Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pediatric patients undergoing cardiac surgery: Part I

Abstract

Changes induced by cardiopulmonary bypass (CPB) may markedly affect the pharmacokinetics of drugs. Therefore, the pharmacokinetics of alfentanil before and after CPB were compared in infants and children undergoing cardiac surgery, who had been anesthetized with nitrous oxide in oxygen and low inspiratory concentrations of halothane. Six infants and six children were investigated. Before CPB, alfentanil, 200 μg/kg, and after CPB, alfentanil, 80 μg/kg, was infused in 10 minutes. Arterial blood samples were obtained before and after CPB for determination of plasma alfentanil concentrations. Bi-exponential functions were fitted to the plasma concentration-time data using weighted least-squares nonlinear regression analysis. A correction was made to account for the contribution of the first infusion to the plasma concentrations measured during and after the second infusion. Total sampling time before CPB (45 to 75 minutes) was too short to allow full characterization of the pharmacokinetics of alfentanil, but allowed estimation of the initial volume of distribution. The initial volume of distribution before CPB was smaller (68 ± 37 mL/kg in infants and 80 ± 32 mL/kg in children) than after CPB (235 ± 58 mL/kg in infants and 179 ± 99 mL/kg in children; P < 0.001). The normalized area under the plasma concentration-time curve from 0 to 45 minutes was larger before CPB (17.9 ± 2.9 mg · min/L in infants and 18.3 ± 5.4 mg · min/ L in children) than after CPB (11.1 ± 2.9 mg · min /L in infants and 12.9 ± 3.4 mg·min /L in children; P < 0.001). Despite intravenous administration of atropine, arterial blood pressure and heart rate decreased significantly after alfentanil was given.