ARDSNet ARMA low tidal volume ventilation trial

Through most of the 1990s, intensivists ventilated ARDS patients at tidal volumes of 10 to 15 mL per kilogram of body weight. The idea that the ventilator itself could worsen lung injury came from animal work; in a 1997 rat-lung study from Arthur Slutsky's group in Toronto, high-volume ventilation without PEEP raised levels of the inflammatory cytokine TNF-alpha 56-fold. Turning that idea into a survival benefit in patients had proven elusive. Smaller trials in the 1990s had produced conflicting results.

The ARMA trial was run by the ARDS Network, which the National Heart, Lung, and Blood Institute had set up in 1994, and it enrolled 861 patients with acute lung injury or ARDS. The primary outcomes were death before a patient went home breathing without help, and ventilator-free days to day 28. Patients were randomized to an initial 12 mL per kilogram of predicted body weight with plateau pressure up to 50 cmH2O, or to 6 mL per kilogram with a plateau pressure ceiling of 30 cmH2O. Mortality was 39.8% in the high-volume arm and 31.0% in the low-volume arm. The trial was stopped early because mortality was lower in the low-volume group, which also had more ventilator-free days in the first 28 days (12 against 10).

The report was published under the network's name, with a writing committee led by Roy Brower of Johns Hopkins that included Michael Matthay, Alan Morris, David Schoenfeld, B. Taylor Thompson and Arthur Wheeler. The separation between arms was wide: mean tidal volumes over days 1 to 3 were 6.2 and 11.8 mL/kg, and mean plateau pressures 25 and 33 cmH2O.

The results appeared in the New England Journal of Medicine on May 4, 2000. The Surviving Sepsis Campaign guidelines of 2004 recommended low tidal volumes and limited plateau pressure, and a 2017 guideline from the American Thoracic Society and European and US critical care societies made lower tidal volumes a strong recommendation for all patients with ARDS. Bedside practice lagged: in a Baltimore cohort study published in 2012, only 41 percent of eligible ventilator settings met lung-protective targets.

ARMA showed that a change in ventilator settings, with no new drug or device, could lower mortality in ARDS. The network went on to run 10 randomized trials and one observational study before its contract ended in 2014. They included ALVEOLI in 2004, which found similar outcomes with higher or lower PEEP when tidal volume was held at 6 mL/kg, and FACTT in 2006, in which a conservative fluid strategy did not change 60-day mortality but shortened mechanical ventilation.