Toxic carbamazepine concentrations following cardiothoracic surgery and myocardial infarction

Carbamazepine is being used more frequently in the U.S. as an initial agent of choice to treat generalized tonic-clonic, mixed, and partial seizures with complex symptomatology. Carbamazepine is extensively metabolized in the liver; however, there is little information available on its pharmacokinetics in patients following surgery or myocardial infarction, or in those with liver disease. We report a case of a patient who attained toxic carbamazepine serum concentrations (ranging from 18.2 to 21.5 micrograms/mL) two days after cardiothoracic surgery and an intraoperative myocardial infarction, and experienced lethargy, diplopia, dysarthria, diaphoresis, and horizontal and downgaze nystagmus. These alterations in serum carbamazepine concentration normalized ten days after surgery. They may have been due to a combination of changes in protein binding and decreased elimination due to altered intrinsic hepatic clearance. With carbamazepine achieving a more prominent place in anticonvulsant therapy, the influence of various procedures and disease processes on the pharmacokinetics and pharmacodynamics of carbamazepine, as well as the clinical consequences of such changes, need further investigation.