The use of milrinone in neonates with persistent pulmonary hypertension of the newborn - a randomised controlled trial pilot study (MINT 1): study protocol and review of literature

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is a relatively common condition which results in a mortality of up to 33%. Up to 40% of infants treated with nitric oxide (iNO) either have a transient response or fail to demonstrate an improvement in oxygenation. Milrinone, a selective phosphodiesterase 3 (PDE3) inhibitor with inotropic and lusitropic properties may have potential benefit in PPHN. This pilot study was developed to assess the impact of milrinone administration on time spent on iNO in infants with PPHN. This is a multicentre, randomized, double-blind, two arm pilot study, with a balanced (1:1) allocation of 20 infants. In this pilot study, we hypothesise that infants ≥34 weeks gestation and ≥ 2000 g with a clinical and echocardiography diagnosis of PPHN, intravenous milrinone used in conjunction with iNO will result in a reduction in the time spent on iNO. In addition, we hypothesise that milrinone treatment will lead to an improvement in myocardial performance and global hemodynamics when compared to iNO alone. We will also compare the rate of adverse events associated with the milrinone, and the pre-discharge outcomes of both groups. The purpose of this pilot study is to assess the feasibility of performing the trial and to obtain preliminary data to calculate a sample size for a definitive multi-centre trial of milrinone therapy in PPHN.Trial registration: www.isrctn.com; ISRCTN:12949496; EudraCT Number:2014–002988-16.Electronic supplementary materialThe online version of this article (10.1186/s40748-018-0093-1) contains supplementary material, which is available to authorized users.

Comprehensive Echocardiographic Assessment of Ventricular Function and Pulmonary Pressure in the Neonatal Omphalocele Population

“…36 There is currently lack of data in the newborn population, but this agent may become an interesting avenue to address patients with severe PH and underlying RV dysfunction leading to mortality. [36][37][38] Long-term evolution of PH in newborns with omphalocele remains unknown. Although some have suggested that PH resolves, 2 late PH has been described in some graduates of the NICU.…”

Is Milrinone Effective for Infants with Mild-to-Moderate Congenital Diaphragmatic Hernia?

“…In that regard, we note that only 33% of the infants in each group had OI > 10 and would be eligible for participation in ongoing/proposed randomized trials of milrinone in CDH or neonatal pulmonary hypertension. 17,18 Finally, our ability to interrogate cardiac performance was limited by a less than robust ECHO dataset. At our center, ECHO measures of right and left ventricular function are not routinely captured in a standardized manner for all neonates with CDH.…”

Can sonographic assessment of pulmonary vascular reactivity following maternal hyperoxygenation predict neonatal pulmonary hypertension? (HOTPOT study protocol)

“…A power calculation was performed for our study. Using an anticipated incidence of PPHN in a high risk cohort of 0.7% compared to a background incidence in the general population of 0.05% [ 24 ], 308 participants will be required for this study (80% confidence and a type I error rate of 0.05).…”