Pharmacology of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn and Suboptimal Response to Inhaled Nitric Oxide*

@article{McNamara2013PharmacologyOM,
  title={Pharmacology of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn and Suboptimal Response to Inhaled Nitric Oxide*},
  author={Patrick J. McNamara and Sandesh P Shivananda and Mohit Sahni and David Freeman and Anna Taddio},
  journal={Pediatric Critical Care Medicine},
  year={2013},
  volume={14},
  pages={74–84}
}
Objectives: Persistent pulmonary hypertension of the newborn is a common problem with significant morbidity and mortality. Inhaled nitric oxide is the standard care, but up to 40% of neonates are nonresponders. Milrinone is a phosphodiesterase III inhibitor which increases the bioavailability of cyclic adenosine monophosphate and has been shown to improve pulmonary hemodynamics in animal experimental models. The primary objective was to investigate the pharmacological profile of milrinone in… Expand
Milrinone Pharmacokinetics and Pharmacodynamics in Neonates with Persistent Pulmonary Hypertension of the Newborn
TLDR
The CL of milrinone in newborns with PPHN is reduced and increases with age, and the addition of age improved the precision of the CL estimate, and CL increased with chronological age in days. Expand
The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension
TLDR
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. Expand
Milrinone Use in Persistent Pulmonary Hypertension of the Newborn.
TLDR
The pathophysiology of P PHN is discussed, the use of inotropic, lusitropic, and vasoactive agents in the management of PPHN is reviewed, with particular attention to milrinone. Expand
Treatment of Persistent Pulmonary Hypertension of the Newborn: Use of Pulmonary Vasodilators in Term Neonates
TLDR
Thorough review of available data informing efficacy and adverse effects contributes to the development of an informed approach to neonates with refractory PPHN, improving outcome in these infants. Expand
Pharmacologic strategies in neonatal pulmonary hypertension other than nitric oxide.
Inhaled nitric oxide (iNO) is approved for use in persistent pulmonary hypertension of the newborn (PPHN) but does not lead to sustained improvement in oxygenation in one-third of patients with PPHN.Expand
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
TLDR
This pilot study hypothesise that intravenous milrinone used in conjunction with iNO will result in a reduction in the time spent on iNO and lead to an improvement in myocardial performance and global hemodynamics when compared to iNO alone. Expand
Treatment of premature infants with pulmonary hypertension and right ventricular dysfunction with milrinone: a case series
TLDR
This case series suggests that milrinone may be a useful therapy for premature infants with echocardiography findings of PH and/or RH dysfunction, and support the need for a randomised control trial to confirm its efficacy. Expand
Persistent Pulmonary Hypertension of the Newborn: Pathophysiological Mechanisms and Novel Therapeutic Approaches
TLDR
Experimental evidence in PPHN animal models supports prospective use of emergent therapies, such as soluble guanylyl cyclase activators/stimulators, l-citrulline, Rho-kinase inhibitors, peroxisome proliferator-activated receptor-γ agonists, recombinant superoxide dismutase, tetrahydrobiopterin analogs, and recombinant human vascular endothelial growth factor (rhVEGF). Expand
Mini-symposium : Alveolar and Vascular Transition at Birth Diagnosis and management of persistent pulmonary hypertension of the newborn
Persistent pulmonary hypertension of new born (PPHN) is associated with mortality and morbidity; it may be idiopathic or secondary to a number of conditions. The mainstay of diagnosis and to excludeExpand
Advances in Neonatal Pulmonary Hypertension
TLDR
Investigation is likely to reveal new therapies such as citrulline and cinaciguat that will enhance NO synthase and soluble guanylate cyclase function, and prolonged exposure to iNO plus oxygen may activate phosphodiesterase (PDE) 3A. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 41 REFERENCES
Milrinone improves oxygenation in neonates with severe persistent pulmonary hypertension of the newborn.
TLDR
Intravenous milrinone produces early improvements in oxygenation without compromising systemic blood pressure and there was a nonsignificant trend toward improved blood pressure. Expand
Milrinone for persistent pulmonary hypertension of the newborn.
TLDR
The efficacy and safety of milrinone in the treatment of PPHN are not known and its use should be restricted within the context of RCTs. Expand
Neonatal Persistent Pulmonary Hypertension Treated with Milrinone: Four Case Reports
TLDR
Four cases with severe PPHN treated with a combination of iNO and Milrinone and substantial improvement in OI was followed by extubation and survival, however, of 4 patients, 2 developed serious intraventricular hemorrhages (IVHs), and 1 had a small IVH. Expand
Four patterns of response to inhaled nitric oxide for persistent pulmonary hypertension of the newborn.
TLDR
Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs. Expand
Persistent Pulmonary Hypertension of the Newborn in the Era Before Nitric Oxide: Practice Variation and Outcomes
TLDR
Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN and Randomized trials are needed to evaluate the role of these common therapies. Expand
Nitric oxide in respiratory failure in the newborn infant.
TLDR
Evidence is provided that INO improves oxygenation and reduces the need for ECMO in the near-term hypoxic neonate, but further research is required to evaluate the ultimate safety and benefit of this therapy. Expand
Milrinone: systemic and pulmonary hemodynamic effects in neonates after cardiac surgery.
TLDR
Administration of milrinone in neonates with low cardiac output after cardiac surgery lowers filling pressures, systemic and pulmonary arterial pressures, and systemic andmonary vascular resistances, while improving cardiac index. Expand
Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension
TLDR
Milrinone may have a selective pulmonary vasodilatory effect only in dogs with pulmonary hypertension, and an inhibition of platelet aggregation may decrease the MPAP resulting from an increase in cAMP caused by milrinone. Expand
Additive effects of inhaled nitric oxide and intravenous milrinone in experimental pulmonary hypertension
TLDR
Mrinone and INO both decrease pulmonary hypertension individually, and the combination produces additive effects, which may produce potent and selective pulmonary vasodilation during the treatment of pulmonary hypertension. Expand
Inhaled Nitric Oxide for the Early Treatment of Persistent Pulmonary Hypertension of the Term Newborn: A Randomized, Double-Masked, Placebo-Controlled, Dose-Response, Multicenter Study
TLDR
For term infants with PPHN, early I-NO as the sole adjunct to conventional management produced an acute and sustained improvement in oxygenation for 24 hours without short-term side effects, and the suggestion that ECMO use may be reduced. Expand
...
1
2
3
4
5
...