Some babies after PDA ligation develop a low cardiac output, Patrick McNamara and his colleagues have defined that as being less than 200 mL/kg/min left ventricular output. This cohort study of 30 infants post-ligation, by Afif El-Khuffash and colleagues at Sick Kids hospital in Toronto had 19 with low and 11 with normal cardiac output. El-Khuffash AF, Jain A, Weisz D, Mertens L, McNamara PJ. Assessment and Treatment of Post Patent Ductus Arteriosus Ligation Syndrome. The Journal of pediatrics. 2014. Using tissue doppler and speckle tracking they analyzed cardiac function, and they demonstrated that babies who had a lower cardiac output had increased systemic vascular resistance, and this was associated with signs of myocardial strain, in particular reduced systolic tissue velocities.
The authors then report that all the infants with low LVO were given milrinone, and this was followed by a reduction in SVR, an increase in LVO and an increase in systolic tissue velocities. Which of course begs the question, what happens if you don’t give them milrinone. The Sick Kids group are very pro-milrinone for these babies, but I remain unconvinced. They have not randomized babies to milrinone or control, and even if there is an effect of milrinone, it could all be explained by vasodilatation. Phosphodiesterase 3 inhibitors have variable effects in different animal neonatal models, with very poor or no inotropic effect, and even negative inotropic effects in some. Mary Paradisis’ randomized trial of milrinone in early life in very preterm babies showed no increase in perfusion, a reduction in blood pressure and a dilatation of the PDA, suggesting vasodilatation without improvements in cardiac function. Vasodilatation and reduction of afterload might be enough to explain the improvements in cardiac function and output.
It may be that at later postnatal ages the effects of milrinone may be different, but I think that needs to be proven, and even if vasodilatation is all that is needed in these infants to improve cardiac function, it might turn out that milrinone is a good way to vasodilate these babies; or maybe we should just wait and let them improve spontaneously; or maybe they should all get a touch of steroids; or maybe…. So many questions, so little time…
Here here. Milrinone is a drug looking for an indication in neonates. We need more randomised controlled evidence that there is a beneficial and important clinical effect before it comes into common use.