For the general practitioner
When your patient needs angiography: what to know and how to refer them
The GP is often the first to receive the patient's request for clarification — and the first who can make a difference, referring them to facilities that use safer techniques for renal function.
Pre-procedural assessment
Who is really at risk of contrast-induced nephropathy?
Contrast-induced nephropathy (CI-AKI) remains one of the most frequent iatrogenic causes of acute kidney injury in hospital. Identifying at-risk patients before the procedure is the most effective time to prevent it.
1–5%
of patients with healthy kidneys develop CI-AKI
25–30%
of patients with CKD stage 3–4 + diabetes
40–50%
of patients with multiple high-risk factors
+3.5 days
average additional length of stay for patients with CI-AKI
Risk stratification by GFR
| GFR (ml/min/1.73m²) | CKD stage | CI-AKI risk | Recommendation |
|---|---|---|---|
| > 60 | 1–2 | Low | Iodinated contrast with standard precautions (hydration) |
| 45–60 | 3a | Moderate | Consider CO₂ if available; IV hydration recommended |
| 30–45 | 3b | High | Prefer CO₂; if iodine is used, minimum effective dose |
| < 30 | 4–5 | Very high | CO₂ recommended; iodine only if not replaceable |
| Dialysis | 5D | Renal: absent | CO₂ preferable to avoid systemic complications |
Additional risk factors
- ⚠Diabetes mellitus — even with GFR > 60, significantly increases risk
- ⚠Peripheral artery disease — often associated with subclinical CKD
- ⚠Ongoing metformin — lactic acidosis risk; suspend 48h before if iodinated contrast is used
- ⚠NSAIDs and diuretics — reduce renal perfusion
- ⚠Dehydration — amplifies nephrotoxic damage
- ⚠Heart failure — reduces baseline renal flow
- ⚠Age > 70 years — renal function physiologically declines with age
⚠ The highest-risk triad: diabetes + CKD stage 3b–4 + peripheral artery disease. In these patients, iodinated contrast media should be avoided whenever a viable alternative such as CO₂ exists.
📚 Sources and scientific references
Selection of recent clinical studies and systematic reviews on CO₂ angiography and contrast-induced nephropathy.
Renal risk from iodinated contrast media
- Mehran R, et al. A Simple Risk Score for Prediction of Contrast-Induced Nephropathy. J Am Coll Cardiol. 2004. PubMed →
- Weisbord SD, et al. Contrast-Associated Acute Kidney Injury. N Engl J Med. 2019. PubMed →
- Wittig T, et al. Acute Kidney Injury After Peripheral Interventions Using Carbon Dioxide Angiography — Risk Factors Beyond Iodinated Contrast Media. Life. 2025. PubMed →
- Uyanik SA, et al. The role of carbon dioxide angiography in reducing contrast-induced nephropathy in diabetic foot patients undergoing endovascular treatment. Turkish J Med Sci. 2025. PubMed →
CO₂ as an alternative to iodinated contrast — systematic reviews and meta-analyses
- Wawer Matos Reimer RP, et al. Safety and evidence of CO₂ as a vascular contrast agent — systematic review by the ESUR Contrast Medium Safety Committee. European Radiology. 2025. PubMed →
- Shen G, et al. CO₂ angiography offers clinical advantages over iodinated contrast in endovascular aneurysm repair: a systematic review and meta-analysis. BMC Surgery. 2025. PubMed →
- Felici L, et al. Optimizing Endovascular Aortic Repair With Carbon Dioxide: A Systematic Review Toward Zero Contrast Use. Vascular and Endovascular Surgery. 2025. PubMed →
- Spath P, et al. Systematic Review of Renal Outcomes and Procedural Efficacy of CO₂ Digital Subtraction Angiography in Endovascular Aortic Repair. EJVES Vascular Forum. 2026. PubMed →
Prospective clinical studies — Zero Iodine Contrast
- Chisci E, et al. Feasibility and Safety of Using Carbon Dioxide Exclusively in Regular Endovascular Aortic Aneurysm Repair: Results of a Multicentre, Prospective, Zero Iodine Contrast EVAR Study. Eur J Vasc Endovasc Surg. 2025. PubMed →
- Falso R, et al. Total Iodine Contrast-Free Protocol in Complex Endovascular Aneurysm Repair. Journal of Endovascular Therapy. 2025. PubMed →
- Allievi S, et al. Towards Contrast Free EVAR: CO₂ Automated Angiography in Chronic Kidney Disease. Eur J Vasc Endovasc Surg. 2023. PubMed →
- Busutti M, et al. Renal Benefits of CO₂ as a Contrast Media for EVAR Procedures: New Perspectives on 1 Year Outcomes. Journal of Endovascular Therapy. 2023. PubMed →
Ongoing randomised trials
- Saratzis A, et al. Preventing kidney injury using carbon dioxide (KID trial): trial protocol for a multicentre randomised controlled trial. BMJ Open. 2025. PubMed →
Clinical indications
When and how to indicate CO₂ in the clinical request
The GP can make a difference in the diagnostic chain by explicitly indicating in the clinical request the need for an alternative technique to iodinated contrast media.
