ArticlesElective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data
Introduction
Despite advances in neonatal care, the risk of bronchopulmonary dysplasia remains high for very preterm infants1 and is associated with long-term neurodevelopmental delay and pulmonary impairment.2, 3 High-frequency oscillatory ventilation (HFOV) seems to be a promising technique for reduction of ventilator-associated lung injury in animals4 and, hence, could reduce risk of death or bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome. However, randomised controlled trials comparing elective HFOV with conventional ventilation have shown conflicting results.5, 6, 7, 8, 9, 10 Aggregate meta-analyses of trial data have been difficult to interpret because of heterogeneity in study design, patient characteristics, and outcome definition, and have limitations because interpretations are made on the basis of summary data extracted from published trial reports.11 Therefore, important questions about the use of HFOV in preterm infants remain unanswered, including whether some preterm infants benefit more or less from HFOV than others and whether the effect of HFOV is modified by factors such as the type of high-frequency ventilator and the time of initiation of ventilation. Consequently, the use of HFOV as the main method of ventilation in preterm infants with respiratory distress syndrome remains controversial.12
A meta-analysis based on original study data from randomised controlled trials of every individual patient could potentially address these unresolved issues.13 Information could be obtained for individual patients about the risk profile, details of how the study and co-interventions were done, and outcomes of interest. Variation in treatment effect according to the patient's risk profile and intervention-related effects could be explored.14 The Prevention of Ventilator Induced Lung Injury Collaborative Group (PreVILIG collaboration) was therefore formed with investigators of the randomised controlled trials to compare elective HFOV with conventional ventilation in preterm infants with respiratory failure, and a protocol was developed to undertake a systematic review with meta-analysis of individual patients' data.
Section snippets
Search strategy and selection criteria
The protocol of this report has been published,15 but is outlined here. We searched the most recent update of the Cochrane review of aggregate data (November, 2006),11 Medline, Embase, the Cochrane Controlled Trials Register (CENTRAL, Cochrane Library Issue 4, 2008), and the Oxford Database of Perinatal Trials using the MeSH terms “high-frequency ventilation” and “infant, premature”. We searched for reports written in any language from 2006, until January, 2009 (figure 1). We asked experts in
Results
We identified 18 trials that were eligible for inclusion, of which 15 were from the Cochrane review,5, 6, 7, 8, 9, 10, 20, 21, 22, 23, 24, 25, 26, 27, 28 two were from the updated search,29, 30 and one was unpublished (Texas Infant Star study, Texas Tech University School of Medicine, Odessa, TX, USA). We were unable to retrieve additional information or trace the original investigators from the unpublished trial. Thus, the 17 eligible trials reported a total of 3652 infants. In seven trials,
Discussion
Akin to the included studies, our meta-analysis of individual patients' data suggests that elective HFOV in preterm infants, compared with conventional ventilation, is equally effective in prevention of bronchopulmonary dysplasia without being associated with increased mortality or brain damage. Most secondary endpoints did not differ significantly between HFOV and conventional ventilation, although some evidence suggests an increase in rate of any pulmonary air leaks, and a decrease in patent
References (38)
- et al.
A comparison of summary patient-level covariates in meta-regression with individual patients' data meta-analysis
J Clin Epidemiol
(2002) - et al.
A multicenter randomized trial of high frequency oscillatory ventilation as compared with conventional mechanical ventilation in preterm infants with respiratory failure
Early Hum Dev
(1993) - et al.
A prospective, randomized, multicenter trial of high-frequency oscillatory ventilation compared with conventional ventilation in preterm infants with respiratory distress syndrome receiving surfactant
J Pediatr
(1998) - et al.
Randomized comparison of high frequency ventilation with high rate intermittent positive pressure ventilation in preterm infants with respiratory failure
J Pediatr
(1999) - et al.
Randomized trial of high-frequency oscillatory ventilation versus conventional ventilation: effect on systemic blood flow in very preterm infants
J Pediatr
(2003) - et al.
Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996
Pediatrics
(2001) - et al.
Early motor and mental development in very preterm infants with chronic lung disease
Arch Dis Child Fetal Neonatal Ed
(2000) - et al.
Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence
Pediatrics
(2006) - et al.
Lung volume maintenance prevents lung injury during high-frequency oscillatory ventilation in surfactant-deficient rabbits
Am Rev Respir Dis
(1988) - et al.
Prospective randomized comparison of high-frequency oscillatory and conventional ventilation in respiratory distress syndrome
Pediatrics
(1992)