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Meta-Analysis
. 2015 Mar 19;2015(3):CD000104.
doi: 10.1002/14651858.CD000104.pub4.

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

Filip Cools  1 , Martin Offringa, Lisa M Askie
Affiliations
Meta-Analysis

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

Filip Cools et al. Cochrane Database Syst Rev. .

Abstract

Background: Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation (IPPV) in neonates with respiratory failure saves lives, its use is associated with lung injury and chronic lung disease. A newer form of ventilation called high frequency oscillatory ventilation has been shown in experimental studies to result in less lung injury.

Objectives: The objective of this review was to determine the effect of the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) on the incidence of chronic lung disease (CLD), mortality and other complications associated with prematurity and assisted ventilation in preterm infants who were mechanically ventilated for respiratory distress syndrome (RDS).

Search methods: Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conference and symposia proceedings; and from expert informants and handsearching of journals by The Cochrane Collaboration, mainly in the English language. The search was updated in January 2009 and again in November 2014.

Selection criteria: Randomised controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who required assisted ventilation. Randomisation and commencement of treatment needed to be as soon as possible after the start of CV and usually in the first 12 hours of life.

Data collection and analysis: The methodological quality of each trial was independently reviewed by the review authors. The standard effect measures were relative risk (RR) and risk difference (RD). From 1/RD the number needed to benefit (NNTB) to produce one outcome was calculated. For all measures of effect, 95% confidence intervals (CIs) were used. For interpretation of subgroup analyses, a P value for subgroup differences as well as the I(2) statistic for between-subgroup heterogeneity were calculated. Meta-analysis was performed using both a fixed-effect and a random-effects model. Where heterogeneity was over 50%, the random-effects model RR was also reported.

Main results: Nineteen eligible studies involving 4096 infants were included. Meta-analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28 to 30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The risk of CLD in survivors at term equivalent gestational age was significantly reduced with the use of HFOV but this effect was inconsistent across studies, even after the meta-analysis was restricted to studies that applied a high lung volume strategy with HFOV. Subgroup analysis by HFOV strategy showed a similar effect in trials with a more strict lung volume recruitment strategy, targeting a very low fraction of inspired oxygen (FiO2), and trials with a less strict lung volume recruitment strategy and with a somewhat higher or unspecified target FiO2. Subgroup analyses by age at randomisation, routine surfactant use or not, type of high frequency ventilator (oscillator versus flow interrupter), inspiratory to expiratory (I:E) ratio of high frequency ventilator (1:1 versus 1:2) and CV strategy (lung protective or not) could not sufficiently explain the heterogeneity. Pulmonary air leaks, defined as gross air leaks or pulmonary interstitial emphysema, occurred more frequently in the HFOV group, whereas the risk of severe retinopathy of prematurity was significantly reduced.Although in some studies an increased risk of severe grade intracranial haemorrhage and periventricular leukomalacia was found, the overall meta-analysis revealed no significant differences in effect between HFOV and CV. The short-term neurological morbidity with HFOV was only found in the subgroup of two trials not using a high volume strategy with HFOV. Most trials did not find a significant difference in long-term neurodevelopmental outcome, although one recent trial showed a significant reduction in the risk of cerebral palsy and poor mental development.

Authors' conclusions: There is evidence that the use of elective HFOV compared with CV results in a small reduction in the risk of CLD, but the evidence is weakened by the inconsistency of this effect across trials. Probably many factors, both related to the intervention itself as well as to the individual patient, interact in complex ways. In addition, the benefit could be counteracted by an increased risk of acute air leak. Adverse effects on short-term neurological outcomes have been observed in some studies but these effects are not significant overall. Most trials reporting long-term outcome have not identified any difference.

