Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants

Chronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increase in compliance and tidal volume and decrease in pulmonary resistance have been documented with use of bronchodilators in studies of pulmonary mechanics in infants with CLD. Therefore, it is possible that bronchodilators might have a role in the prevention and treatment of CLD.

To determine the effect of bronchodilators given either prophylactically or as treatment for CLD on mortality and other complications of prematurity in preterm infants at risk for or having CLD.

For this update of the review, searches of The Cochrane Library, Issue 3, 2012; MEDLINE 1966; EMBASE; CINAHL; personal files and reference lists of identified trials were performed in March 2012. In addition Web of Science and abstracts from the Annual meetings of the Pediatric Academic Societies were searched electronically from 2000 to 2012 on PAS Abstracts2view(TM.) No language restrictions were applied.

Randomised controlled trials involving preterm infants were eligible for inclusion. Initiation of bronchodilator therapy had to occur within two weeks of birth for prevention of CLD. For treatment of CLD, treatment had to be initiated before discharge from the neonatal unit. The intervention had to include the administration of a bronchodilator either by nebulisation, metered dose inhaler (with or without a spacer device), intravenously or orally versus placebo or no intervention. Eligible studies had to include at least one of the predefined clinical outcomes (mortality, CLD, number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, any grade of intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), sepsis and adverse effects of bronchodilators. Adverse effects of bronchodilators included hypokalaemia, tachycardia, cardiac arrhythmias, tremor, hypertension and hyperglycaemia).

We used the standard method described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two investigators extracted and assessed all data for each study. We reported risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes and weighted mean difference (WMD) for continuous data.

In this update we identified four randomised controlled trials investigating the effects of bronchodilators in preterm infants. None of these studies fulfilled our inclusion criterion that clinical outcomes should be reported. One eligible study was previously found dealing with prevention of CLD; this study used salbutamol and enrolled 173 infants. No eligible studies were found dealing with treatment of CLD. Prophylaxis with salbutamol did not show a statistically significant difference in mortality (RR 1.08; 95% CI 0.50 to 2.31; RD 0.01; 95% CI -0.09 to 0.11) or CLD (RR 1.03; 95% CI 0.78 to 1.37; RD 0.02; 95% CI -0.13 to 0.17). No statistically significant differences were seen in other complications associated with CLD or preterm birth. No side effects due to salbutamol were commented on in this study.

There are insufficient data to reliably assess the use of salbutamol for the prevention of CLD. Further clinical trials are necessary to assess the role of salbutamol or other bronchodilator agents in prophylaxis or treatment of CLD. Researchers studying the effects of bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes.