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.