Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has become an essential life-saving therapy for patients with refractory cardiogenic shock, cardiac arrest, and severe cardiopulmonary failure. Despite its expanding use and technological advancements, V-A ECMO is associated with significant complications, among which limb ischaemia remains one of the most devastating. The systematic review and meta-analysis by Guo et al., published in Nursing in Critical Care in 2026, provides one of the most comprehensive evaluations to date of the incidence and risk factors of limb ischaemia in adult patients supported with V-A ECMO .
The authors conducted a rigorous literature search across five major databases—PubMed, Web of Science, Embase, Cochrane Library, and Scopus—from inception through June 2025. Following PRISMA guidelines and PROSPERO registration, 17 observational studies encompassing 2,812 adult patients were included. Most studies were cohort designs, geographically diverse, and predominantly focused on peripherally cannulated V-A ECMO, reflecting contemporary clinical practice. Methodological quality was generally high, with Newcastle–Ottawa Scale scores ranging from 6 to 9.
The pooled incidence of limb ischaemia across all studies was 16.9%, although reported rates varied widely from 5.7% to 33.1%. This heterogeneity was substantial, highlighting differences in patient populations, cannulation techniques, monitoring strategies, and diagnostic criteria. Subgroup analyses suggested that no single procedural factor—such as distal perfusion cannula (DPC) use, cannulation approach, or arterial cannula size—fully explained this variability. Instead, the findings emphasize that limb ischaemia arises from a complex interaction of patient-specific and procedural factors rather than a single modifiable element.
A major strength of this analysis lies in its evaluation of risk factors. Peripheral arterial disease (PAD) emerged as a strong predictor of limb ischaemia, with an odds ratio exceeding six. Although this association showed statistical fragility due to limited contributing studies, it remains clinically plausible. Patients with PAD have compromised vascular reserve and reduced collateral circulation, making them particularly vulnerable to flow obstruction caused by large-bore arterial cannulas. This finding reinforces the importance of pre-procedural vascular assessment and heightened vigilance in patients with known vascular disease.
Unsuccessful percutaneous cannulation was identified as a consistent and clinically actionable risk factor, nearly quadrupling the risk of limb ischaemia. Mechanistically, repeated puncture attempts may cause endothelial injury, arterial spasm, or local thrombosis, all of which can impair distal perfusion. From a clinical standpoint, this underscores the importance of ultrasound-guided cannulation, early recognition of difficult access, and timely transition to surgical approaches or adjunctive perfusion strategies when necessary.
Interestingly, shorter patient height was also associated with an increased risk of limb ischaemia. While the absolute difference was modest, height likely serves as a surrogate marker for smaller femoral artery diameter and cannula-to-vessel mismatch. In smaller-stature patients, standard arterial cannulas may occupy a disproportionately large portion of the arterial lumen, increasing the risk of distal hypoperfusion. This finding supports a more individualized cannulation strategy, incorporating vessel diameter assessment rather than relying solely on standardized cannula sizes.
The study also explored numerous other potential risk factors—including age, sex, diabetes, cannula size, ECMO duration, and vasoactive medication use—but none showed a consistent association with limb ischaemia in pooled analyses. The authors appropriately caution that these null findings may reflect limited statistical power and heterogeneity rather than true absence of effect.
Beyond numerical estimates, this review has important implications for clinical practice. The authors argue convincingly for an integrated, multi-component prevention bundle rather than reliance on any single intervention. Such a bundle would include pre-procedural risk stratification, meticulous cannulation technique, continuous limb perfusion monitoring using Doppler ultrasound or near-infrared spectroscopy, and rapid, protocol-driven responses to early signs of ischaemia. The analysis also highlights the urgent need for standardized definitions and reporting of limb ischaemia to improve comparability across studies.
In conclusion, this systematic review and meta-analysis provides robust, practice-relevant evidence that limb ischaemia affects approximately one in six adults receiving V-A ECMO. By identifying PAD, unsuccessful percutaneous cannulation, and shorter stature as key risk factors, it offers clinicians concrete targets for prevention and early intervention. While further high-quality prospective studies are needed, this work represents an important step toward improving vascular outcomes and overall survival in this high-risk population .
