Meta-Analysis of Acute Lung Injury and Acute Respiratory Distress Syndrome Trials Testing Low Tidal Volumes

The use of low tidal volumes (5-7 ml/kg measured body weight) as a protective lung strategy is becoming widely recommended for patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (1-4). However, clinical trials testing low tidal volumes in ALI and ARDS have not shown uniform results (5-7). This has led some experts to recommend avoiding high tidal volumes during mechanical ventilation in these patients (6, 8), whereas other experts advocate using very low tidal volumes (1-4). Our concern, shared by others (9), was that trials showing low tidal volumes to be beneficial did not use control arms that reflected the current best practice standards at the time. Instead, the trials compared very low tidal volumes (5-7 ml/kg measured body weight) with traditional tidal volumes (10 ml/kg or more), which were higher than those routinely used (8-9 ml/kg) (10-13). As a result, those studies were inconclusive. We performed a meta-analysis to investigate why five randomized, prospective clinical trials produced disparate results and to critically evaluate the basis for recommending low tidal volume ventilation in ALI and ARDS (3-7). In this analysis, we demonstrate that there is a significant difference in the effects of low tidal volume on survival among the five trials. We then compare the tidal volumes and plateau airway pressures from the five trials to determine whether these account for differences in survival. In contrast to previous explanations based on the low tidal volumes tested (4), this meta-analysis demonstrates that significant differences in the control arms can account for the discrepant results among these five trials.