Carbon Dioxide Angiography

Overview

Carbon dioxide (CO₂) gas was used as a contrast agent in the venous circulation in the 1950s and 1960s to delineate the right heart for evaluation of suspected pericardial effusion. This imaging developed from animal and clinical studies, which demonstrated that CO₂ use was safe and well tolerated with peripheral venous injections.

In the 1970s, CO₂ was used as an intra-arterial contrast agent. With the advent of digital subtraction angiography (DSA) in 1980, CO₂ angiography became a useful diagnostic tool, particularly in patients who were hypersensitive to iodinated contrast material or whose renal function was compromised. Now, with the availability of high-resolution DSA and a reliable gas delivery system, CO₂ angiography has become widely used for vascular imaging and endovascular procedures.

CO₂ is used as an alternative to iodinated contrast media in patients who are at high risk for contrast-induced nephropathy and in cases in which a patient has a known allergy to contrast media.

Because the use of CO₂ is not associated with nephrotoxicity or allergic reactions, it is increasingly being used as a contrast agent for aortography, as well as for outflow assessment, renal arteriography, and visceral angiography. The gas is the preferred contrast agent for central venography of the upper extremity; for wedged hepatic venography to visualize the portal venous system before transjugular intrahepatic portosystemic shunt (TIPS); for fine-needle TIPS procedures and splenoportography 

CO₂ is used to guide various vascular interventions, including angioplasty and stent placement, transcatheter embolization, vena cava filter placement and endovascular abdominal aortic aneurysm (AAA) repair.

CO₂ should not be used as an arterial contrast agent in sites above the diaphragm because of the risk of gas embolism of the spinal, coronary, and cerebral arteries. The inadvertent entry of CO₂ into the cerebrovascular circulation during angiography can cause fatal brain injury.
 CO₂ may be delivered by the hand-held syringe method, by the plastic bag system, or by the CO₂mmander and AngiAssist. These delivery systems are safe if used correctly. Because air is poorly soluble, air contamination must be prevented during the delivery of CO₂. Thorough understanding of the physical properties of CO₂ and facile catheterization technique are essential in obtaining optimal CO₂ imaging for both diagnosis and intervention.

CO₂ should not be combined with nitrous oxide for sedation because when nitrous oxide mixes with CO₂, the solubility of CO₂ in the blood is reduced, preventing its excretion.

Chemical and physical properties of CO2

When CO₂ is injected into the blood, it is combined with water to produce carbonic acid. It becomes bicarbonate (HCO₃^–) in the blood stream; bicarbonate reverts to CO₂ before being expelled out of capillaries into the lung. Carbonic anhydrase catalyzes the conversion of CO₂ to bicarbonate and protons. CO₂ is eliminated by the lungs in a single pass. However, CO₂ bubbles that were injected into the venous system may enter the systemic circulation via the patent foramen ovale or intracardiac septal defects.

CO₂ is a colorless and odorless gas, and it cannot be visually distinguished from air. The incorrect application of technique may result in air contamination, which may cause serious complications. A thorough understanding of the unique physical properties of CO₂ is necessary for the safe and effective performance of CO₂ angiography and CO₂-guided vascular interventions. CO₂ is approximately 20 times more soluble than oxygen. When injected into a vessel, CO₂ bubbles completely dissolve within 2-3 minutes; however, if the gas is trapped in a large abdominal aneurysm, it may persist, allowing gas exchange between the CO₂ and nitrogen in the blood. This exchange may result in colonic ischemia, as a result of occlusion of the inferior mesenteric artery. Two to three minutes should elapse between injections of CO₂ to prevent the localized accumulation of gas bubbles, which may produce a significant gas embolism, particularly in the pulmonary artery.

CO₂ is compressible during injection; it expands in the vessel as it exits the catheter. Clearing the fluid of the catheter by using 3-5 cc of CO₂ before injection reduces the explosive delivery. The explosive delivery is unlikely to cause vascular damage, but it may contribute to discomfort during the injection. The low viscosity and compressibility of the gas accounts for the greater sensitivity of CO₂ as a contrast agent in detecting the source of bleeding (gastrointestinal tract and traumatic bleeding in the liver, spleen and pelvis), as compared to iodinated contrast material.

