Population Pharmacokinetics and Dosing of Milrinone After Patent Ductus Arteriosus Ligation in Preterm Infants

Objectives: The postoperative course of patent ductus arteriosus ligation is often complicated by postligation cardiac syndrome, occurring in 10–45% of operated infants. Milrinone might prevent profound hemodynamic instability and improve the recovery of cardiac function in this setting. The present study aimed to describe the population pharmacokinetics of milrinone in premature neonates at risk of postligation cardiac syndrome and give dosing recommendations. Design: A prospective single group open-label pharmacokinetics study. Settings: Two tertiary care neonatal ICUs: Tallinn Children’s Hospital and Tartu University Hospital, Estonia. Patients: Ten neonates with postmenstrual age of 24.6–30.1 weeks and postnatal age of 5–27 days undergoing patent ductus arteriosus ligation and at risk of postligation cardiac syndrome, based on echocardiographic assessment of left ventricular output of less than 200 mL/kg/min 1 hour after the surgery. Interventions: Milrinone at a dose of 0.73 μg/kg/min for 3 hours followed by 0.16 μg/kg/min for 21 hours. Four blood samples from each patient for milrinone plasma concentration measurements were collected. Measurements and Main Results: Concentration-time data of milrinone were analyzed with nonlinear mixed-effects modeling software (NONMEM Version 7.3 [ICON Development Solutions, Ellicott City, MD]). Probability of target attainment simulations gave a dosing schedule that maximally attains concentration targets ...
Source: Pediatric Critical Care Medicine - Category: Pediatrics Tags: Cardiac Intensive Care Source Type: research