📋 How to write the clinical request
- Indicate the renal condition: "Patient with CKD stage 3b (GFR: ___ ml/min) and type 2 diabetes mellitus."
- Report the risk: "Relative contraindication to iodinated contrast media due to high CI-AKI risk."
- Request the alternative: "CO₂ angiography is requested as an alternative contrast medium (if technically applicable for the requested anatomical site)."
- Attach the data: Recent creatinine and GFR, medication list (metformin, NSAIDs, diuretics), any history of reactions to contrast media.
Where CO₂ is indicated and where it is not
| Anatomical site | CO₂ indicated? | Notes |
|---|---|---|
| Lower limb arteries | ✓ First choice | Main indication, excellent image quality |
| Abdominal aorta / EVAR | ✓ Indicated | Widely used in zero-contrast protocols |
| Renal arteries | ✓ Indicated | Particularly useful precisely in nephropathic patients |
| Visceral arteries | ✓ With caution | Growing use, depends on centre experience |
| Dialysis fistulas | ✓ Indicated | Excellent alternative for dialysis patients |
| Coronary arteries | ✗ Not indicated | Risk of cerebral gas embolism above the diaphragm |
| Cerebral / carotid vessels | ✗ Not indicated | Contraindicated above the diaphragm |
Practical management
What to do before and after the procedure
Pre-procedure — checklist for the GP
- ✓Request updated creatinine and GFR (within 3 months, preferably within 30 days)
- ✓Suspend metformin 48h before the procedure (if iodinated contrast is used); resume after 48h with stable GFR
- ✓Consider temporary suspension of NSAIDs and diuretics in agreement with the specialist
- ✓Ensure the patient is adequately hydrated on the day of the exam
- ✓Collect allergy history: previous reactions to contrast media, iodine allergies
- ✓Indicate the renal risk profile in the clinical request and explicitly request CO₂ if indicated
Post-procedure — monitoring
- ✓Request follow-up creatinine and GFR at 24–48h after the procedure (if iodinated contrast was used)
- ✓If creatinine increases > 0.3 mg/dL or > 50% from baseline: nephrology consultation
- ✓Resume metformin only after confirming stable renal function
- ✓Monitor urine output in the 24h following the exam
Communicating with the patient
How to explain CO₂ to a worried patient
The patient's most common concern is that CO₂ is "experimental" or "dangerous". Some useful phrases to reassure them:
"But isn't gas in the veins dangerous?"
CO₂ is a gas naturally produced by the body in quantities enormously greater than those used in angiography. It is rapidly eliminated through the lungs simply by breathing. With modern automated injection systems, the procedure is safe and controlled. Over 30 years of clinical use and robust scientific literature confirm its safety.
"Is this a new technique? I prefer regular contrast media"
CO₂ angiography has been used in medicine for over 30 years and is recommended by the leading international interventional radiology and vascular surgery guidelines for patients at high renal risk. It is not experimental — it is the standard of care for nephropathic patients in specialised centres.
"Will the images with gas be less clear?"
With modern automated digital injection systems, the image quality obtainable with CO₂ is clinically adequate for lower limb and aortic procedures. In some cases it can be used in combination with small doses of iodinated contrast media ("CO₂-first" technique) to further optimise quality, while still maintaining a significant reduction in nephrotoxic load.
💡 You can refer the patient to the paziente-en.html page of this site for a simple, complete explanation to read before the exam.
For the vascular surgeon and interventional radiologist
CO₂ angiography: from technique to protocol standardisation
CO₂ as a contrast medium is no longer a niche: it is the recommended standard of care for nephropathic patients and represents a clinical and reputational asset for centres that adopt it systematically.
Why systematise
The problem: contrast-induced AKI in endovascular patients
Patients arriving in the angiography suite for peripheral artery disease are often the same ones presenting the highest risk profile for CI-AKI: elderly, diabetic, with subclinical or overt CKD. It's the perfect storm.
~30%
of PAD patients have CKD stage 3 or higher
50–70%
of these also have diabetes mellitus
+40%
1-year mortality in patients who develop CI-AKI
100+
facilities in Italy already equipped with CO₂ technology
⚠ Medico-legal responsibility: in the presence of a patient with documented CKD for whom an alternative to iodinated contrast media exists (CO₂), using the latter without documenting the clinical reasons exposes the physician to risk of liability.
