Surfactant therapy for bronchiolitis in critically ill infants

Abstract

Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of evidence regarding effective treatment for bronchiolitis other than supportive care. Abnormalities of surfactant quantity or quality (or both) have been observed in severe cases of bronchiolitis. Exogenous surfactant administration appears to favourably change the haemodynamics of the lungs and may be a potentially promising therapy for severe bronchiolitis. To evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal administration of surfactant of any type (whether animal-derived or synthetic), at any dose and at any time after start of ventilation) compared to placebo, no intervention or standard care in reducing mortality and the duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation. We searched CENTRAL 2012, Issue 4 which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1948 to May week 1, 2012), EMBASE (1974 to May 2012), CINAHL (1982 to May 2012), LILACS (1985 to May 2012) and Web of Science (1985 to May 2012). We considered prospective, randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of exogenous surfactant in infants and children with bronchiolitis requiring mechanical ventilation. Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data and performed meta-analyses. We included three small RCTs enrolling 79 participants. Two trials did not use a placebo in the control arms and the third trial used air placebo. Two included studies did not describe mortality. We judged some of the included studies to have an unclear risk of bias but none of the included studies had a high risk of bias. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not different between the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but duration of intensive care unit (ICU) stay was less in the surfactant group compared to the control group: MD -3.31 (95% CI -6.38 to -0.25 days). After excluding one trial which produced significant heterogeneity, the duration of mechanical ventilation and duration of ICU stay were significantly lower in the surfactant group compared to the control group: MD -28.99 (95% CI -40.10 to -17.87 hours) and MD -1.81 (95% CI -2.42 to -1.19 days), respectively. Use of surfactant had favourable effects on oxygenation and CO(2) elimination. No adverse effects and no complications were observed in any of the three included studies. The available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. There is a need for larger trials with adequate power and a cost-effectiveness analysis to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care management.