Randomized Trial of Milrinone Versus Placebo for Prevention of Low Systemic Blood Flow in Very Preterm Infants.

Author(s): Paradisis M, Evans N, Kluckow M, Osborn D

Affiliation(s): Department of Neonatal Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia; St Leonards, the Department of Newborn Care, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Camperdown, and the Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.

Publication date & source: 2008-09-24, J Pediatr., [Epub ahead of print]

OBJECTIVE: To assess the effectiveness of early prophylactic milrinone versus placebo for prevention of low systemic blood flow in high-risk preterm infants. STUDY DESIGN: Double-blind randomized placebo controlled trial of milrinone (loading dose 0.75 mug/kg/min for 3 hours then maintenance 0.2 mug/kg/min until 18 hours after birth) versus placebo. Infants born <30 weeks gestational age and <6 hours of age were eligible and were monitored with serial echocardiography, head ultrasound scanning, and continuous invasive blood pressure. Primary outcome was maintenance of superior vena cava (SVC) flow >/=45 mL/kg/min through the first 24 hours. The exit criterion was hypotension unresponsive to volume and inotropes. RESULTS: Ninety infants were enrolled, equal proportions maintained SVC flow >/=45 mL/kg/min after treatment commenced. No significant difference was observed in SVC flow, right ventricular output, and blood pressure during the first 24 hours; or grades 3 to 4 periventricular/intraventricular hemorrhage and death. Heart rate was higher and constriction of the ductus was slower in the infants randomized to milrinone. CONCLUSIONS: Milrinone did not prevent low systemic blood flow during the first 24 hours in very preterm infants, and no adverse effects were attributable to milrinone. Use of a preventative treatment with rescue model allowed comparison of an inotrope with placebo in this high-risk group of infants.