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Milrinone in persistent pulmonary hypertension of newborn: a scoping review

Pediatric Research (2024)Cite this article

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited.

Impact

  • Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy.

  • This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results.

  • Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy.

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Fig. 1: Flow diagram showing the selection of reports included in the review.

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Data availability

All data used in the review is already available in public domain.

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Author information

Author notes

  1. These authors contributed equally: Radu Galis, Diana Mudura.

Authors and Affiliations

  1. Department of Neonatology, Emergency County Hospital Bihor, Oradea, Romania

    Radu Galis, Diana Mudura & Paula Trif

  2. Department of Neonatology, Poznan University of Medical Sciences, Poznan, Poland

    Radu Galis, Jan Mazela & Boris W. Kramer

  3. Doctoral School of Biomedical Sciences, University of Oradea, Oradea, Romania

    Paula Trif

  4. Department of Paediatrics, Oyster Woman and Child Hospital, Bengaluru, India

    Shivashankar Diggikar

  5. University of Texas Southwestern, Dallas, TX, USA

    Arun Prasath

  6. Faculty of Medicine, Lucian Blaga University Sibiu, Sibiu, Romania

    Maria Livia Ognean

  7. Neonatology Department, Clinical County Emergency Hospital Sibiu, Sibiu, Romania

    Maria Livia Ognean

  8. Pediatrics Department, Bega Clinic, Emergency County Hospital Timisoara, Timișoara, Romania

    Adrian Lacatusu

  9. Victor Babes University, Timisoara, Romania

    Adrian Lacatusu

  10. Division of Neonatology, Cedars Sinai Guerin Children’s, Cedars Sinai Medical Center, Los Angeles, CA, USA

    Rangasamy Ramanathan

  11. Department of Pediatrics, Division of Neonatology, UC Davis Children’s Hospital, UC Davis Health, Sacramento, CA, USA

    Yogen Singh

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  1. Radu Galis
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  2. Diana Mudura
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  8. Adrian Lacatusu
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  9. Rangasamy Ramanathan
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Contributions

Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: R.G., Y.S. Drafting the article or revising it critically for important intellectual content: R.G., D.M., P.T., S.D., A.P., L.O., J.M., A.L., R.R., B.K., Y.S. All authors approved of the version to be published.

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Correspondence to Radu Galis.

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Galis, R., Mudura, D., Trif, P. et al. Milrinone in persistent pulmonary hypertension of newborn: a scoping review. Pediatr Res (2024). https://doi.org/10.1038/s41390-024-03234-z

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