothane. Its main advantage over halothane was its resistance to biotransformation (2.5% compared to some 20%). For that reason it was widely used as an alternative to halothane, particularly for multiple administration. 

Pauli JD, Fortune DW. Hepatotoxicity and death following two enflurane anaesthetics. Anaesthesia 1987 42(11) 1191-6. 

Enflurane reduces renal blood flow, glomerular filtration rate, and urinary output. These effects are rapidly reversed upon drug discontinuation. There is scant evidence of long-term nephrotoxicityfollowing enflurane use, and it is safe to use in patients with renal impairment provided that the depth of enflurane anesthesia and the duration of administration are not excessive. Enflurane reduces splanchnic and hepatic blood flow in proportion to reduced arterial blood pressure but does not appear to alter liver function or to be hepatotoxic. 

Halothane also can produce another form of hepatotoxicity. This is a self-limiting hepatic dysfunction characterized by elevated liver transaminase enzymes, which probably results from impaired oxygenation of the hepatocytes during exposure to this anesthetic. Isoflurane and enflurane also have been reported to produce a similar elevation of liver enzymes, although to a lesser extent than halothane. 

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