Association of different positive end-expiratory pressure selection strategies with all-cause mortality in adult patients with acute respiratory distress syndrome

Background: The acute respiratory distress syndrome (ARDS) has high morbidity and mortality. Positive end-expiratory pressure (PEEP) is commonly used in patients with ARDS but the best method to select the optimal PEEP level and reduce all-cause mortality is unclear. The primary objective of this network meta-analysis is to summarize the available evidence and to compare the effect of different PEEP selection strategies on all-cause mortality in adult patients with ARDS. Methods: We will search MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and LILACS from inception onwards for randomized controlled trials assessing the effect of PEEP selection strategies in adult patients with moderate to severe ARDS. We will exclude studies that did not use a lung-protective ventilation approach as part of the comparator or intervention strategy. The primary outcome will be all-cause mortality (at the longest available follow-up and up to 90 days). Secondary outcomes will include barotrauma, ventilator-free days, intensive care unit and hospital length of stay, and changes in oxygenation. Two reviewers will independently screen all citations, full-text articles, and extract study-data. We will assess the risk of bias for each of the outcomes using version 2 of the Cochrane risk of bias tool for randomized controlled trials. If feasible, Bayesian network meta-analyses will be conducted to obtain pooled estimates of all potential head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and risk differences, together with the associated 95% credible intervals. We will assess certainty in effect estimates using GRADE methodology. Discussion: The present study will inform clinical decision-making for adult patients with ARDS and will improve our understanding of the limitations of the available literature assessing PEEP selection strategies. Finally, this information may also inform the design of future randomized trials, including the selection of interventions, comparators, and predictive enrichment strategies. Trial registration: PROSPERO 2020 CRD42020193302.