Multivariate meta-analysis of the mortality effect of prone positioning in the acute respiratory distress syndrome

Background: The efficacy of prone positioning (PP) as therapy of the acute respiratory distress syndrome (ARDS) has varied in recent meta-analyses. The efficacy question was reviewed using a cohesive multivariate meta-analysis model incorporating all available common time-point data. Methods: Data from a core group of 8 randomized controlled trials (2001-2013) utilized in 8 current meta-analyses (2014-2017) was extracted for common time points. Multivariate meta-analysis and meta-regression models for prone-hours per day, mechanical ventilation tidal-volume and baseline patient PaO₂/FiO₂, considered as continuous and categorical predictors, determined the pooled relative risk (RR) of mortality for prone versus supine positioning. Results: Mortality RR at 28-30 days, 2-3 months and 6-months was not significant overall (P > 0.05). Meta-regression of categorical predictors indicated significant mortality reduction (P ≤ 0.001) for ≥ 12 prone-hours (versus < 12), lung protective ventilation (versus none) and moderate-severe ARDS (versus all ARDS). Meta-regressions of continuous predictors were also significant (P ≤ 0.021) and yielded treatment inflection points of efficacious therapy for ≥ 12 prone-hours per day, ≤ 8.5 mL/kg tidal volume and ≤ PaO₂/FiO₂ ratio of 130. Conclusions: The mortality treatment effect of PP in ARDS, was not demonstrated in the unadjusted meta-analysis model. Moderator effects indicated consistent significant benefit of prone positioning. In the absence of individual patient data, multivariate models provide more decisive conclusions than individual time point analyses.