In the 1980s, a paradigm shift in the treatment of acute respiratory distress syndrome (ARDS) occurred: researchers found that decreasing tidal volumes provided by mechanical ventilation still allowed for adequate ventilation while, perhaps, avoiding excess lung injury. Based on this principle, high-frequency oscillatory ventilation (HFOV), which provides very small tidal volumes (1 to 2 ml per kilogram) at very high rates, was developed to treat ARDS. A few clinical trials with small patient populations have shown a beneficial effect of HFOV over conventional mechanical ventilation. The methods used for conventional mechanical ventilation treatment in those trials, however, are now outdated, and HFOV had not been tested in large populations… until now.
In this week’s issue of NEJM, two large, randomized trials challenge the previous data supporting the use of HFOV in the treatment of ARDS. In the OSCILLATE trial, investigators randomized 548 patients with moderate to severe ARDS across 39 centers in 5 countries. The patients were assigned to either HFOV therapy or conventional mechanical ventilation at a tidal volume of 6 ml per kilogram and relatively high levels of positive end-expiratory pressure (PEEP). The results were striking. In-hospital mortality was 47% in the HFOV treatment group, as compared to 35% in the control group (P=0.005). This finding was so significant that the trial was terminated early. In addition, more patients in the HFOV group received neuromuscular blockers and vasoactive drugs. Patients in the HFOV group also received higher doses of midazolam, a sedative. Overall, their results suggest that HFOV treatment is not beneficial for patients with ARDS, and may even be harmful.
The OSCAR trial further confirmed this conclusion. The group randomized 795 patients across multiple centers in England, Wales, and Scotland. The patients had moderate to severe ARDS, and were randomized to either the HFOV treatment group or the control group, in which the patients were treated with conventional-ventilation according to the standard protocol of the participating intensive care unit. The results showed that there was no significant difference between the two treatment groups, with 41.7% mortality in the HFOV group and 41.1% mortality in the control group (P=0.85). Patients in the HFOV group received neuromuscular-blockers and sedatives for longer than patients in the control group, but no other significant differences in their treatment or outcomes were observed. Yet again, HFOV did not demonstrate better outcomes.
Does this mean HFOV should never again be considered for treatment of ARDS? In an accompanying editorial, Atul Malhotra, MD and Jeffrey Drazen, MD, suggest that that may be too strong a conclusion. Although the trials clearly show that HFOV treatment was not effective using these protocols, Malhotra and Drazen suggest that perhaps other HFOV protocols may allow for the theoretical benefits of this treatment to be realized. In addition, they suggest that more careful patient selection may be important. For example, in patients with homogenous and recruitable lungs, HFOV treatment, which increases mean airway pressure, may be beneficial. In patients with heterogenous and nonrecruitable lungs, however, HFOV treatment may cause additional damage. Further studies are needed to evaluate which, if any, patient populations may benefit from HFOV treatment. But for now, it’s clear that this treatment is not as beneficial as it once seemed.