Usefulness of surfactant for bronchiolitis in seriously ill infants and children

Review question
Will use of exogenous surfactant (a material made of lipid and protein that is produced by the lungs) in infants and children with bronchiolitis, who require mechanical ventilation, decrease mortality and duration of mechanical ventilation?

Background
Bronchiolitis (infection of small airways in the lungs) is one of the most common causes of respiratory failure in infants. There are no established treatment options for bronchiolitis. Surfactant may be useful in bronchiolitis because of its favourable effect on lung mechanics. We wanted to evaluate the efficacy of exogenous surfactant in reducing mortality and the duration of ventilation in infants and children with bronchiolitis, requiring mechanical ventilation.

Study characteristics
The evidence is current to June 2015. Three small randomised controlled trials (RCTs) enrolling 79 participants were included in the review. All studies included children younger than 2.5 years with a diagnosis of bronchiolitis who required mechanical ventilation. Two studies did not include a placebo (a substance having no active effect) for comparison. None of the included studies provided a source of funding.

Key results
Two included studies reported no mortality. Use of surfactant for mechanically ventilated infants and children with bronchiolitis did not decrease the duration of mechanical ventilation. However, the intervention decreased duration of stay in the intensive care unit and had favourable effects on oxygenation and carbon dioxide removal. No complications were observed in any of the three included studies.

Quality of the evidence
The level of evidence for duration of mechanical ventilation, duration of intensive care unit stay, oxygenation parameters, and carbon dioxide parameters was of moderate quality. The limited number of studies with small numbers of participants was the reason for moderate quality, and are limitations of this review. There is a need for larger trials to establish any benefits of surfactant for bronchiolitis in critically ill infants and children.

Authors' conclusions: 

Use of surfactant had favourable effects on duration of mechanical ventilation, duration of ICU stay, oxygenation, and CO2 elimination. However, the studies are few and small (n = 79) so 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.

Read the full abstract...
Background: 

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. This is an update of a review published in Issue 9, 2012. We did not identify any new studies for inclusion, and our conclusions remain unchanged.

Objectives: 

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.

Search strategy: 

We searched the Cochrane Central Register of Controlled Studies (CENTRAL; 2015, Issue 5) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1948 to June week 3, 2015); EMBASE (1974 to June 2015); CINAHL (1982 to June 2015); LILACS (1985 to June 2015); and Web of Science (1985 to June 2015).

Selection criteria: 

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.

Data collection and analysis: 

Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data, and performed meta-analyses.

Main results: 

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 reported no mortality. We judged all three of the included studies to be at low risk or unclear risk across all risk of bias categories; we did not judge any of the studies to be at high risk of bias in any category. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not significantly 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 CO2 elimination. No adverse effects and no complications were observed in any of the three included studies. The level of evidence for duration of mechanical ventilation, duration of intensive care unit stay, oxygenation parameters, and carbon dioxide parameters was of moderate quality.

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