Pharmacokinetics of ketamine during hypothermic cardiopulmonary bypass in cardiac patients

Abstract

Cardiopulmonary bypass (CPB) makes prediction of any drug concentration diffcult because both hypothermia and hemodilution can alter the pharmacokinetics of the drug. Eleven patients undergoing cardiac surgery under CPB were anesthetized with continuous infusion of ketamine combined with intermittent administration of droperidol and fentanyl. The infusion rate of ketamine was 2 mg·kg⁻¹·hr⁻¹ following a bolus administration of 1.5 mg·kg⁻¹ for the induction of anesthesia. Blood concentrations of ketamine and its main metabolite, norketamine, were measured at 0, 30, and 60 min after the start of and the end of CPB, and 0, 1, 2, and 24 h after the cessation of ketamine infusion. Hypothermia increased blood ketamine levels during CPB, but the norketamine levels did not change. Although acute hemodilution would decrease blood ketamine levels, their levels were already significantly increased at 30 min after CPB. Hypothermic factors have a more kinetically important role during CPB than hemodilution. Increases in blood norketamine levels following rewarming indicate that hypothermia could impair ketamine metabolism in the liver. Further increase in the plasma concentration of ketamine until 30 min after the end of CPB might be due to blood transfusion containing ketamine from the CPB reservoir.