Is Milrinone Safe and Effective for Infants with Congenital Diaphragmatic Hernia?

Pulmonary hypertension and related left ventricular dysfunction are common problems in congenital diaphragmatic hernia (CDH). Milrinone, a phosphodiesterase-3 inhibitor with lusitropic and vasodilator effects, is utilized in up to 30% of CDH cases nationwide. No randomized trials have tested efficacy or safety of milrinone in CDH infants. This retrospective cohort study compared neonates treated with milrinone to those not treated with milrinone. Sample included CDH infants treated at University of Utah and Primary Children's NICU from 1/2006-8/2017; excluded if diagnosed with associated severe congenital anomaly, chromosomal disorder, or treated with ECMO. Patients were organized into two groups: milrinone (attending discretion) and non-milrinone then paired by baseline oxygenation index (N=24 pairs). Efficacy and safety measures were evaluated at: baseline, 12-24 hours, 48-72 hours and 5-7 days. Analysis included frequency and serial changes of oxygenation (OI), ECHO characteristics of ventricular size, pulmonary artery systolic pressure (PASP), and adverse effects (non-operative bleeding, dysrhythmia, hypokalemia and thrombocytopenia). The resulting cohorts were of similar gestational age, birth weight, defect size, nitric oxide and hydrocortisone use; but MIL infants had a higher baseline PASP and more frequent bidirectional ductal shunt. Percent change in OI and PASP were similar over time between groups. Left ventricle measurements were lower in milrinone infants and did not significantly improve over time. Hypokalemia, thrombocytopenia, arrhythmia, and bleeding were not associated with milrinone therapy. This study does not support continued use of Milrinone; however, study limitations warrant prospective randomized controlled trials.