A critical appraisal of a randomized controlled trial: Willson et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury (JAMA 2005, 293: 470-476).

OBJECTIVE: To evaluate the use of exogenous surfactant in pediatric acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in decreasing the duration of respiratory failure.

DESIGN: A critical appraisal of a randomized controlled trial.

FINDINGS: This was a multiple-center, randomized, double-blinded, placebo-controlled trial evaluating the effect of calfactant via endotracheal tube in pediatric ALI/ARDS. The primary outcome was duration of respiratory failure measured by ventilator-free days at 28 days. Secondary outcomes included hospital course, adverse events, and failure of conventional mechanical ventilation (use of high-frequency oscillatory ventilation, inhaled nitric oxide, or extracorporeal membrane oxygenation). One hundred and fifty-two patients were enrolled and randomized with strict inclusion and exclusion criteria. Aside from the experimental interventions, the treatment and placebo groups were similar at baseline. Ventilator management guidelines were defined a priori. No significant difference in ventilator-free days was found, although the treatment group had a greater improvement in oxygenation. Mortality rate was significantly greater in the placebo group (relative risk, 1.9; 95% confidence interval, 1.1-3.2). However, when controlled for immunocompromised status, the statistical significance is lost. Subgroup analysis of infants showed a greater effect on mortality (relative risk, 3.3; 95% confidence interval, 1.1-10.5) and a significant difference in ventilator-free days (15.2 days vs. 7.0 days, p = .01) for the placebo group. No other differences in measured outcomes were seen. The treatment group had an increased rate of hypotension and transient hypoxia but not of airleaks or nosocomial pneumonias.

CONCLUSIONS: This is a well-designed study with an appropriate intention-to-treat analysis, but it is underpowered, making it difficult to identify which patients with pediatric ALI/ARDS might benefit from calfactant. Given the uncertainty of the benefits, calfactant cannot be routinely recommended in pediatric ALI/ARDS.