Higher versus lower positive end-expiratory pressure in acute lung injury and acute respiratory distress syndrome: systematic review and individual patient data meta-analysis

Introduction

Trials comparing higher versus lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) were underpowered to detect small but important effects on mortality, overall or in any subgroups.

Methods

We searched MEDLINE, Embase, and the Cochrane Central Register for trials randomly assigning adults with acute lung injury or ARDS to higher versus lower levels of PEEP (minimal difference of 3 cmH₂O over first 3 days), while using low tidal volume ventilation, and comparing mortality. Data from 2,299 individual patients in three trials were analyzed using uniform outcome definitions. We tested prespecified effect modifiers using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects.

Results

Overall, there were 374 hospital deaths (32.9%) in the higher PEEP group and 409 (35.2%) in the lower PEEP group (adjusted relative risk, 0.94; 95% confidence interval (CI), 0.86 to 1.04; P = 0.25). Treatment effects varied with the presence or absence of ARDS, defined by a ratio of partial pressure of oxygen to fractional inspired oxygen concentration equal to or less than 200 mmHg (interaction P = 0.02). The relative risks of hospital mortality for patients with and without ARDS were 0.90 (95% CI, 0.81 to 1.00, P = 0.049) and 1.37 (95% CI, 0.98 to 1.92, P = 0.065), respectively. Patients with ARDS were more likely to achieve unassisted breathing earlier (hazard ratio, 1.16 (95% CI, 1.03 to 1.30, P = 0.01); whereas the hazard ratio for time to unassisted breathing was 0.79 (95% CI, 0.62 to 0.99, P = 0.04) in patients without ARDS at baseline. Rates of pneumothorax and the use of neuromuscular blockers, vasopressors and corticosteroids were similar.

Conclusions

Higher levels of PEEP are likely to improve survival for patients with ARDS, but not for patients with less severe acute lung injury.