Objective: There is considerable heterogeneity among randomized trials comparing high-frequency ventilation (HFV) with conventional mechanical ventilation (CMV) in premature neonates with respiratory distress syndrome. We investigated what factors explained differences in outcome among these trials.
Design: Meta-regression analysis of 15 randomized trials.
Measurements and results: Variables were extracted to explain heterogeneity: year of publication; use of Sensormedics 3100A ventilator for HFV; time on CMV prior to start of study; gestational age; use of surfactant; high lung volume strategy in HFV; and lung protective ventilation strategy in CMV and baseline risk. Chronic lung disease (CLD) and death or CLD were outcome measures. Relative risk ratios were calculated to estimate effect sizes of explanatory variables on reported relative risks. Adjusted estimates of relative risk ratios of high lung volume strategy and lung protective ventilation strategy were 0.42 (95% CI 0.06-2.48) and 2.02 (95% CI 0.18-23.12) for CLD, respectively. The effect of gestational age was less pronounced (RRR=1.17 (95% CI 0.16-8.32) for CLD, respectively). Use of Sensormedics and prior time on CMV had the smallest effects [RRR=0.96 (95% CI 0.47-1.94) and RRR=0.85 (95% CI 0.58-1.24) for CLD, respectively)]. The same results applied to CLD or death as outcome.
Conclusions: Variation in ventilation strategies that were used in trials comparing HFV with CMV in premature neonates offered the most likely explanation for the observed differences in the outcome of these trials compared with other explanatory factors.