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November 13, 2018

Lessons From ARDS for Non-ARDS Research: Remembrance of Trials Past

Author Affiliations
  • 1Interdepartmental Division of Critical Care Medicine, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • 2Guy's and St Thomas' NHS Foundation Trust, ICU support Offices, St Thomas' Hospital, London, London, United Kingdom
  • 3Division of Infection, Immunity and Inflammation, Kings College London, United Kingdom
JAMA. 2018;320(18):1863-1865. doi:10.1001/jama.2018.14288

Perhaps the greatest bench-to-bedside success story in critical care medicine is the translation of laboratory observations of the mechanisms of ventilator-induced lung injury into successful clinical trials of strategies for mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). By 1993, there was consensus that a mechanical ventilation strategy targeting low tidal volumes and plateau pressures should reduce ventilator-induced lung injury in patients with ARDS, but that there was “no proof that any of these techniques alter the outcome of ARDS patients.”1 Five trials published between 1998 and 2000 tested variations of a lung-protective strategy; 3 produced negative results and 2 produced positive results.2 The positive trials used control group interventions with larger, potentially more injurious tidal volumes and the treatment group interventions used smaller, potentially more protective tidal volumes. The debate about whether an intermediate tidal volume would have been equally effective against an injurious control group intervention, or whether tidal volume is merely a surrogate for the correct target, such as mechanical power or driving pressure to attenuate lung injury, continues to this day.3 Nevertheless, a lung-protective ventilation strategy targeting a tidal volume of 6 mL/kg per body weight (PBW) is the current consensus recommendation for patients with ARDS.4