Carbon dioxide as a promising alternative to iodinated contrast media for lower extremity endovascular procedures (Review)

Carbon dioxide (CO2) angiography has emerged as an alternative contrast agent for arterial endovascular procedures, particularly in patients at increased risk of complications from iodinated contrast media (ICM). The present review evaluates the clinical circumstances in which carbon dioxide (CO2) angiography can reduce the use of iodinated contrast media (ICM) during arterial endovascular procedures, with particular attention to renal‑risk reduction, image quality, anatomical limitations, and procedure‑related complications. A narrative literature review was performed using PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and CENTRAL. Search terms included carbon dioxide angiography, CO2 contrast, ICM, peripheral artery disease, endovascular intervention, chronic kidney disease (CKD), contrast‑associated acute kidney injury (AKI), digital subtraction angiography, and digital variance angiography. Peer‑reviewed clinical studies, systematic reviews, technical reports, and guideline documents relevant to vascular applications of CO2 were included. Additional PubMed‑indexed studies were incorporated to strengthen the discussion of kidney‑risk terminology, lower‑extremity outcomes, and contemporary evidence. The most consistent evidence supports CO2 angiography as an ICM‑sparing strategy for iliac and lower extremity interventions, especially in patients with CKD, previous post‑contrast AKI, or ICM hypersensitivity. CO2 reduces iodine exposure and may contribute to reducing contrast‑associated renal complications while preserving procedural success in selected lesions. However, image quality is influenced by buoyancy, catheter position, patient positioning, vascular orientation, and post‑processing. Evidence for abdominal aortic and transplant renal artery applications is less uniform, and mesenteric use is limited by clinically important ischemic complications. Arterial use above the diaphragm remains contraindicated due to the risk of cerebral or coronary gas embolism. CO2 angiography should not be regarded as a universal substitute for ICM. Its strongest role is as a renal‑sparing alternative or adjunct in infra‑diaphragmatic peripheral arterial interventions, particularly in lower extremity disease. Safe implementation requires appropriate patient selection, closed or automated delivery systems, standardized injection protocols, pain management, and awareness of anatomical contraindications.