The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension

James, Adam; Corcoran, J D; McNamara, Patrick J.; Franklin, Orla; El-Khuffash, Afif

doi:10.1017/s1047951114002698

Cited by 67 publications

(40 citation statements)

References 36 publications

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“…Treatment of persistent pulmonary hypertension of newborn (PPHN) with milrinone requires further investigation although there are some case series papers that have found some benefits (fall in oxygenation index, decrease in the inhaled nitric oxide dose, an increase in blood pressure or an increase in indicators of myocardial performance) after milrinone infusion in newborn (term and preterm) infants with pulmonary hypertension [70][71][72][73][74].…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Drug Therapy for Human Newborn: Review of Pharmacodynamic Data

Ergenekon

Rojas-Anaya

Bravo

et al. 2018

CPD

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Background: Circulatory failure in preterm and term newborn infants is commonly treated with inotropes or vasoactive medications. In this structured literature review the available data on pharmacodynamic effects of the inotropes adrenaline, dobutamine, dopamine, levosimendan, milrinone, noradrenaline, and the vasoactive drugs vasopressin and hydrocortisone are presented. Methods: Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria which were human clinical trials published after 2000.Results: Out of 101 identified eligible studies only 22 studies met the criteria for evidence based practice guidelines level I to IV. The most prevalent pharmacodynamic effects were increase in blood pressure and/or heart rate, which were also the most frequently studied circulatory parameters. Conclusion: This review demonstrates the need for further systematic studies on all reviewed drugs with incorporation of novel noninvasive biomarkers in this vulnerable patient group, for more timely and appropriate treatment for clinical efficacy.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Drug Therapy for Human Newborn: Review of Pharmacodynamic Data

Ergenekon

Rojas-Anaya

Bravo

et al. 2018

CPD

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“…However, some animal studies have shown that high doses of dopamine will elevate both systemic and pulmonary vascular resistances, particularly if pulmonary vascular remodeling is present [34]. Milrinone, which inhibits phosphodiesterase (PDE) 3 (cAMP PDE) activity in cardiomyocytes and pulmonary arterial smooth muscle, is viewed as an ‘inodilator' that may be especially useful in the context of left ventricular dysfunction and pulmonary venous hypertension [35]. Since iNO inhibits PDE3 activity both in vitro and in vivo, milrinone may also be particularly effective as adjunctive therapy for iNO [36,37].…”

Section: Cardiac Supportmentioning

confidence: 99%

Advances in Neonatal Pulmonary Hypertension

Steinhorn¹

2016

Neonatology

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Persistent pulmonary hypertension of the newborn (PPHN) is a surprisingly common event in the neonatal intensive care unit, and affects both term and preterm infants. Recent studies have begun to elucidate the maternal, fetal and genetic risk factors that trigger PPHN. There have been numerous therapeutic advances over the last decade. It is now appreciated that oxygen supplementation, particularly for the goal of pulmonary vasodilation, needs to be approached as a therapy that has risks and benefits. Administration of surfactant or inhaled nitric oxide (iNO) therapy at a lower acuity of illness can decrease the risk of extracorporeal membrane oxygenation/death, progression of disease and duration of hospital stay. Milrinone may have specific benefits as an ‘inodilator', as prolonged exposure to iNO plus oxygen may activate phosphodiesterase (PDE) 3A. Additionally, sildenafil and hydrocortisone may benefit infants exposed to hyperoxia and oxidative stress. Continued investigation is likely to reveal new therapies such as citrulline and cinaciguat that will enhance NO synthase and soluble guanylate cyclase function. Continued laboratory and clinical investigation will be needed to optimize treatment and improve outcomes.

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“…Neonatologist performed TNE may play a pivotal role in the overall management of the neonate with suspected aPH through the timely and accurate diagnosis of PH, exclusion of PH mimics such as cyanotic congenital heart disease and objective evaluation of RV and LV function . Peterson et al reported the use of echocardiographic predictors of survival and necessity of ECMO, high‐frequency oscillatory ventilation (HFOV) and iNO in 63 neonates with pulmonary hypertension . They postulated that the early identification of at‐risk infants, using echocardiography markers, may prompt earlier or more aggressive intervention enabling enhanced patient outcome.…”

Section: Discussionmentioning

confidence: 99%

Accuracy and reliability of qualitative echocardiography assessment of right ventricular size and function in neonates

et al. 2019

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Background Subjective assessment of right ventricular (RV) function by neonatal echocardiography lacks validation. Incorrect diagnostic assignment in patients with suspected pulmonary hypertension (PH) may lead to unnecessary treatment or missed treatment opportunities. Methods Six evaluators (experts [n = 3], novice [n = 3]) were asked to independently rate RV characteristics (global function, dilation, and septal flattening) based on standardized echocardiography images. We randomly selected 60 infants, ≥35 weeks gestation at birth, of whom 30 were clinically unwell with acute pulmonary hypertension (aPH) and 30 were healthy controls. aPH was defined by echocardiography presence of right‐left shunting across transitional shunts or elevated right ventricular systolic pressure as estimated by the magnitude of the regurgitant jet across the tricuspid valve with impaired oxygenation. Inter‐rater comparative evaluation within groups and between groups was performed using Kappa statistics. Results Global agreement between evaluators for subjective assessment of RV function (0.3 [0.03], P < 0.001), size (0.14 [0.02], P < 0.001), and septal flattening (0.2 [0.02], P < 0.001) was uniformly poor. Agreement in RV function assessment was marginally better for both expert (0.32 [0.08], P < 0.001 vs 0.13 [0.081], and P < 0.001) and novice (0.4 [0.08], P < 0.001 vs 0.06 [0.07], and P < 0.001) evaluators. Overall, the diagnosis of aPH vs control was misclassified in 18% of cases. Conclusion This study demonstrated significant variability in qualitative assessment of RV size and function by trained evaluators, regardless of level of expertise attained. The reliability of objective measures of RV hemodynamics requires prospective evaluation.

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The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension

Abstract: The use of milrinone as an adjunct to nitric oxide is worth further exploration, with preliminary evidence suggesting an improvement in both oxygenation and myocardial performance in this group of infants.

Cited by 67 publications

References 36 publications

Cardiovascular Drug Therapy for Human Newborn: Review of Pharmacodynamic Data

Cardiovascular Drug Therapy for Human Newborn: Review of Pharmacodynamic Data

Advances in Neonatal Pulmonary Hypertension

Accuracy and reliability of qualitative echocardiography assessment of right ventricular size and function in neonates

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