Background
Acute respiratory distress syndrome (ARDS) is a life-threatening condition. It is characterized by acute lung inflammation, stiff lungs that increase the work of breathing, and reduced ability of the lungs to adequately oxygenate the blood. Survivors can have a reduced quality of life. People with ARDS usually require an artificial respirator in order to prevent death. High-frequency oscillation (HFO) ventilation differs from conventional ventilation in that very small breaths are delivered very rapidly (180 to 900 breaths per minute). HFO helps with the opening of collapsed lung tissue by providing constant positive pressure in a person's airway. We performed a systematic review to determine whether HFO improves clinical outcomes (including preventing deaths) when compared to conventional breathing machines for adults and children with ARDS.
Study characteristics
We included 10 randomized controlled trials (RCTs) enrolling 1850 participants in this updated review. One large trial was stopped early because of increased deaths among participants who were randomized to HFO. Four trials reported at least some funding from manufacturers of HFO ventilators.
Key results
HFO did not reduce the risk of death in hospital in eight trials enrolling 1779 participants. The ability of the lungs to oxygenate blood, measured at 24 to 72 hours of ventilation after randomization, was 18% to 26% better in participants receiving HFO. HFO had no effect on the length of time an artificial breathing machine was required. The risk of unwanted side effects, including low blood pressure or further injury to the lung due to high airway pressure, was not increased.
Quality of the evidence
We found substantial inconsistency among clinical trials which reported the effect of HFO on the risk of death in participants with ARDS. The quality of evidence is very low for outcomes that would be most important to patients. This is because of a lack of precision and consistency, and because in many cases the methods used by investigators during clinical trials were not of the highest standard. This indicates that there is considerable uncertainty regarding the effect of HFO on death. Additional randomized trials could change these findings.
The findings of this systematic review suggest that HFO does not reduce hospital and 30-day mortality due to ARDS; the quality of evidence was very low. Our findings do not support the use of HFO as a first-line strategy in people undergoing mechanical ventilation for ARDS.
High-frequency oscillation (HFO) is an alternative to conventional mechanical ventilation that is sometimes used to treat people with acute respiratory distress syndrome, but effects on oxygenation, mortality and adverse clinical outcomes are uncertain. This review was originally published in 2004 and was updated in 2013 and again in 2015.
To determine the effects of HFO compared to conventional mechanical ventilation on physiological outcomes, clinical outcomes, and mortality when used for the treatment of acute respiratory distress syndrome (ARDS).
We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Ovid), MEDLINE (Ovid), EMBASE (Ovid), and ISI, from inception to December 2015. We conducted the original search in 2002. We manually searched reference lists from included studies and review articles; searched conference proceedings of the American Thoracic Society (1994 to 2015), Society of Critical Care Medicine (1994 to 2015), European Society of Intensive Care Medicine (1994 to 2015), and American College of Chest Physicians (1994 to 2015); contacted clinical experts in the field; and searched for unpublished and ongoing trials in clinicaltrials.gov and controlled-trials.com.
Randomized controlled trials (RCTs) comparing treatment using HFO with conventional mechanical ventilation for children and adults diagnosed with ARDS.
Three review authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. We used random-effects models in the analyses.
We include 10 RCTs (n = 1850); almost all participants had moderate or severe ARDS. For the primary analysis, the risk of bias was low in three studies and unclear in five studies; the overall quality of evidence was very low due to imprecision, inconsistency, indirectness and methodologic limitations. In participants randomized to HFO, there was no significant difference in hospital or 30-day mortality (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.72 to 1.16; P = 0.46, I² = 66%; 8 trials, 1779 participants, 807 deaths) compared with conventional ventilation. One large multicentre RCT was terminated early because of increased mortality in participants randomized to HFO compared to mechanical ventilation with low tidal volume and high positive end expiratory pressure, with HFO reserved only as a rescue therapy. We found substantial between-trial statistical heterogeneity (I² = 0% to 66%) for clinical outcomes, including mortality.