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Conflict of interest statement

None

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 1 Death by 28 to 30 days.
1.2
1.2. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 2 Mechanical ventilation at 28 to 30 days in survivors.
1.3
1.3. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 3 Oxygen at 28 to 30 days in survivors.
1.4
1.4. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 4 CLD at 28 to 30 days (O2 + x‐ray) in survivors.
1.5
1.5. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 5 Death or CLD at 28 to 30 days.
1.6
1.6. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 6 Death by 36 to 37 weeks or discharge.
1.7
1.7. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 7 CLD at 36 to 37 weeks PMA or discharge in survivors.
1.8
1.8. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 8 Death or CLD at 36 to 37 weeks PMA or discharge.
1.9
1.9. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 9 Any pulmonary air leak.
1.10
1.10. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 10 Gross pulmonary air leak.
1.11
1.11. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 11 Intraventricular haemorrhage ‐ all grades.
1.12
1.12. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 12 Intraventricular haemorrhage ‐ grades 3 or 4.
1.13
1.13. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 13 Periventricular leukomalacia.
1.14
1.14. Analysis
Comparison 1 HFOV versus CV (all trials), Outcome 14 Retinopathy of prematurity (stage 2 or greater) in survivors.
2.1
2.1. Analysis
Comparison 2 HFOV versus CV subgrouped by volume strategy on HFOV, Outcome 1 Death by 36 to 37 weeks or discharge.
2.2
2.2. Analysis
Comparison 2 HFOV versus CV subgrouped by volume strategy on HFOV, Outcome 2 CLD at 36 to 37 weeks PMA or discharge in survivors.
2.3
2.3. Analysis
Comparison 2 HFOV versus CV subgrouped by volume strategy on HFOV, Outcome 3 Death or CLD at 36 to 37 weeks PMA or discharge.
2.4
2.4. Analysis
Comparison 2 HFOV versus CV subgrouped by volume strategy on HFOV, Outcome 4 Gross pulmonary air leak.
2.5
2.5. Analysis
Comparison 2 HFOV versus CV subgrouped by volume strategy on HFOV, Outcome 5 Intraventricular haemorrhage ‐ grades 3 or 4.
2.6
2.6. Analysis
Comparison 2 HFOV versus CV subgrouped by volume strategy on HFOV, Outcome 6 Periventricular leukomalacia.
3.1
3.1. Analysis
Comparison 3 HFOV versus CV subgrouped by use of surfactant, Outcome 1 Death by 36 to 37 weeks or discharge.
3.2
3.2. Analysis
Comparison 3 HFOV versus CV subgrouped by use of surfactant, Outcome 2 CLD at 36 to 37 weeks PMA or discharge in survivors.
3.3
3.3. Analysis
Comparison 3 HFOV versus CV subgrouped by use of surfactant, Outcome 3 Death or CLD at 36 to 37 weeks PMA or discharge.
3.4
3.4. Analysis
Comparison 3 HFOV versus CV subgrouped by use of surfactant, Outcome 4 Gross pulmonary air leak.
3.5
3.5. Analysis
Comparison 3 HFOV versus CV subgrouped by use of surfactant, Outcome 5 Intraventricular haemorrhage ‐ grades 3 or 4.
3.6
3.6. Analysis
Comparison 3 HFOV versus CV subgrouped by use of surfactant, Outcome 6 Periventricular leukomalacia.
4.1
4.1. Analysis
Comparison 4 HFOV versus CV subgrouped by type of HFO ventilator, Outcome 1 Death by 36 to 37 weeks or discharge.
4.2
4.2. Analysis
Comparison 4 HFOV versus CV subgrouped by type of HFO ventilator, Outcome 2 CLD at 36 to 37 weeks PMA or discharge in survivors.
4.3
4.3. Analysis
Comparison 4 HFOV versus CV subgrouped by type of HFO ventilator, Outcome 3 Death or CLD at 36 to 37 weeks PMA or discharge.
4.4
4.4. Analysis
Comparison 4 HFOV versus CV subgrouped by type of HFO ventilator, Outcome 4 Gross pulmonary air leak.
4.5
4.5. Analysis
