Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in...

Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 cycles per second. This has been shown to result in less lung injury in experimental studies.

The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation as compared to conventional ventilation (CV) in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease, without adverse effects.

Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in October 2002.

Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life.

The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. Treatment effects were expressed using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated. 95% confidence intervals were used.

Meta-analysis of the ten eligible studies comparing HFOV with CV revealed no evidence of effect on mortality at 28-30 days of age or at approximately term equivalent age. These results were consistent across studies. HFOV caused a significant reduction in CLD in survivors at term equivalent GA. However, the effect was not large in absolute terms [NNT 17 (10, 50)], and was inconsistent across studies. HFOV caused a significant reduction in the aggregated outcome, death or CLD at term equivalent GA. Again, however, the effect was not large [(NNT 20 (11, 100)] and was not consistent across studies. Pre-specified subgroup analyses according to use of a high volume strategy, or use of surfactant, did not identify subgroups in which there was evidence of effect on death, or in which the size of effect on CLD was substantially increased, or in which heterogeneity of treatment effect on CLD was removed. Short term neurological morbidity caused by HFOV was found in some studies, but this effect was not statistically significant overall. The subgroup of two trials not using a high volume strategy with HFOV found increased rates of Grade 3 or 4 IVH and of periventricular leukomalacia. An adverse effect of HFOV on longer term neurodevelopment was found in one large trial but not in two other small trials which reported this outcome.

There is strong evidence that HFOV had no significant effect on death as this result was consistent across trials. Although HFOV caused a modest reduction in CLD, this evidence is weaker, because of inconsistencies across trials in this effect. In general, subgroup analyses according to use of high volume strategy, or surfactant, did not remove this heterogeneity, which therefore remains largely unexplained. Any future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm), compare different strategies for generating HFOV and report important long term pulmonary and neurodevelopmental outcomes. Economic analysis should also be incorporated.