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

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 micrograms/kg, and after CPB, alfentanil, 80 micrograms/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 less than 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 less than 0.001). Despite intravenous administration of atropine, arterial blood pressure and heart rate decreased significantly after alfentanil was given.

Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pigs: Part II.

The pharmacokinetics of alfentanil before and after cardiopulmonary bypass (CPB) were investigated in six pigs undergoing mitral valve replacement. Before bypass, alfentanil, 100 micrograms/kg, was infused in 10 minutes and after bypass, alfentanil, 40 micrograms/kg, was infused in 10 minutes. Low inspiratory concentrations of halothane were given concomitantly. Arterial blood was obtained before and after CPB for determination of plasma alfentanil concentrations by gas chromatography. Bi-exponential functions were fitted to the plasma concentration-time data using weighted least-squares nonlinear regression analysis. The steady-state volume of distribution (Vss; 258 +/- 70 mL/kg), elimination clearance (Cle; 10.7 +/- 3.0 mL/kg/min), and distribution clearance (Cld; 6.8 +/- 3.3 mL/kg/min) before CPB were smaller than the Vss (1,107 +/- 373 mL/kg; P less than 0.01), Cle (20.0 +/- 3.0 mL/kg/min; P less than 0.002), and Cld (23.0 +/- 6.7 mL/kg/min; P less than 0.02) after CPB. The distribution half-life (t1/2 lambda 1; 2.8 +/- 0.8 minutes) was longer and the elimination half-life (t1/2 lambda 2; 36 +/- 8 minutes) was shorter before CPB than the t1/2 lambda 1 (1.7 +/- 0.2 minutes; P less than 0.05) and t1/2 lambda 2 (68 +/- 20 minutes; P less than 0.02) after CPB.

Alfentanil in infants and children with congenital heart defects.

The use of an alfentanil infusion as a supplement to a nitrous oxide-halothane anesthetic and the pharmacokinetics of alfentanil were evaluated in infants and children undergoing surgery for correction of congenital heart defects. Eleven patients, six infants and five children, were studied. Anesthesia was induced with nitrous oxide-halothane and pancuronium, 0.15 mg/kg. After intubation, anesthesia was maintained with nitrous oxide-oxygen and halothane to a maximum inspired concentration of 0.6%. After administration of atropine, 20 micrograms/kg, alfentanil, 20 micrograms/kg, was given, followed by a continuous infusion of 1 microgram/kg/min, which was stopped after closure of the sternum. Supplemental boluses of alfentanil, 5 micrograms/kg, were given when, during surgery, blood pressure and/or heart rate increased more than 20% above control values. At the end of surgery, after antagonism of residual neuromuscular blockade, the patients were extubated. Arterial blood samples were collected at regular intervals during surgery and for six hours thereafter for determination of alfentanil plasma concentrations by gas chromatography. Pharmacokinetic data were calculated using the method of residuals and noncompartmental moment analysis. Although atropine was administered, heart rate decreased significantly (2.5% to 15%) in all infants after administration of alfentanil. In the older children, blood pressure decreased 10% to 35%. In the period before bypass, three infants and four children needed supplemental boluses of alfentanil. During and after bypass, anesthesia was adequate. All patients could be extubed within 34 minutes of stopping the alfentanil infusion. Naloxone was not required in any patient, and postoperative respiratory depression did not occur. In the infants and children, total plasma clearance was 8.2 +/- 2.2 mL/kg/min and 6.3 +/- 0.8 mL/kg/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)