Intensive Care Med (2007) 33:680–688 DOI 10.1007/s00134-007-0545-y P E D I A T R I C O R I G I N A L Casper W. Bollen Cuno S. P. M. Uiterwaal Adrianus J. van Vught Meta-regression analysis of high-frequency ventilation vs conventional ventilation in infant respiratory distress syndrome Received: 10 January 2007 Accepted: 11 January 2007 Published online: 24 February 2007 © Springer-Verlag 2007 Electronic supplementary material The online version of this article (doi:10.1007/s00134-007-0545-y) contains supplementary material, which is available to authorized users C. W. Bollen ( ) · A. J. van Vught University Medical Center Utrecht, Pediatric Intensive Care Unit, 85090, 3508 AB Utrecht, The Netherlands e-mail: c.w.bollen@umcutrecht.nl Tel.: +31-30-2504002 Fax: +31-30-2505340 C. S. P. M. Uiterwaal University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, 85500, 3508 GA Utrecht, The Netherlands Abstract 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 hetero- geneity: 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 ventila- tion 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. Keywords Conventional mechanical ventilation · High-frequency ventila- tion · Meta-regression analysis · Res- piratory distress syndrome · Infant Introduction with infant respiratory distress syndrome (IRDS), adult respiratory distress syndrome (ARDS), and other forms of High-frequency ventilation (HFV) has been compared severe lung disease [1]. with conventional mechanical ventilation (CMV) since The HFV has been extensively investigated in prema- the 1980s. In HFV, patients are ventilated with small tidal ture neonates with IRDS, a population speciﬁcally at risk volumes, even smaller than the dead space of their air- for chronic lung disease (CLD). Unfortunately, the results ways, at high frequencies, normally between 5 and 10 Hz. of these studies were equivocal [2, 3]; thus, the question Because HFV combines high mean airway pressures with remains whether or not HFV better prevents CLD than small tidal volumes, this technique of ventilation has been conventional mechanical ventilation (CMV) in patients regarded by some to be the most optimal form in patients with severe lung disease. A signiﬁcant number of meta-