Operational protocol
How to structure a CO₂ protocol in your centre
Phase 1 — Patient selection
- Check pre-procedural GFR (critical threshold: < 45 ml/min → CO₂ preferred)
- Collect contrast media allergies and metformin use
- Assess anatomical site: below the diaphragm → CO₂ indicated
- Document the choice in the informed consent
Phase 2 — Injection technique
- Automated digital injection system — eliminate manual dosing; ensures precise control of volume, pressure and injection speed
- Certified medical CO₂ source (purity > 99.9%)
- Typical volumes: 20–60 ml per injection, with adequate pauses between injections to allow pulmonary clearance
- Patient positioning: Trendelenburg position to improve image quality for lower limbs
- Image acquisition: DSA (Digital Subtraction Angiography) with protocols optimised for CO₂
Phase 3 — Hybrid approach (CO₂-first)
- Perform the entire procedure with CO₂ as the primary medium
- Use iodinated contrast only for critical phases requiring maximum resolution (e.g. angioplasty in a critical area)
- Goal: reduce total iodinated contrast dose by > 70% compared to the standard protocol
- Document the total iodinated contrast dose used for each case
Absolute contraindications to CO₂
- ✗Procedures above the diaphragm (coronary, carotid, vertebral, aortic arch)
- ✗Right-to-left intracardiac or intrapulmonary shunts (risk of systemic embolism)
- ✗Severe pulmonary hypertension
Economic impact
Costs and benefits for the hospital: the value-based healthcare case
Contrast-induced nephropathy is not just a clinical problem — it is a significant economic problem for any hospital facility adopting value-based healthcare logic.
Direct cost of a CI-AKI case
- →+3–5 additional days of hospitalisation per patient who develops CI-AKI
- →Additional stay cost: €800–1,200/day in a standard ward
- →Emergency dialysis (in severe cases): €400–600 per session, often repeated
- →30-day readmissions: frequent in patients who develop post-procedural CI-AKI
- →Impact on DRGs: post-procedural complications reduce the margin on the hospitalisation
💡 Estimated savings: a centre performing 200 angiographies/year on high-risk patients, reducing CI-AKI incidence from 25% to 5% through systematic CO₂ adoption, avoids approximately 40 CI-AKI cases/year — with potential savings of €120,000–200,000 annually in avoided hospital stays alone.
The cost of CO₂ vs iodinated contrast media
The cost of medical CO₂ gas is significantly lower than that of iodinated contrast media per procedure. The main investment is in the automated injection system, which pays for itself quickly considering the costs of avoided complications.
Frequently asked clinical questions
Clinical FAQ for the specialist
Is image quality with CO₂ sufficient for complex procedures?
With modern automated digital injection systems and optimised DSA protocols, diagnostic quality is clinically adequate for the vast majority of lower limb and aortic procedures. CO₂ has different physical properties than iodinated contrast: compressible gases produce different artefacts that require adapting the acquisition technique, but do not compromise diagnosis. For the most critical phases of a procedure, it's always possible to supplement with a small dose of iodinated contrast (hybrid CO₂-first approach).
How to manage a dialysis patient who needs angiography?
In the dialysis patient, the concern for CI-AKI is already moot (the kidneys aren't functioning), but using iodinated contrast remains discouraged because it can damage residual renal function, make fluid management more difficult and, in some cases, complicate dialysis fistula management. CO₂ is the ideal choice — especially for arteriovenous fistula angiography, where it offers excellent image quality.
How to manage a case where CO₂ alone is not sufficient?
- Hybrid CO₂-first technique: use CO₂ for the entire diagnostic phase and only small doses of iodinated contrast for the critical interventional phase
- Optimise patient positioning (Trendelenburg) to improve CO₂ image quality
- Use DSA post-processing software specific to CO₂
- In truly complex cases: discuss the risk/benefit ratio with the nephrologist and document the choice
How many ml of CO₂ can be injected in total per session?
There is no standardised absolute limit, because CO₂ is rapidly eliminated through the lungs. Common clinical practice involves injections of 20–60 ml each, with 1–2 minute pauses between injections to ensure pulmonary clearance. Digital automated injection systems track volumes in real time and can set operator-configurable safety limits.
🏥 Over 100 facilities in Italy already use CO₂
Are you a physician wanting to know where to refer a patient, or a specialist wanting information about Angiodroid® systems? Write to us.
✉ Send us an email
We'll respond with information about the nearest facility or available systems in Italy
or copy the address: scrivi@angiodroid.com