Comparison 4 HFOV versus CV subgrouped by type of HFO ventilator, Outcome 5 Intraventricular haemorrhage ‐ grades 3 or 4.
4.6
4.6. Analysis
Comparison 4 HFOV versus CV subgrouped by type of HFO ventilator, Outcome 6 Periventricular leukomalacia.
5.1
5.1. Analysis
Comparison 5 HFOV versus CV subgrouped by lung protective (LPS) CV strategy, Outcome 1 Death by 36 to 37 weeks or discharge.
5.2
5.2. Analysis
Comparison 5 HFOV versus CV subgrouped by lung protective (LPS) CV strategy, Outcome 2 CLD at 36 to 37 weeks PMA or discharge in survivors.
5.3
5.3. Analysis
Comparison 5 HFOV versus CV subgrouped by lung protective (LPS) CV strategy, Outcome 3 Death or CLD at 36 to 37 weeks PMA or discharge.
5.4
5.4. Analysis
Comparison 5 HFOV versus CV subgrouped by lung protective (LPS) CV strategy, Outcome 4 Gross pulmonary air leak.
5.5
5.5. Analysis
Comparison 5 HFOV versus CV subgrouped by lung protective (LPS) CV strategy, Outcome 5 Intraventricular haemorrhage ‐ grades 3 or 4.
5.6
5.6. Analysis
Comparison 5 HFOV versus CV subgrouped by lung protective (LPS) CV strategy, Outcome 6 Periventricular leukomalacia.
6.1
6.1. Analysis
Comparison 6 HFOV versus CV subgrouped by age at randomisation, Outcome 1 Death by 36 to 37 weeks or discharge.
6.2
6.2. Analysis
Comparison 6 HFOV versus CV subgrouped by age at randomisation, Outcome 2 CLD at 36 to 37 weeks PMA or discharge in survivors.
6.3
6.3. Analysis
Comparison 6 HFOV versus CV subgrouped by age at randomisation, Outcome 3 Death or CLD at 36 to 37 weeks PMA or discharge.
6.4
6.4. Analysis
Comparison 6 HFOV versus CV subgrouped by age at randomisation, Outcome 4 Gross pulmonary air leak.
6.5
6.5. Analysis
Comparison 6 HFOV versus CV subgrouped by age at randomisation, Outcome 5 Intraventricular haemorrhage ‐ grades 3 or 4.
6.6
6.6. Analysis
Comparison 6 HFOV versus CV subgrouped by age at randomisation, Outcome 6 Periventricular leukomalacia.
7.1
7.1. Analysis
Comparison 7 HFOV versus CV subgrouped by I:E ratio on HFOV, Outcome 1 Death by 36 to 37 weeks or discharge.
7.2
7.2. Analysis
Comparison 7 HFOV versus CV subgrouped by I:E ratio on HFOV, Outcome 2 CLD at 36 to 37 weeks PMA or discharge in survivors.
7.3
7.3. Analysis
Comparison 7 HFOV versus CV subgrouped by I:E ratio on HFOV, Outcome 3 Death or CLD at 36 to 37 weeks PMA or discharge.
7.4
7.4. Analysis
Comparison 7 HFOV versus CV subgrouped by I:E ratio on HFOV, Outcome 4 Gross pulmonary air leak.
7.5
7.5. Analysis
Comparison 7 HFOV versus CV subgrouped by I:E ratio on HFOV, Outcome 5 Intraventricular haemorrhage ‐ grades 3 or 4.
7.6
7.6. Analysis
Comparison 7 HFOV versus CV subgrouped by I:E ratio on HFOV, Outcome 6 Periventricular leukomalacia.
See this image and copyright information in PMC

Update of

References

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Moriette 2001 {published data only}
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Ogawa 1993 {published data only}
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Plavka 1999 {published data only}
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Salvo 2012 {published data only}
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References to studies excluded from this review

Cambonie 2003 {published data only}
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Froese 1987 {published data only}
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References to studies awaiting assessment

Elazeez 2010 {published data only}
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References to ongoing studies

Texas Infant Star {unpublished data only}
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References to other published versions of this review

Henderson‐Smart 1999
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