Corticosteroids for treating hypotension in preterm infants

Abstract

Systemic hypotension is a relatively common complication of preterm birth and is associated with periventricular haemmorhage, periventricular white matter injury and adverse neurodevelopmental outcome. Corticosteroid treatment has been used as an alternative, or an adjunct, to conventional treatment with volume expansion and vasopressor/inotropic therapy. To determine the effectiveness and safety of corticosteroids used either as primary treatment of hypotension or for the treatment of refractory hypotension in preterm infants. Randomized or quasi-randomized controlled trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005), MEDLINE (1996 - June 2005), EMBASE (1974 - June 2005), reference lists of published papers and abstracts from the Pediatric Academic Societies and the European Society for Pediatric Research meetings published in Pediatric Research (1995 - 2004). We included all randomised or quasi-randomised controlled trials investigating the effect of corticosteroid therapy in the treatment of hypotension in preterm infants (< 37 weeks gestation) less than 28 days old. Studies using corticosteroids as primary treatment were included as well as studies using corticosteroids in babies with hypotension resistant to inotropes/pressors and volume therapy. We included studies comparing oral/intravenous corticosteroids with placebo, other drugs used for providing cardiovascular support or no therapy in this review. Methodological quality of eligible studies was assessed according to the methods used for minimising selection bias, performance bias, attrition bias and detection bias. Studies that evaluated corticosteroids (1) as primary treatment for hypotension or (2) for refractory hypotension unresponsive to prior use of inotropes/pressors and volume therapy, were analysed using separate comparisons. Data were analysed using the standard methods of the Neonatal Review Group using Rev Man 4.2.7. Treatment effect was analysed using relative risk, risk reduction, number needed to treat for categorical outcomes and weighted mean difference for outcomes measured on a continuous scale, with 95% confidence intervals. Two studies were included in this review enrolling a total of 57 babies. In the first study, persistent hypotension was more common in hydrocortisone treated infants as compared to those who received dopamine as primary treatment for hypotension (RR 8.2, 95% CI 0.47 to 142.6; RD 0.19, 95% CI 0.01 to 0.37). In the second study, persistent hypotension (defined as a continuing need for epinephrine infusion) was less common in dexamethasone treated infants as compared to controls who received placebo for refractory hypotension (RR 0.42 , 95% CI 0.17 to 1.06; RD -0.51, 95% CI - 0.91 to - 0.12). There were no statistically significant effects on any other short or long-term outcome. It was not considered appropriate to perform a meta-analysis. A further two studies that have only been published in abstract form to date, may be eligible for inclusion in a future update of this review. There is insufficient evidence to support the routine use of steroids in the treatment of primary or refractory neonatal hypotension. Hydrocortisone may be as effective as dopamine in treating primary hypotension, but there are no data regarding the long-term safety of steroids used for this indication.A single dose of dexamethasone may be effective in treating preterm infants with refractory hypotension receiving epinephrine. However, given the lack of data on long-term safety dexamethasone cannot be recommended for routine use in preterm hypotension.