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

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.