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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


American Journal of Respiratory and Critical Care Medicine


American Thoracic Society

Publication Date



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