Elsevier

The Lancet

Volume 375, Issue 9731, 12–18 June 2010, Pages 2082-2091
The Lancet

Articles
Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data

https://doi.org/10.1016/S0140-6736(10)60278-4Get rights and content

Summary

Background

Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group.

Methods

We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes.

Findings

For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0·95 (95% CI 0·88–1·03), of death or severe adverse neurological event 1·00 (0·88–1·13), or any of these outcomes 0·98 (0·91–1·05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect.

Interpretation

HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids.

Funding

Nestlé Belgium, Belgian Red Cross, and Dräger International.

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

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