Pharmacokinetic Study of Milrinone in Babies With Persistent Pulmonary Hypertension of the Newborn

Persistent pulmonary hypertension of the newborn (PPHN) is a condition in which the
pulmonary vasculature fails to relax after birth resulting in severe hypoxemia. This
condition has a high rate of mortality and morbidity. The current standard of care is
treatment with inhaled nitric oxide (iNO). However, for many babies this treatment does not
provide sufficient improvement in oxygenation.

In this study, subjects already receiving nitric oxide will be randomized to one of two
dosing regimens of milrinone. They will receive milrinone IV for 24 hours and will be
monitored for 24 hours afterwards. During this time, milrinone assays will be performed by
blood sampling. Echocardiograms will also be performed to explore the pharmacodynamics of
milrinone. Safety monitoring will be performed.

Inclusion Criteria:

- Gestational age > 34 weeks

- Post-natal age < 10 days

- Hypoxemia defined by: Oxygenation Index (OI) >15 (Mean Airway Pressure x Fraction of
Inspired Oxygen x 100 /PaO2) as drawn from two post-ductal arterial blood gas samples
(in-dwelling arterial catheter) taken at least 15 minutes apart. OR mechanically
ventilated and with >75% FiO2 for >6 hours while on iNO

- Absence of congenital heart disease based on a two-dimensional echocardiogram and/or
clinical assessment

- An in-dwelling arterial catheter to facilitate painless sampling

- Currently on iNO or plan to start iNO before enrollment

Exclusion Criteria:

- Lethal non-cardiac congenital anomalies including diaphragmatic hernia

- Clinically apparent bleeding; thrombocytopenia <30,000 or other laboratory evidence
of coagulopathy

- Currently on ECMO or plan to initiate ECMO within 2 hours of enrollment