par Gepts, Elisabeth;Heytens, Luc;Camu, Frédéric 
Référence Anesthesia and analgesia, 65, 11, page (1155-1160)
Publication Publié, 1986
Référence Anesthesia and analgesia, 65, 11, page (1155-1160)
Publication Publié, 1986
Article révisé par les pairs
| Résumé : | Alfentanil was administered as a 30 μg/kg single intravenous injection to 5 healthy women scheduled for elective cesarean section (group A). In 5 pregnant women normal vaginal delivery was supported by epidural analgesia with a 30 μg/kg loading dose followed by a 30 μg/kg-1/hr-1 infusion of alfentanil (group B). Five healthy nonpregnant women scheduled for minor general surgery received 120 μg/kg alfentanil intravenously as a bolus before surgical incision (group C). In groups A and B plasma alfentanil concentrations, alfentanil plasma protein binding, and α1-acid glycoprotein (α1-AGP) concentrations were measured in maternal and umbilical arterial or venous blood samples at delivery. Multiple arterial sampling in groups A and C for measurement of alfentanil plasma concentration decay analysis indicated three-compartmental characteristics in most patients. In the pregnant population terminal half-life (t( 1/2 β), volume of distribution at steady state (Vd(ss)), and total plasma clearance (Cl(p)) amounted to 103 ± 67 min, 541 ± 155 ml/kg and 6.48 ± 0.85 ml/kg-1/min-1, respectively (mean ± SD), and did not differ significantly in nonpregnant patients. In groups A and B the fetal-maternal ratios indicated a concentration gradient for the total plasma alfentanil content (ratio of total alfentanil concentrations in umbilical venous and maternal blood (U(v)/M), 0.31 ± 0.08 and 0.28 ± 0.06 (mean ± SD) in groups A and B respectively) with a larger protein binding capacity in maternal plasma (group A, 85 ± 3%; group B, 90 ± 1%) (mean ± SD). The concentration of α1-AGP, the most important binding protein for alfentanil, was significantly lower in umbilical venous blood (22 ± 7 mg/100 ml) (mean ± SD) than in the maternal samples (group A, 42 ± 5 mg/100 ml; group B, 55 ± 13 mg/100 ml) (mean ± SD). A positive correlation was observed between the plasma alfentanil concentrations of total alfentanil and free alfentanil in the mothers and neonates, as well as between the α1-AGP concentration and the bound to free alfentanil fraction (f(b)/f(u)). Thus the intravenous pharmacokinetics of a bolus dose of alfentanil are not significantly altered in late pregnancy. Free alfentanil easily crossed the placental barrier. Because of decreased fetal α1-AGP levels, a larger free alfentanil fraction existed in neonates. |
