PDA closure

[mbayari]

Hi all
Have anyone heard about using Milrinone for PDA closure in preterm neonates? If so, waht's your policy? Thanks:rolleyes:

[JACK]

I really think it is quite impossible to use milrinone for PDA closure.

Milrinone is a PHOSPHODIESTERASE 3 INHIBITOR . It is a potent cardiac bipyridine with inotropic and vasodilator properties therefore, in the clinical setting, it has been frequently used to treat patients with heart failure. Milrinone exerts inotropic action through the mechanism inhibiting the breakdown of cAMP and, hence, elevating the cellular cAMP , which in turn activates cAMP-dependent protein kinases with a resultant increase in the transsarcolemmal influx of Ca and the rate of Ca uptake by the sarcoplasmic reticulum . Afterload reduction is also caused by milrinone. Milrinone is known to exert a vasodilating effect as well as positive inotropic and lusitropic effects.

Intravenous milrinone potentiates the pulmonary vasodilator effects of PGI(2) Prostacyclin.

Milrinone and Inhaled Nitric oxide both decrease pulmonary hypertension individually, and the combination produces additive effects. Combination therapy may produce potent and selective pulmonary vasodilation during the treatment of pulmonary hypertension. It is still a research drug for use in PPHN.

In rats, PDE 3 inhibitors reopen the constricted postnatal DA slightly. PDE 3 inhibitors dilate the fetal DA constricted with indomethacin effectively and more sensitively in preterm than in near-term fetuses.

Therefore, I believe it is not a drug for PDA closure; on the contrary it will facilitate ductal patency.

[Stefan Johansson]

...Milrinone for PDA closure in preterm neonates...

I guess you are referring to research done by a Sydney-based group (Evans, Kluckow and co-workers).
http://www.ncbi.nlm.nih.gov/pubmed/16690639

I personally find this group's research very interesting, since it challenges our current (old-fashioned) view on ductal shunting. For example - most consider shunting to be very small shortly after birth (due to high pulmonary vascular resistance) and increase with time, but this group has shown that shunting can be most severe during the first hours of life, resulting in low systemic blood flow (which in turn is strongly related to IVH. The strategy of "early targeted PDA closure" (in contrast to PDA prophylactic treatment) was suggested by this group.

The idea (as I understand it) is to give NSAID with Milrinone shortly after birth after low systemic is diagnosed with echocardiography,
1) to close the duct and
2) improve systemic blood flow

If I remember correctly there's a clinical trial (RCT) running in Australia. I do not know the alternative treatments infants are randomized to. But... I hope we will learn more about this strategy in the future. The knowledge of neonatal hemodynamics, ductal shunting and PDA treatment really needs to be further developed.

[mbayari]

Hi Stefan
That's exactly what I meant, referring to this paper I have reaad recently. I thought misunderstood what this team tried to learn us. Probably that the ongoing RCT will teach us more about such a deal. Thanks

[JACK]

Hi Stefan
That's exactly what I meant, referring to this paper I have reaad recently. I thought misunderstood what this team tried to learn us. Probably that the ongoing RCT will teach us more about such a deal. Thanks

I think your question should be rephrased as

"What is the role of milrinone in improving systemic blood flow in preterms?"

I think that is where the research is now stressing on.
Otherwise someone reading this thread may start using milrinone instead of indomethacin for PDA closure in preterms.

[JAMA]

I agree with JACK milrinone is not for PDA treatment.