REST Trial

What was the research question?

• Does the use of lower tidal volume facilitated by extracorporeal carbon dioxide removal improve 90-day mortality in acute hypoxemic respiratory failure receiving mechanical ventilation, compared with conventional low tidal volume ventilation?

How did they do it?

• Multicenter, randomized trial in 51 ICUs across the UK.

• 412 patients with acute respiratory failure and PaO2:FiO2 of <150 within the first 48 hours from onset of hypoxemia.

• Patients were randomized to receive lower tidal volume of ≤ 3mL/kg with extracorporeal CO2 removal (ECCO2R) or traditional tidal volume of 6 mL/kg.

• Primary outcome was in-hospital mortality and secondary were ventilator-free days at day 28, duration of invasive mechanical ventilation in survivors, need for ECMO up to day 7, ICU and hospital length of stay, mortality at day 28, and adverse event rate.

What did they find?

• In-hospital mortality rate was not statistically different between the two groups (41.5 vs 39.5, p=0.68).

• Fewer mean ventilator-free days in the ECCO2R group compared with the standard care group (7.1 vs 9, P = .02).

• Other secondary outcomes were not different between the two groups.

• Serious adverse events occurred more frequently in the ECCO2R group (31% vs 9%) and included intracranial hemorrhage (4.5% vs 0%), bleeding at other sites (3.0% vs 0.5%). Overall, 21 patients experienced 22 serious adverse events related to the study device.

Any limitation?

• The study was terminated early for futility therefore, it is underpowered.

• Inclusion was only 6% of screened patients, therefore difficult to generalize.

• Most of the sites were naïve to the use of ECCO2R.

• 8.4% of randomized patients to the ECCO2R group did not receive the intervention.

What does it mean?

• Despite the limitation of the study, the trial does not support the use of lower tidal volume/ECCO2R in early respiratory failure, and it might be harmful.