Multivariate Meta-Analysis of the Mortality Effect of Prone Positioning in the Acute Respiratory Distress Syndrome

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.

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.

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.

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.