Early volume expansion versus inotrope for prevention of morbidity and mortality in very preterm infants

Abstract

Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. In very preterm infants, to determine the effect of early volume expansion compared to inotrope in reducing morbidity and mortality. Subgroup analysis was planned according to method of diagnosis of poor perfusion, postnatal age of treatment and type of volume expansion and inotrope used. The standard search strategy of the Cochrane Neonatal Review Group was used. All randomised trials that compared volume expansion to an inotrope in preterm infants in the first days of life were included. Data were extracted independently by each author and analysed using the standard methods of the Cochrane Collaboration and its Neonatal Review Group using relative risk (RR), risk difference (RD) and weighted mean difference (WMD). Two small studies comparing volume expansion, using albumin, with dopamine were included. Both studies were adequately randomised, unblinded studies of albumin versus dopamine with no losses to follow up and analysed by intention to treat. Data for clinical outcomes were available from one study in hypotensive preterm infants in the first day of life. In this study, albumin had a higher failure rate for correcting hypotension (RR 5.2, 95% CI 1.3, 20.6). As 49% of these infants had already been given volume, the question of which treatment should be given first was not answered. A second study compared albumin with dopamine in preterm infants with a normal mean blood pressure at a mean age of 32 hours. Dopamine produced a significant increase in mean blood pressure when compared to infants who received albumin or no treatment, although the difference between the dopamine and albumin groups did not reach significance. Albumin and dopamine produced similar increases in left ventricular output but no significant change in cerebral blood flow. No difference was found in mortality (RR 1.5, 95% CI 0.5, 4.0) or morbidity including any P/IVH, chronic lung disease or retinopathy. There was a higher rate of grade 2-4 P/IVH of borderline statistical significance in infants who received albumin in one study (RR 1.47; 95% CI 0.96 to 2.25: RD 0.27, 95% CI 0.00 to 0.54). No data were available for neurodevelopmental outcomes. Dopamine was more successful than albumin at correcting low blood pressure in hypotensive preterm infants, many of whom had already received volume. Neither intervention has been shown to be superior at improving blood flow, or in improving mortality and morbidity in preterm infants. The trials do not allow any firm conclusions to be made as to whether or when volume or dopamine should be used in preterm infants.