"High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome"
The New England Journal of Medicine, 2013.

Clinical Question

Does early application of high-frequency oscillatory ventilation (HFOV) reduce mortality compared to a conventional low tidal volume and high PEEP ventilation strategy in adults with moderate-to-severe acute respiratory distress syndrome (ARDS)?

Bottom Line

In adults with moderate-to-severe ARDS, early application of HFOV does not improve, and may increase, in-hospital mortality compared to a conventional ventilation strategy of low tidal volume and high PEEP.

Major Points

Guidelines

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Guidelines at the time of study publication did not explicitly address the early use of HFOV in patients with ARDS.

Design

- Multicenter, randomized, controlled trial
- N=548 adults with new-onset, moderate-to-severe ARDS
- Intervention: HFOV (n=275)
- Control: Conventional ventilation with low tidal volumes and high PEEP (n=273)
- Primary outcome: Rate of in-hospital death from any cause
- Randomization stopped early on the recommendation of the data monitoring committee

Population

- Adult patients with new-onset, moderate-to-severe ARDS
- Inclusion criteria: Onset of pulmonary symptoms within past 2 weeks, intubation, hypoxemia, and bilateral air-space opacities on chest radiography
- Exclusion criteria included patients at risk for intracranial hypertension and other conditions limiting the duration of mechanical ventilation

Interventions

- HFOV group received median of 3 days of HFOV.
- Control group received conventional ventilation with the use of low tidal volumes and high PEEP.

Outcomes

- In-hospital mortality: 47% in the HFOV group, 35% in the control group (relative risk of death with HFOV, 1.33; P=0.005).
- Patients in HFOV group received higher doses of midazolam and more frequent use of neuromuscular blockers and vasoactive drugs.

Criticisms

- Trial stopped early, which may overestimate the effect size.
- Alternative HFOV protocols that use different mean airway pressures or oscillatory frequencies were not tested.

Funding

- Funded by the Canadian Institutes of Health Research and the King Abdullah International Medical Research Center.
- CareFusion loaned HFOV ventilators and provided technical support but had no role in other aspects of the trial.

Further Reading

- Supplementary information and a list of investigators are available at NEJM.org.