Pediatric fentanyl dosing based on pharmacokinetics during cardiac surgery

The pharmacokinetics of fentanyl (F) were studied in 10 children, age 5 months-4.5 yr (mean 19 months) undergoing cardiac surgery with cardiopulmonary bypass (CPBP). They suffered from transposition of the great arteries (6), tetralogy of Fallot (2), and atrio-ventricular (A-V) canal (2). Induction of anesthesia included a bolus of 50 μg/kg^-1.min^-1 F followed by a continuous F infusion of either 0.15 μg/kg^-1.min^-1 (4 patients) or 0.3 μg/kg^-61.min^-1 (6 patients). The F infusion was discontinued when cardiopulmonary bypass was started, 81-141 min (mean 112 min) along with deep hypothermia. Blood was collected throughout surgery from an indwelling radial arterial catheter and plasma concentration of F was assayed by GLC. F plasma concentrations afte 30 min were 2-3-fold higher than reported with the same regimen in adults. The calculated values for t(1/2α) (12 ± 9 min) (mean ± SD), t(1/2α) (141 ± 98 min) and total body clearance (12.8 ± 7.3 ml.min^-1/kg^-1) were similar to adult values. The significantly lower steady-state volume of distribution observed in children with intracardiac shunts (1.385 ± 875 ml.kg^-1) compared to reported values for adults (3200-6000 ml.kg^-1) explains the higher F plasma concentrations achieved in these children. Cardiopulmonary bypass produced a mean 70% (range, 56-89%) decrease in plasma F, significantly higher than would be expected from hemodilution alone. Studies of F disposition in the CPBP demonstrated that F is bound to the pump. Our data suggest that children with intracardiac shunts undergoing surgery under F anesthesia require an F bolus 30 μg/kg^-1 combined with a 0.3 μg/kg^-1.min^-1 continuous infusion throughout the operation. This regimen has been shown to be effective in an additional 9 children (6 months-9 yr. mean 4.4 yr; tetralogy of Fallot, 5; transposition of great arteries, 2; A-V canal, 2) in whom a steady-state F concentration of 22.7 ± 5.25 ng/ml^-1 was achieved.