# Can Milrinone Be a Therapeutic Alternative in Persistent Pulmonary Hypertension of the Newborn? A Case Series and Narrative Review

## TL;DR

This study explores milrinone as a possible treatment for newborns with persistent pulmonary hypertension when inhaled nitric oxide is not available, based on three cases and a literature review.

## Contribution

The study presents a case series and narrative review on milrinone's use in PPHN, highlighting its potential and risks in neonatal care.

## Key findings

- Milrinone improved oxygenation and heart function in term and late-preterm infants within 48 hours.
- Very preterm infants showed only temporary improvement and faced severe complications like bleeding.
- Milrinone may be a feasible alternative when iNO is unavailable but requires careful monitoring.

## Abstract

Background: Persistent pulmonary hypertension of the newborn (PPHN) remains a life-threatening condition resulting from failure of postnatal circulatory adaptation. Inhaled nitric oxide (iNO) is the standard first-line therapy; however, limited access or inadequate response highlight the need for alternative treatments. Milrinone, a selective phosphodiesterase-3 inhibitor with nitric oxide-independent vasodilatory and inotropic properties, has been proposed as one such option. Methods: In this study we present a case series of three neonates with PPHN—term (41 weeks), late preterm (35 weeks), and extremely preterm (23 weeks)—treated with intravenous milrinone in a neonatal unit without immediate access to iNO. A narrative literature review was also conducted, focusing on clinical outcomes, safety, and therapeutic applicability. Results: Milrinone was initiated within the first 24 h of life. In the term and late-preterm infants, oxygenation and echocardiographic parameters improved within 48 h, with normalization of shunt direction and successful extubation by days 4–10. Transient systemic hypotension occurred in both cases and required dose adjustment or vasoactive support. In the extremely preterm neonate, only temporary hemodynamic improvement was achieved, followed by severe intraventricular hemorrhage and coagulopathy, possibly exacerbated by vasodilatory and antiplatelet effects of milrinone. Conclusions: Milrinone may serve as a feasible adjunct or bridging therapy for PPHN when iNO is unavailable. However, its use requires careful hemodynamic and neurological monitoring, particularly in very preterm infants. Further studies are needed to confirm safety and define optimal dosing across gestational ages.