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

Eliza Wasilewska, Norbert Dera, Łukasz Minarowski, Łukasz Osinski, Anna Doboszynska, Sławomir Szajda, Alina Minarowska
Medical University of Gdańsk. Center of Postgraduate Medical Education. Warsaw Institute of Women’s Health. Medical University of Bialystok. University Teaching Hospital. Regional Specialist Hospital in Olsztyn. University of Warmia and Mazury in Olsztyn. University of Warmia and Mazury. Children’s University Hospital in Bialystok.
Poland

Pediatric Reports
Pediatr Rep 2025; 17:
DOI: 10.3390/pediatric17060116

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.

Category
Class I. Persistent Pulmonary Hypertension of the Newborn
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects

Age Focus: Pediatric Pulmonary Vascular Disease

Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication

Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes

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