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Ventilation strategies and outcome in randomised trials of high frequency ventilation

¹ Division of Neonatology and Pediatric Critical Care, University Hospital for Children and Adolescents, University of Ulm, Germany
² Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, AL, USA

Correspondence to:
Correspondence to:
Ulrich Thome
Division of Neonatology and Paediatric Critical Care, University Children’s Hospital, 89070 Ulm, Germany; ulrich.thome{at}gmx.net

Objective: Randomised controlled trials comparing elective use of high frequency ventilation (HFV) with conventional mechanical ventilation (CMV) in preterm infants have yielded conflicting results. We hypothesised that the variability of results may be explained by differences in study design, ventilation strategies, delay in initiation of HFV, and use of permissive hypercapnia.

Methods: Randomised controlled trials comparing the elective use of HFV with any form of CMV were identified. Trials were classified according to the ventilation strategies used for HFV and CMV and oscillator device employed. For cumulative meta-analyses, trials were arranged by the following covariables: mean duration until randomisation, Paco₂ limits, publication date, and sample size. Odds ratios (OR) and 95% confidence intervals were calculated using fixed and random effects models.

Results: Seventeen randomised trials enrolling 3776 patients were included. Unlike previous meta-analyses, there was no significant difference in the incidence of bronchopulmonary dysplasia or death (OR 0.87, 0.75–1.00) and severe intraventricular haemorrhage grade 3–4 (1.14, 0.96–1.37). The incidence of air leaks (OR 1.23, 1.06–1.44) was significantly increased with HFV. Subgroup analyses and cumulative meta-analyses demonstrated that trial results were related to the ventilation strategies used for HFV and CMV. No influence was found for mean time to randomisation, degree of permissive hypercapnia, or sample size.

Conclusions: Heterogeneity among trials of elective HFV compared to CMV in preterm infants is mainly due to differences in ventilatory strategies. Optimising CMV strategy appeared to be as effective as using HFV in improving pulmonary outcome in preterm infants.

Abbreviations: BPD28, bronchopulmonary dysplasia, defined as persistent requirement for supplemental oxygen or mechanical ventilation at a postnatal age of 28–30 days; BPD36, bronchopulmonary dysplasia, defined as persistent requirement for supplemental oxygen or mechanical ventilation at a postmenstrual age of 36–37 weeks; CMV, conventional mechanical ventilation; HFJV, high frequency jet ventilation; HFOV, high frequency oscillatory ventilation; HFPPV, high frequency positive pressure ventilation; HFV, high frequency ventilation; HLVS, high lung volume strategy; IVH 3–4, intraventricular haemorrhage grade 3 or 4; LLVS, low lung volume strategy; LPVS, low pressure volume strategy for CMV; OR, odds ratio; PVL, periventricular leukomalacia; RDS, respiratory distress syndrome

Keywords: bronchopulmonary dysplasia; high frequency ventilation; meta-analysis; preterm infant; review

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