CO₂ is lighter than blood plasma; therefore, it floats above the blood. When injected into a large vessel, such as the aorta or inferior vena cava, CO₂ bubbles flow along the anterior part of the vessel, with incomplete blood displacement along the posterior portion. Because of their anterior point of origin, the celiac and superior mesenteric arteries fill well with small volumes (< 15 cc) of CO₂. If gas fails to fill the renal artery originating from the posterolateral aspect of the aorta, the patient must be rotated so that the side of the renal artery to be visualized is elevated above the level of the injection site. If the renal artery remains unfilled, catheterization of the artery and selective injection are indicated.

The buoyancy of the gas is not a problem when the vessel to be imaged is smaller than 10 mm in diameter, because the gas bubbles tend to displace the blood in more than 80% of the lumen. Elevation of the lower extremity to 15-20° in conjunction with the intra-arterial injection of 100-200 µg of nitroglycerin enhances gas flow and filling of the distal arteries in the lower extremity.

CO₂ is approximately 400 times less viscous than iodinated contrast medium. The low viscosity permits manual gas injection with small-bore catheters and between the catheter and guide wire. Doses of CO₂ required for aortic imaging may be manually injected by using a 4-Fr or 5-Fr end-hole diagnostic catheter. The low viscosity accounts for better filling of collateral vessels for both arterial and venous occlusive diseases and for portal vein visualization through the hepatic sinusoids after wedged hepatic or liver parenchymal injection with CO₂.

Iodinated contrast medium mixes with blood when injected into a vessel and becomes diluted, making it less dense as it travels through collateral vessels. By contrast, CO₂ does not mix with blood, and therefore, it does not become diluted by collateral flow.

Advantages of carbon dioxide

CO₂ is less dense than iodinated contrast medium, thus requiring digital subtraction angiography with good contrast resolution for gas imaging. The overall quality of CO₂ vascular images is slightly less than that obtained with contrast medium. Usually, multiple hand injections are required, and the radiation exposure to the operator and patient may be increased. However, CO₂ has several notable advantages, as compared to iodinated contrast medium, as noted below.

CO₂ causes no allergic reaction. Because CO₂ is a natural by-product, it cannot cause a hypersensitivity reaction. Therefore, CO₂ is an ideal alternative to iodinated contrast medium for patients who have a history of allergic reactions. No steroid preparation is needed when CO₂ is used.

CO₂ causes no renal toxicity. Experimental and clinical findings indicate that the selective injection of CO₂ into the aorta or into the renal artery is safe and causes no renal injury, even in patients with diabetes or compromised renal function. Therefore, the gas is the preferred contrast agent for renal artery angioplasty and stent placement.

CO₂ causes no hepatic toxicity. The authors have personally used CO₂ as a contrast agent for celiac, splenic, superior mesenteric, and hepatic arteriograms for patients with a variety of disorders. No injuries to the hepatic parenchyma have occurred after the injection of CO₂.

Unlimited amounts of CO₂ may be used for vascular imaging because the gas is effectively eliminated by means of respiration. However, the operator should allow sufficient time for its clearance. A minimum of 2 minutes is needed for the first CO₂ dose to completely dissolve before another dose is injected. CO₂ is particularly useful for patients with compromised cardiac and renal function who are undergoing complex vascular interventions.

Because of the low viscosity, CO₂ angiography is more sensitive in detecting gastrointestinal and traumatic pelvic bleeding than iodinated contast medium. CO₂ can be injected through a small catheter, such as 3-Fr microcatheter, for diagnostic angiography and CO₂-guided endovascular interventions. When injected into the iliac or femoral artery, CO₂ can visualize both the proximal and distal vessels. For example, CO2 injected into the proximal femoral or external iliac artery will reflux centrally filling the aorta and the contralateral iliac and femoral artery. CO₂ reflux angiography with a gas injection into a segmental renal artery is used to fill the proximal renal artery originating from the posterolateral aspect of the aorta.

Disadvantages of carbon dioxide

After injection, CO₂ floats on the surface of blood, so that abnormalities of the dependent portions of vessels may be missed. Also, imaging of arteries such as the lumbar and some renal arteries, which follow a posterior course, may only fill with the patient in a more decubitus position.

CO₂ can cause an underestimation or an overstimulation of vessel caliber and has greater interobserver variability in determining vessel caliber when compared with liquid contrast or intravascular ultrasound. CO₂ also has a lower accuracy rate for characterizing stenoses than does liquid contrast.

CO₂ passing through a vascular bifurcation dissipates and can simulate a stenosis. In cases of the presence of  a physiologic shunt, CO₂ can mimic an anatomic fistula.