Abstract
Extracorporeal membrane oxygenation (ECMO) is increasingly utilized in refractory cardiogenic shock, though the optimal cannulation strategy remains debated, due to divergent vascular and bleeding complications. Peripheral (femoral) access offers ease of deployment but may increase limb ischemia risk, while central (aortic/right atrial) cannulation improves antegrade flow, but carries a higher surgical bleeding burden. We performed a meta-analysis to compare outcomes between peripheral and central cannulation, focusing on major complications, including bleeding, limb ischemia, infection, renal replacement therapy (RRT), and cerebrovascular accidents (CVAs). We systematically searched MEDLINE, Scopus, and Cochrane CENTRAL from inception through February 2025, excluding overlapping registry-based analyses. The DerSimonian-Laird effects model was applied to compute pooled odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was assessed using a visual funnel plot and the Egger's and Begg's tests. A leave-one-out sensitivity analysis was conducted to evaluate the robustness of the findings. All analyses were conducted in R statistical software (v4.3.2, R Foundation for Statistical Computing, Vienna, Austria), using the meta, metafor, and dmetar packages. Fifteen studies were included (N = 2,913). Patients receiving peripheral ECMO were slightly younger (54.8 ± 14.3 vs. 57.0 ± 13.7 years) and more often male (72% vs. 64%). Peripheral cannulation was associated with a lower risk of major bleeding (risk ratio (RR) 0.55, 95% CI 0.43-0.70), but a higher risk of limb ischemia (RR 1.43, 95% CI 1.17-1.75). No significant differences were observed for infection (RR 0.88, 95% CI 0.39-2.01), RRT (RR 1.17, 95% CI 0.66-2.08), or CVA (RR 1.19, 95% CI 0.78-1.83). Sensitivity analyses, using a leave-one-out approach, confirmed the robustness of the findings, yielding nearly identical pooled estimates and indicating that no single study disproportionately influenced the results. Peripheral venoarterial ECMO (VA-ECMO) cannulation is associated with a significantly lower risk of bleeding, but a higher risk of limb ischemia, compared with central access, with no significant differences observed in infection, RRT, or CVAs. Therefore, the choice between peripheral and central access should be individualized, based on patient-specific risk profiles, particularly balancing bleeding risk against ischemic risk.