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

Not enough evidence to show the effect of early volume expansion in very preterm babies. Low blood pressure and blood flow are common in preterm babies and can cause brain injury, organ damage and developmental problems. Increasing the amount of fluid in the blood stream (volume expansion) using albumin or salt solutions may increase the blood pressure and flow of blood. Inotrope drugs such as dopamine are used to increase the heart rate and blood pressure. The review of trials compared early volume expansion with inotropes. The review found dopamine is more effective than albumin at correcting low blood pressure in preterm babies but neither improves outcomes for babies. More research is needed.

Authors' conclusions: 

Dopamine was more successful than albumin at correcting low BP 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.

Read the full 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.


To determine the effect of early volume expansion compared to inotrope in reducing morbidity and mortality in very preterm infants. Subgroup analysis was planned according to method of diagnosis of poor perfusion, postnatal age of treatment and type of volume expansion and inotrope used.

Search strategy: 

Updated searches were performed of the Cochrane Central Register of Controlled Trials (Issue 3, 2008), MEDLINE (1996 - July 2008), EMBASE (1980 - July 2008), previous reviews including cross references, abstracts and conferences.

Selection criteria: 

All randomised trials that compared volume expansion to an inotrope in preterm infants born ≦ 32 weeks gestation or ≦ 1500 g in the first days after birth were included.

Data collection and analysis: 

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).

Main results: 

Two small studies comparing volume expansion (using albumin) with dopamine were included. Both studies were adequately randomised, unblinded studies of albumin vs. 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 after birth. In this study, albumin had a higher failure rate for correcting hypotension dopamine (RR 5.23; 95% CI 1.33 to 20.55). 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 (BP) at a mean age of 32 hours. Dopamine produced a significant increase in mean BP 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 1.45; 95% CI 0.53 to 3.95) 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.