Milrinone pharmacokinetics in critically ill children

Introduction: We investigated the pharmacokinetic characteristics of loading and continuous infusion therapy with railrinone in critically ill children, a group in which pharmacokinetic data are limited. Method: Fourteen children (10 after cardiac surgery, 4 with presumed septic shock, age: 0.75 to 166 months) were enrolled and received a loading dose followed by a continuous infusion of milrinone. Four to 9 timed blood samples were collected from each patient: prior to milrinone, at the end of the loading dose (Cl), -24 hours later (C2), prior to (C3), and after stopping the infusion. Milrinone concentration of extracted serum samples was measured by HPLC. The milrinone half-life (ti/z), steady state clearance (CLss), and volume of distribution (Vd) were calculated assuming Istorder elimination with an open 1-compartment model. Results: The loading dose of milrinone (48.5 ±1.9 meg/kg) resulted in Cl of 185 ± 60 ng/ml and continuous infusion (0.5 mcg/kg/min) was associated with C2 of 83.4 ± 29.1 ng/ml. At discontinuation of the drug (in 5.3 ±2.7 days) C3 was 61.4 ±18 ng/ml (C2 v C3, p-ns). CLss was 8.2 ±2.7 ml/kg/min, Vd was 0.66 ±0.38 Meg, and tm was 58 ±38 minutes. One patient developed multi-organ system failure (MOSF) and received an infusion of 0.25 mcg/kg/min: C3 was 241 ng/ml, milrinone concentration was >200 ng/ml 2 hours after stopping the infusion, CLss was 1.0 ml/kg/min and \\n was markedly prolonged (> 8 hours). Excluding the patient with MOSF, age was not correlated with any kinetic parameter. However, C2 increased with increasing serum creatinine and bilirubin (p<0.05) and Vd increased with increasing bilirubin (p<0.05). Conclusions: Milrinone pharmacokinetics in this group of critically ill children are similar to those in a small group of pédiatrie cardiac surgery patients [1]. A loading dose of 50 meg/kg followed by continuous infusion of 0.5 mcg/kg/min yielded drug concentrations initially in the range associated with effective therapy in adults (>100 ng/ml) [2]. However, the milrinone concentration declined to <100 ng/ A Huring the. infusion, suggesting the need to study increased infusion rates in children Milrinone clearance was substantially impaired in a child with MOSF. Until further kinetic data can be developed, milrinone should be used with great care, or avoided entirely, in children with MOSF.