Specific Considerations with Liver Disease - Metabolism of Anesthetics
- Induction agents
- Propofol is metabolized by the liver (HER ~ 1) to water-soluble compounds that are excreted by the kidneys. Extrahepatic metabolism of propofol also contributes to total propofol clearance.
- Barbiturates have a duration of action that is determined by redistribution and hepatic metabolism and may have prolonged effects in patients with liver disease. Hypoalbuminemia, as seen in patients with altered liver function, may reduce protein binding and increases the free active fraction of these drugs. Therefore, barbiturates must be titrated carefully in patients with liver disease.
- Ketamine is metabolized by the hepatic microsomal enzyme system to norketamine, which has approximately 30% of the activity of the parent drug. Ketamine has an HER of approximately 1.
- Etomidate is metabolized by the liver through ester hydrolysis to inactive metabolites. Similar to ketamine, etomidate has a high HER, so clearance is affected by conditions that reduce hepatic blood flow. Recovery from an initial induction dose is primarily due to rapid redistribution.
- Benzodiazepines and opioids are metabolized primarily by the liver and have significantly increased half-lives in patients with liver disease. Additionally, they have increased potency in cases of hypoalbuminemia as these drugs, which are usually protein bound, are now free in the plasma resulting in higher drug levels. This issue may confound the clinical picture of hepatic encephalopathy and should be titrated carefully.
- Neuromuscular blocking agents. Patients with liver disease often demonstrate resistance to nondepolarizing neuromuscular blockers, probably because of increased volume of distribution or increased neuromuscular receptors. However, a slower elimination time may decrease the requirement for maintenance dosing.
- Pancuronium is excreted primarily in the urine but 10% to 20% is metabolized in the liver. The 3-hydroxymetabolite has neuromuscular blocker activity. Approximately 30% of pancuronium is eliminated through hepatobiliary mechanisms, and its effect may be prolonged in patients with biliary obstruction or cirrhosis.
- Intermediate-acting neuromuscular blocking drugs, vecuronium and rocuronium, are highly dependent on hepatobiliary excretion and metabolism (both are excreted, 50% unchanged, in the bile). This translates to a decreased clearance and a prolonged effect in patients with liver disease. Vecuronium undergoes hepatic metabolism to several compounds, one of which is 3-desacetylvecuronium that 50% of vecuronium's neuromuscular blocker activity. Cisatracurium and atracurium are degraded via Hofmann elimination and are unaffected by liver disease.
- Succinylcholine and mivacurium (not available in the United States) are completely metabolized in the plasma by pseudocholinesterase. Cholinesterase production may be depressed in severe liver disease, and its duration may be prolonged in patients with hepatic dysfunction.
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