Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome

N Engl J Med. 2004 Jul 22;351(4):327-36. doi: 10.1056/NEJMoa032193.


Background: Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome (ARDS) receive positive end-expiratory pressure (PEEP) of 5 to 12 cm of water. Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention. We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients.

Methods: We randomly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels, which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen.

Results: Mean (+/-SD) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group (P<0.001). The rates of death before hospital discharge were 24.9 percent and 27.5 percent, respectively (P=0.48; 95 percent confidence interval for the difference between groups, -10.0 to 4.7 percent). From day 1 to day 28, breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group (P=0.50).

Conclusions: These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water, clinical outcomes are similar whether lower or higher PEEP levels are used.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Female
  • Hospital Mortality
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Positive-Pressure Respiration / methods*
  • Pulmonary Surfactant-Associated Protein D / blood
  • Respiratory Distress Syndrome / blood
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / physiopathology
  • Respiratory Distress Syndrome / therapy*
  • Respiratory Physiological Phenomena
  • Treatment Outcome


  • Biomarkers
  • Interleukin-6
  • Pulmonary Surfactant-Associated Protein D
  • Intercellular Adhesion Molecule-1