Worsened short-term clinical outcomes in a cohort of patients with iNO-unresponsive PPHN: a case for improving iNO responsiveness

Abstract

Objectives To identify distinguishing characteristics of neonates with persistent pulmonary hypertension of the newborn (PPHN) unresponsive to inhaled nitric oxide (iNO) and evaluate the use of milrinone in this cohort. Study design Retrospective chart review of 99 neonates with PPHN treated with iNO over a five-year period at a quaternary neonatal intensive care unit. Results Neonates with iNO-unresponsive PPHN had an increased number of ventilator days (10 vs 7 days, p = 0.02), greater length of hospital stay (30 vs 22 days, p = 0.02), and increased risk of death or ECMO than iNO-responsive neonates (p = 0.03). Inhaled NO non-responders treated with milrinone had improved oxygenation (p < 0.03) and no change in systemic hemodynamics. Conclusion Neonates with iNO-unresponsive PPHN had worse clinical outcomes than iNO responders. Milrinone may be a safe and effective adjuvant therapy, although large-scale studies are lacking. Identifying early predictors of iNO response and novel strategies to enhance iNO responsiveness should be prioritized.