Pediatric Fentanyl Dosing Based on Pharmacokinetics during Cardiac Surgery

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Abstract
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−1·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 after 30 min were 2–3-fold higher than reported with the same regimen in adults. The calculated values for t1/2α (12 · 9 min) (mean · SD), t1/2β (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 (1385 · 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 μg·ml−1 was achieved.

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