Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis

Abstract

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Keywords: ARDS; PEEP; hypoxemic respiratory failure; lung recruitment maneuver; mortality.

Figure 1.

Summary of study retrieval and identification for network meta-analysis. ARDS = acute respiratory distress syndrome; LRM = lung recruitment maneuver; PEEP = positive end-expiratory pressure; Pes-guided = esophageal pressure–guided PEEP selection strategy.

Figure 2.

Network plots for the association of different positive end-expiratory pressure (PEEP) selection strategies with all-cause mortality. Network geometry shows nodes as interventions and each head to head direct comparison as lines connecting these nodes. The following strategies were not compared head to head in individual studies: 1) higher PEEP with prolonged lung recruitment maneuver (LRM) versus higher PEEP without LRM; 2) higher PEEP with brief LRM versus higher PEEP without LRM; 3) higher PEEP with prolonged LRM versus esophageal pressure–guided PEEP selection strategy (Pes-guided); and 4) higher PEEP with brief LRM versus Pes-guided. The size of the nodes is proportional to the number of participants in each node. The thickness of the connecting line is proportional to the number of randomized clinical trials in each comparison (depicted by the number beside line connecting nodes). The total number of participants by treatment strategy represents number of eligible patients included in the meta-analysis.

Figure 3.

Forest plot for the association of different positive end-expiratory pressure (PEEP) selection strategies with all-cause mortality. All outcomes are reported as network risk ratio (RR) or absolute risk difference with 95% credible interval (CrI). Posterior probabilities refer to the probability of an effect that is either protective (i.e., RR < 1.0 or absolute risk reduction [ARR] > 1%) or harmful (i.e., RR > 1.0). For estimating RRs for the comparison of the esophageal pressure–guided PEEP selection strategy (Pes-guided strategy) versus higher PEEP with brief or prolonged lung recruitment maneuver (LRM), and the higher PEEP strategy without LRM versus higher PEEP with brief or prolonged LRM, only indirect evidence was used because no direct pairwise comparisons were available. Between-study heterogeneity was assessed using the posterior distribution for τ (0.11 [95% CrI, 0.04–0.23]).

Figure 4.

Grading of recommendations assessment, development and evaluation network ranking and degree of certainty for the association of different positive end-expiratory pressure selection strategies with all-cause mortality. Dark blue represents high certainty of evidence; light blue represents moderate certainty of evidence; red represents low certainty of evidence. Posterior probabilities of benefit refer to the probability of any mortality benefit (i.e., risk ratio < 1). CrI = credible interval; LRM = lung recruitment maneuver; PEEP = positive end-expiratory pressure; Pes-guided = esophageal pressure–guided PEEP selection strategy.