1. total length of mechanical ventilation (high-frequency and conventional combined),
2. length of stay in the intensive care unit,
3. length of hospital stay,
4. any long-term quality of life measurements,
5. any long-term cognitive measurements,
6. cost effectiveness.
1. 6-month mortality,
2. duration of mechanical ventilation (in days, as stated by the authors),
3. ventilator-free days to day 28 or 30 (in days, as stated by the authors),
4. health-related quality of life at one year,
5. treatment failure, leading to crossover to the other arm or discontinuation of the study protocol. We accepted authors’ definitions of treatment failure, which could include severe oxygenation failure, ventilation failure, hypotension, or barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema),
6. the ratio of partial pressure of arterial oxygen (PaO2) to inspired fraction of oxygen (FiO2) (PaO2/FiO2 ratio) at 24, 48, and 72 hours after randomization,
7. oxygenation index (OI, defined as 100 x mean airway pressure/PaO2/FiO2 ratio) measured at 24, 48, and 72 hours after randomization,
8. ventilation, measured by partial pressure of carbon dioxide (PaCO2) at 24, 48, and 72 hours after randomization,
9. mean airway pressure 24, 48, and 72 hours after randomization,
10. barotrauma (as stated by the authors),
11. hypotension (as stated by the authors),
12. endotracheal tube obstruction due to secretions,
13. technical complications and equipment failure in patients treated with HFO (including unintentional system air leaks, and problems with the oscillatory diaphragm, humidifier, and alarm systems).
Total duration of mechanical ventilation (1) is ambiguous may be measured in two ways in critical care trials: days of mechanical ventilation or ventilator free days. Since these endpoints cannot be combined we analysed them separately. We did not analyse length of ICU stay or hospital length of stay (2, 3) as these were likely to be confounded by mortality (an intervention that improves survival will also increase ICU or hospital length of stay). Long term quality of life measurements (4) and long term cognitive measurements (5) was not precisely defined and unlikely to be reported in studies to date. We chose to analyse health-related quality of life at one year, if reported.
We did not analyse cost-effectiveness (6) because it is unlikely cost-effectiveness studies would be performed since this intervention has not been yet proven to be effective.
We included several physiologic endpoints not in the original review in order to assess the effect of HFO on oxygenation (6,7) and ventilation (8,9).
We included several additional safety endpoints prior to undertaking this update in order to assess potential complications of HFO (10-13).