High-frequency oscillatory ventilation doesn’t improve and may actually worsen moderate to severe acute respiratory distress syndrome in adults, compared with standard ventilation, according to two reports published online Jan. 23 in the New England Journal of Medicine.
In two large, separate, randomized controlled trials comparing the two ventilation strategies, 1-month mortality in critically ill adults with ARDS who received high-frequency oscillatory ventilation (HFOV) was either higher or not significantly different from that in patients who received standard low tidal volume and high positive end–expiratory pressure ventilation.
Dr. Niall D. Ferguson
In one study, which was terminated early because of the large discrepancy in short-term mortality, HFOV also was associated with higher mean airway pressures and significantly greater need for sedatives, neuromuscular blockers, and vasoactive drugs.
Both trials call into question the current widespread use of HFOV early in the course of ARDS when patients don’t show an adequate response to conventional mechanical ventilation, the two research groups noted.
HFOV, which delivers very small tidal volumes at very high rates, is thought to minimize the lung damage done by ventilation’s repeated forced opening and collapsing of lung structures. Many clinicians now use it earlier in the course of ARDS, even though there are other approaches for improving oxygenation, based solely on the results of animal studies and small trials that used outdated ventilation methods as a control. The commercial availability of HFOV equipment has accelerated this trend.
In the absence of good evidence of HFOV’s effectiveness, experts in Canada and the United Kingdom called for rigorous randomized controlled trials.
Dr. Niall D. Ferguson and his associates in the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) trial compared the two strategies in patients aged 16-85 years who had moderate to severe ARDS and were treated at 39 intensive care units in Canada, Saudi Arabia, the United States, Chile, and India.
The OSCILLATE steering committee terminated the trial early, after only 548 subjects had been randomized, because three consecutive interim analyses showed that 1-month mortality was consistently higher with HFOV. "The effect size was sufficiently large that we concluded that even if early HFOV did not increase mortality, it would be very unlikely to decrease mortality," wrote Dr. Ferguson of the division of critical care medicine and the departments of medicine and physiology, University of Toronto, and his colleagues.
At that time, 1-month mortality was 47% for HFOV (129 of 275 patients), compared with 35% (96 of 273 patients) in the control group (N. Engl. J. Med. 2013 Jan. 23 [doi:10.1056/NEJMoa1215554]).
This result remained robust in three further analyses of the data that controlled for numerous variables. It also persisted in several subgroup analyses, regardless of the subjects’ baseline severity of hypoxemia, the subjects’ BMI, the use or nonuse of vasopressors, or the level of experience with ventilation at each medical center.
In addition, the use of vasopressors, which had been equivalent between the two study groups at baseline at approximately 63%, increased in the HFOV group to 73% within 4 hours of beginning the procedure and to 78% the next day. In contrast, vasopressors were used in only 62% and 58%, respectively, in the control group.
The use of neuromuscular blockers followed the same pattern, increasing in the HFOV group from 27% at baseline to 46% at 4 hours and 46% at 24 hours but remaining more steady in the control group at 29%, 31%, and 26%, respectively, they reported.
Cumulatively, vasoactive agents were used in 91% and neuromuscular blockers in 83% of the HFOV group, compared with 84% and 68%, respectively, in the control group. Vasoactive agents were required for an average of 2 days longer in the HFOV group, and neuromuscular blockers were required for an average of 1 day longer, compared with the control group.
Sedatives and opioids (primarily midazolam and fentanyl) were given for the same duration to the two study groups, but doses were higher in the HFOV group.
"Our results raise serious concerns about the early use of HFOV for the management of ARDS in adults. The results of this study increase the uncertainty about possible benefits of HFOV even when applied in patients with life-threatening refractory hypoxemia," Dr. Ferguson and his associates said.
In the Oscillation in ARDS (OSCAR) study, commissioned by the U.K.’s National Institute for Health Research, two ventilation techniques were compared in 795 patients in general ICUs at 12 university hospitals, 4 university-affiliated hospitals, and 13 district general hospitals in England, Wales, and Scotland.
As this was a pragmatic study meant to reflect real-world practice, HFOV was compared against whatever conventional ventilation was used in local practice, and the ICUs were "encouraged" to use the recommended combinations of positive end-expiratory pressure and fraction of inspired oxygen values. Consequently, management of the control group varied greatly from one ICU to the next, according to the researchers, led by Dr. Duncan Young of John Radcliffe Hospital and the University of Oxford, both in Oxford.