Central nervous system toxicity associated with meperidine use in hepatic disease

Meperidine-associated central nervous system (CNS) excitatory toxicities are believed to be caused by accumulation of the active metabolite normeperidine. Normeperidine is eliminated by the kidneys and accumulates in patients with renal insufficiency, sickle cell disease, and cancer. In patients with cirrhosis, the metabolism of meperidine is decreased, leading to accumulation of the parent drug and possible CNS depressive effects similar to hepatic encephalopathy. Although the elimination of normeperidine is decreased as well in these patients, the ratio of normeperidine to meperidine is generally low, and the narcotic effects of meperidine usually predominate. This is the first reported case of CNS excitatory toxicities in a patient with alcoholic hepatitis and cirrhosis, and normal renal function. Administration of multiple doses of meperidine in patients with hepatic disease should be discouraged.