RATIONALE: High frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality. OBJECTIVES: The aim of this individual patient data meta-analysis was to identify ARDS patient subgroups with differential outcomes from HFOV. METHODS: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Pre-specified effect modifiers were tested using multi-variable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects. Measurements & Main Results: Data from 1552 patients in 4 trials were analyzed applying uniform definitions for study variables and outcomes. Patients had a mean baseline partial pressure of oxygen to fraction of inspired oxygen concentration ratio (PaO2:FiO2) of 114 (+39) mmHg; 40% had severe ARDS (PaO2:FiO2 <100 mm Hg). Mortality at 30 days was 321/785 (40.9%) for HFOV patients versus 288/767 (37.6%) for controls (adjusted odds ratio [OR], 1.17; 95% confidence interval [CI], 0.94-1.46; P=0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P=0.0003), with harm increasing with PaO2:FiO2 among mild-moderate ARDS patients, and the possibility of decreased mortality in very severe ARDS patients. Compliance and body-mass index did not modify the treatment effect. HFOV increased barotrauma risk compared to conventional ventilation (adjusted OR, 1.75; 95% CI 1.04-2.96; P=0.04). CONCLUSIONS: HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.

Original publication




Journal article


Am J Respir Crit Care Med

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acute respiratory distress syndrome, high frequency oscillatory ventilation, mechanical ventilation