Effectiveness and safety of prolonged prone positioning in adult patients with acute respiratory distress syndrome (ARDS): a systematic review and meta-analysis.

BACKGROUND: Prolonged prone positioning (PPP) for ≥ 24 h may enhance outcomes in moderate to severe acute respiratory distress syndrome (ARDS), but may also increase risks such as pressure injuries and complications. Despite clinical rationale, high-quality evidence for PPP's safety and efficacy remains scarce. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) and observational studies. Trials that compared two distinct treatment groups in adult patients with ARDS were included: prone position < 24 h (standard) and ≥ 24 h (prolonged). Databases searched included MEDLINE, CENTRAL, ClinicalTrials.gov, ISRCTN, ICTRP and the Cochrane Covid-19 Study Register (last search: 3 July 2025). Risk of bias was assessed using ROB-2 for RCTs, and the ROBINS-I V2 tool for non-randomised intervention studies (NRSI). The primary outcome was mortality. Secondary outcomes included improvement of oxygenation and adverse events. Outcomes (Risk ratios and hazard ratios) were calculated using a random-effect model with 95% confidence intervals (CI). The quality of evidence was evaluated using the GRADE assessment. RESULTS: Of 19,986 records, 9 (n = 1,045) were included in the qualitative and quantitative analysis. Four studies, including two small RCTs (n = 112) and two NRSIs (n = 581), had a low to moderate risk of bias. Most studies included patients with COVID-19 ARDS. Meta-analysis showed no significant effect on 90-day mortality (n = 641, HR 0.72; 95% CI 0.41-1.25). No heterogeneity was detected among studies (I² = 0%), but the confidence interval for I² was wide (95% CI: 0-89%), suggesting the possibility that substantial heterogeneity may exist. Similarly, no significant differences were found for secondary outcomes. DISCUSSION: Current evidence does not support the use of PPP outside of clinical studies. Pooled data from small trials and NRSIs reveal no significant effect of PPP on mortality, oxygenation, or safety outcomes. The evidence is of low to very low certainty, limited by inconsistency and imprecision. The wide confidence intervals indicate low statistical power, therefore both harm and benefit remain plausible on the basis of the available evidence. Well-powered RCTs are needed to clarify the potential benefits and risks of PPP in ARDS.