Critical & Organ Care · 2000
ARDSNet ARMA low tidal volume ventilation trial
Acute Respiratory Distress Syndrome Network, Acute Respiratory Distress Syndrome Mechanical ventilation Assessment trial
Through most of the 1990s, intensivists ventilated ARDS patients at tidal volumes of 10 to 15 mL per kilogram of body weight, a practice inherited from anesthesia and based on the goal of maintaining normal arterial carbon dioxide. The concept that the ventilator itself could worsen lung injury, by overdistending alveoli and triggering inflammatory cascades, had been described in animal models and by Arthur Slutsky's work on ventilator-induced lung injury, but translating that concept into a survival benefit in humans had proven elusive. Several small trials in the 1990s reached contradictory conclusions, and ARDS mortality had remained stubbornly near 40%.
The ARDSNet ARMA trial was sponsored by the National Heart, Lung, and Blood Institute and enrolled 861 patients with acute lung injury or ARDS at ten academic medical centers across the United States. Patients were randomized to ventilation at 12 mL per kilogram of predicted body weight or at 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 after the fourth planned interim analysis because the benefit crossed the prespecified stopping boundary.
Roy Brower chaired the steering committee and coordinated the multicenter effort. The decision to halt the trial early drew some criticism from investigators who had enrolled patients in the control arm, but the ethical obligation to stop when clear benefit was established was widely accepted. The result also settled a specific methodologic dispute: earlier negative trials had often compared 10 to 12 mL/kg against 7 to 8 mL/kg, and ARMA's more extreme separation between arms appeared necessary to detect the mortality signal.
Publication in the New England Journal of Medicine in May 2000 was followed by rapid adoption. Within months, major intensive care societies incorporated the 6 mL/kg protocol into their ARDS management guidance, and it was embedded in the Surviving Sepsis Campaign bundles when ARDS accompanied sepsis. The practical challenge of permissive hypercapnia, accepting the respiratory acidosis that lower tidal volumes produced, required adjusting practice in ICUs accustomed to normalizing all blood gas values.
The ARMA trial's deeper significance lay in demonstrating that a ventilator strategy, not a new drug or device, could cut mortality in a disease that had resisted pharmacologic intervention for decades. It also validated the ARDSNet model: a federally funded network capable of running adequately powered critical care trials in a patient population where enrollment is difficult and the window for intervention is short. That infrastructure subsequently supported trials of fluid management, transfusion thresholds, and positioning in ARDS.
Key People
- Roy Brower — Chair, ARDSNet ARMA steering committee
- Arthur Slutsky — Theorist of ventilator-induced lung injury whose work framed the hypothesis
- Gordon Bernard — ARDSNet investigator; co-author and Vanderbilt critical care leader
- Michael Matthay — UCSF co-investigator and ARDS pathophysiology researcher
N Engl J Med. 2000;342:1301-1308.
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