Corticosteroids for treating hypotension in preterm infants

Hafis Ibrahim, Ian P Sinha, Nimish V Subhedar, Hafis Ibrahim, Ian P Sinha, Nimish V Subhedar

Abstract

Background: Systemic hypotension is a relatively common complication of preterm birth and is associated with periventricular haemorrhage, 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.

Objectives: 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.

Search methods: Randomized or quasi-randomised controlled trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE (1996 to Jan 2011), EMBASE (1974 to Jan 2011), CINAHL (1981 to 2011), 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 to 2011).

Selection criteria: 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.

Data collection and analysis: 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 5.1.2. 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.

Main results: Four studies were included in this review enrolling a total of 123 babies. In one 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 two studies comparing steroid versus placebo, persistent hypotension (defined as a continuing need for inotrope infusion) was less common in steroid treated infants as compared to controls who received placebo for refractory hypotension (RR 0.35, 95% CI 0.19 to 0.65; RD -0.47, 95% CI - 0.68 to - 0.26; NNT = 2.1, 95% CI 1.47, 3.8). There were no statistically significant effects on any other short or long-term outcome. 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.

Authors' conclusions: Hydrocortisone may be as effective as dopamine when used as a primary treatment for hypotension. But the long term safety data on the use of hydrocortisone in this manner is unknown.Steroids are effective in treatment of refractory hypotension in preterm infants without an increase in short term adverse consequences. However, long term safety or benefit data is lacking. With long term benefit or safety data lacking steroids cannot be recommended routinely for the treatment of hypotension in preterm infants.