High-frequency oscillatory ventilation (HFOV) has been shown to improve oxygenation and survival in several small trials. Niall Ferguson and the OSCILLATE Trial Investigators, as well as researchers from the Canadian Critical Care Trials Group, performed a study to compare HFOV with a conventional ventilation strategy for patients with new-onset, moderate to severe acute respiratory distress syndrome (ARDS). Their results were published online January 22, 2013, in The New England Journal of Medicine.

Patients were enrolled from multiple centers in Canada, Saudi Arabia, Chile, India, and the United Statesfrom 2009 to 2012. They were eligible if they had acute ARDS with an Fio2 ≥0.5. All were started on pressure-controlled ventilation with tidal volumes of 6 mL/kg, Fio2 of 0.60, and positive end-expiratory pressure of 10 cm H2O. After 30 minutes, if the Pao2:Fio2 ratio remained at 200 or lower, patients underwent randomization to one of two groups. Those in the control group were treated with conventional ventilation targeting a tidal volume of 6 mL/kg and plateau pressure <35 cm H2O. In the intervention group, patients were treated with HFOV after a recruitment maneuver, targeting the highest possible frequency to maintain the Pao2 >55 mm Hg and pH above 7.25. The primary outcome was in-hospital mortality. Logistic regression was used to compare outcomes while adjusting for pre-specified baseline variables. A survival analysis was performed to compare the two groups with respect to the time of death.

After 548 patients had been enrolled, the study was terminated due to a higher rate of death in the HFOV group;  47% of patients in the HFOV group died compared with 35% in the control group (relative risk [RR] of death with HFOV, 1.33; 95% confidence interval [CI], 1.09-1.64; P=0.005). Over the course of the study, patients in the HFOV group required more vasopressors compared to the control group (91% vs. 84%, P<0.01) and more neuromuscular blockers (83% vs. 68%, P<0.001). Rates of co-interventions, such as steroids, prone positioning and dialysis, were similar in the two groups.

The authors concluded that among patients with moderate to severe ARDS, early application of HFOV was associated with higher mortality compared to a ventilation strategy that used small tidal volumes and high positive end-expiratory pressure. Previous positive HFOV trials have been scrutinized for the use of inferior and outdated ventilation modes in the comparator arms, as well as small sample sizes. In this trial, HFOV appeared to be associated with hemodynamic compromise, possibly due to the higher mean airway pressures associated with this modality. HFOV strategies that use lower mean airway pressures, different inspiratory-to-expiratory ratios, and lower oscillatory frequencies might lead to different results. Moreover, the sedation strategy used for HFOV may partially explain the disparate outcomes results. A very small proportion of trauma patients (n=15) were enrolled, and it is possible that HFOV may benefit other specific patient populations or patients with different risk factors for ARDS. It is not clear whether expertise with HFOV was uniform among the numerous international research sites. Based on the results of this study, HFOV may be best reserved for patients with refractory hypoxemia. Reliance on an established lung-protective strategy (i.e., ARDSNet-based) was demonstrated to be superior in this trial for the early treatment of moderate to severe ARDS.

Concise Critical Appraisal is a regular feature authored by SCCM member Samuel M. Galvagno Jr., DO, PhD. Each installment highlights journal articles most relevant to the critical care practitioner.