Surfactant Therapy for Acute Respiratory Failure in Children
Introduction: Exogenous surfactant is used to treat acute respiratory failure in children, although the benefits and harms in this setting are not clear. The objective of the present systematic review is to assess the effect of exogenous pulmonary surfactant on all-cause mortality in children mechanically ventilated for acute respiratory failure.
Methods: We searched the MEDLINE, EMBASE, CINAHL and Ovid Healthstar databases, the bibliographies of included trials and review articles, conference proceedings and trial registries. We included prospective, randomized, controlled trials of pulmonary surfactant that enrolled intubated and mechanically ventilated children with acute respiratory failure. We excluded trials that exclusively enrolled neonates or patients with asthma. Two reviewers independently rated trials for inclusion, extracted data and assessed the methodologic quality. We quantitatively pooled the results of trials, where suitable, using a random effects model.
Results: Six trials randomizing 314 patients were included. Surfactant use reduced mortality (relative risk = 0.7, 95% confidence interval = 0.4 to 0.97, P = 0.04), was associated with increased ventilator-free days (weighted mean difference = 2.5 days, 95% confidence interval = 0.3 to 4.6 days, P = 0.02) and reduced the duration of ventilation (weighted mean difference = 2.3 days, 95% confidence interval = 0.1 to 4.4 days, P = 0.04).
Conclusion: Surfactant use decreased mortality, was associated with more ventilator-free days and reduced the duration of ventilation. No serious adverse events were reported.

Acute respiratory failure remains the primary indication for admission to North American paediatric intensive care units (PICUs) and accounts for significant mortality, morbidity and resource utilization. Respiratory infections, in particular pneumonia and severe bronchiolitis, are the most common causes of respiratory failure requiring mechanical ventilation in children.

Alterations in endogenous surfactant play a role in the pathogenesis of many causes of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Surfactant dysfunction, destruction and inactivation have also been demonstrated in children with acute respiratory insufficiency due to bronchiolitis. The administration of exogenous surfactant may reduce the need for mechanical ventilation and its associated sequelae by restoring surfactant levels and function. Inspired by the success of surfactants in reducing mortality and the need for mechanical ventilation in neonatal respiratory distress syndrome, investigators have studied exogenous surfactant in other populations with various causes of respiratory failure. Trials of surfactant in adults with ALI and ARDS have not demonstrated a mortality benefit, perhaps due to inherent differences in the aetiology of lung injury in adults, the design features of the trials, the mode and timing of surfactant administration or the type and dose of surfactant used. In children with respiratory failure, the efficacy of exogenous surfactant has been suggested in uncontrolled studies. The relatively low mortality rate, the diversity of the study populations and the shorter duration of mechanical ventilation are factors that make large-scale randomized controlled trials in this population challenging to conduct. Two of the largest trials were stopped early due to slower than expected enrolment. While the use of surfactant in ARDS/ALI has not been previously systematically reviewed, its use in children with bronchiolitis has been.

We anticipated that including trials enrolling children with acute respiratory failure from a variety of causes would result in a heterogeneous population and would increase the generalizability of the results. Our confidence in the results of the present review would also be increased if a consistent effect is shown in subgroups and across a spectrum of disease severity.

The primary objective of the systematic review is to assess the effect of the administration of pulmonary surfactant compared with no therapy or with placebo on all-cause mortality (at or before hospital discharge) in mechanically ventilated children with acute respiratory failure.