Purpose: The evidence supporting the benefit on clinical outcomes of prone positioning during veno-venous extracorporeal membrane oxygenation (V-V ECMO) for acute hypoxemic respiratory failure remains inconclusive. We aimed to assess the association of prone positioning, compared to no prone positioning, with 28-day mortality and other clinical outcomes in different patient subgroups.

Methods: A systematic review and meta-analysis of randomized and non-randomized controlled trials (RCTs) using a random-effects model was conducted. An electronic database search up to September 1st, 2024 was performed (PROSPERO CRD42024517602). The RoB 2 and ROBINS-I tools were used for risk of bias assessments.

Results: We analyzed two RCTs and 20 non-RCTs (3,465 patients). Compared to no prone positioning, the use of prone positioning was associated with lower 28-day (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.42–0.98, p = 0.040, I2 = 66%, low certainty of evidence [CoE]) and hospital mortality (OR 0.67, 95% CI 0.54–0.83, p < 0.001, I 2 = 39%, low CoE), despite fewer 28-day ventilator-free days and longer ECMO duration. Younger age (p = 0.005), a higher sequential organ failure assessment (SOFA) score (p = 0.022), non-Covid-19 etiology (p = 0.003), and lower rates of prone positioning before cannulation (p = 0.049) were associated with a greater benefit from prone positioning.

Conclusion: In this analysis, among patients supported with V-V ECMO for acute hypoxemic respiratory failure, we observed improved 28-day and hospital mortality in those who received prone positioning, compared to those who did not. However, these findings do not imply causation. Further research is needed to clarify the role of prone positioning in this population.