Comparative Effectiveness of Protective Ventilation Strategies for Moderate and Severe Acute Respiratory Distress Syndrome. A Network Meta-Analysis

Choosing the best ventilation strategy for acute respiratory distress syndrome (ARDS) is complex, yet it is highly relevant to clinicians during a respiratory pandemic. To compare the effects of low Vt, high Vt, high positive end-expiratory pressure (PEEP), prone ventilation, high-frequency oscillation, and venovenous extracorporeal membrane oxygenation (VV ECMO) on mortality in ARDS. We performed a network meta-analysis of randomized trials. We applied the Grading of Recommendations Assessment, Development and Evaluation methodology to discern the relative effect of interventions on mortality. We analyzed 34 trials including 9,085 adults with primarily moderate-to-severe ARDS (median baseline Pa/Fi, 118; interquartile range, 110-143). Prone positioning combined with low Vt was the best strategy (risk ratio [RR], 0.74 [95% confidence interval (CI), 0.60-0.92] vs. low Vt; high certainty). VV ECMO was also rated among the best (RR, 0.78 [95% CI, 0.58-1.05] vs. low Vt; RR, 0.66; [95% CI, 0.49-0.88] vs. high Vt) but was rated with lower certainty because VV ECMO was restricted to very severe ARDS (mean baseline Pa/Fi<75). High PEEP combined with low Vt was rated intermediately (RR, 0.91 [95% CI, 0.81-1.03] vs. low Vt; low certainty; RR, 0.77 [95% CI, 0.65-0.91] vs. high Vt; moderate certainty). High Vt was rated worst (RR, 1.19 [95% CI, 1.02-1.37] vs. low Vt; moderate certainty), and we found no support for high-frequency oscillation or high Vt with prone ventilation. These findings suggest that combining low Vt with prone ventilation is associated with the greatest reduction in mortality for critically ill adults with moderate-to-severe ARDS.