Does a Higher Positive End Expiratory Pressure Decrease Mortality in Acute Respiratory Distress Syndrome? A Systematic Review and Meta-analysis

Background: Positive end expiratory pressure (PEEP) is an important component of therapy in patients with acute lung injury or acute respiratory distress syndrome. The independent effect of PEEP on mortality is currently unknown. Methods: A systematic review and meta-analysis of randomized controlled clinical trials comparing the use of higher and lower levels of PEEP. Results: Six trials with a total of 2,484 patients from 102 intensive care units and 9 countries met the eligibility criteria. In three trials, the effect of different levels of PEEP was compared in groups receiving comparable tidal volumes. Three trials accounted for more than 85% of total weighting in the meta-analyses. The pooled relative risk obtained from these three trials showed a trend towards improved mortality with high PEEP, even though the difference did not reach statistical significance: Pooled cumulative risk of 0.90 (95% CI 0.72-1.02, P = 0.077). The reduction in absolute risk of death was approximately 4%. There was no evidence of a significant increase in baro-trauma in patients receiving high PEEP, with a pooled risk of 0.95 (95% CI 0.62-1.45, P = 0.81). Conclusion: High PEEP strategy may have a clinically relevant independent mortality benefit. Despite a possible increase in baro-trauma, the benefits far outweigh potential risks. Current evidence therefore favors the use of high PEEP as the preferred option when ventilating patients with severe acute respiratory distress syndrome. As the reduction in absolute risk of death is less than 5%, a future clinical trial aimed at demonstrating statistical significance is likely to pose considerable financial and ethical burdens.