Unexpected Alterations in Fentanyl Pharmacokinetics in Children Undergoing Cardiac Surgery: Age Related or Disease Related?

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Abstract
We assessed the pharmacokinetics of fentanyl in 19 infants and children undergoing cardiac surgery for correction of tetralogy of Fallot [8], A-V-canal [4] and transposition of the great arteries [7]. Distribution T1/2 (10.2 .+-. 2.4 min) and total body clearance (13.3 .+-. 6.5 mg/kg/min) were similar to adult values. An elimination t1/2 (102 .+-. 85 min) shorter than in adults is readily explained by the significantly smaller distribution volume of the drug (1,203 .+-. 777 ml/kg). Good correlation was found between distribution volume (Vss) and elimination t1/2 (r = 0.86, p < 0.01) and between Vss and age of patients with tetralogy of Fallot (r = 0.85, p < 0.01). However, older children with Fallot''s had higher values of PO2 due to a milder condition (r = 0.89, p < 0.01); consequently PO2 correlated positively with Vss (r = 0.76, p = 0.05). Fentanyl total body clearance (TBC) tends to decrease with age in these patients (r = 0.66, p = 0.05) similar to noncardiac children. Our studies suggest that the alterations in the distribution volume of fentanyl in these children may largely depend upon the severity of the hemodynamic disturbance whereas TBC of the drug may depend on their age.

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