Room air was used as a radiographic contrast (Rotenberg 1914) prior to carbon dioxide (CO2) (Rosenstein 1921). Intravascular contrast was first used in 1924 as liquid (Brooks 1924). CO2 was studied in the arteries and veins of human patients, first via needle injection (Barrera 1956) and then via catheter delivery.
With the development of digital subtraction angiography (DSA), CO2 angiography has became a useful diagnostic test, particularly in situations where the patient is hypersensitive to iodinated contrast material or those who have compromised renal function. As a result of high-resolution DSA and more reliable gas delivery systems, CO2 angiography is now commonly used for vascular imaging and endovascular procedures.
Since CO2 angiography is not associated with allergic reactions or nephrotoxicity, it is commonly used as a contrast agent for aortography, outflow assessment, visceral angiography, and renal arteriography. This contrast agent is most commonly used:
CO2 is also used to guide vascular interventions, transcatheter embolization, and endovascular abdominal aortic aneurysm repair.
The main benefits of using CO2 for angiography are that CO2 has no adverse effect on the kidneys or the immune system, and it is the least expensive contrast medium.
CO2 can be used for a variety of procedures:
Wedged portal venography
Given its lower viscosity, CO2 is less likely than a fluid contrast to cause hepatic capsular rupture on a physiologic level, but no prospective trial has evaluated whether there is a statistical difference between the 2 in clinical use.
As with liquid contrast, CO2 raises pulmonary artery pressure and can exacerbate pulmonary hypertension. It is important to check the pulmonary arteries for the accumulation of gas and dissipation within 30 to 45 seconds.
CO2 should not be combined with nitrous oxide sedation because N2 mixes with CO2 and reduces the solubility of CO2.
CO2 arteriography should not be used above the diaphragm to avoid the possibility of causing a cerebral air embolism. There are 2 mechanisms for this to occur:
It is therefore prudent to have the patient in Trendelenburg position whenever not working deep in the mesenteric system.
Capnography (ETCO2) provides a way to monitor both ventilatory and intravascular CO2 in real time.
There is only 1 FDA-approved medical CO2 delivery system. It holds 10,000 mL of CO2, which is enough to use with hundreds of patients. The same manufacturer sells a stopcock system (also called a K-valve, because of its shape). This apparatus has:
Techniques that derive CO2 from large compressed CO2 cylinders have been used for decades but are not FDA-approved). Similar to a medical O2 cylinder, a medical grade CO2 cylinder has a metal diaphragm to keep the gas inside pure, a release valve, and a pressure gauge and pressure regulator. Single cylinders for purchase are typically sold in quantities of pounds of compressed CO2 and contain millions of mL of the CO2 set to around 18 PSI. Use of such CO2 cylinders requires a "homemade" simulation of the K valve system of the AngiAssist. Whatever technique is chosen must allow passive unidirectional flow (via a series of valves) of CO2 from the cylinder into the syringes, tubing, and/or reservoir bags. This process purges room air from the system and allows CO2 to expand until it equalizes with room atmospheric pressure. The entry and exit points of the system are then sealed until the physician is ready to connect the system to a catheter.
CO2 injection systems can be used in conjunction with
CO2 System to Catheter Hook Up
The fluid (blood/saline) in the angiographic catheter must be purged to prevent vessel dissection from explosive delivery of fluid during CO2 angiography. It is performed in a manner similar to hookup of a catheter to other angiographic contrast. One technique, the stopcock and waste syringe technique is as follows:
If the injection is performed by hand power, a large syringe is less likely than a small syringe to result in CO2 compression in the syringe followed by explosive delivery into the artery or organ.
An end-hole catheter yielded the best results, even in the aorta, IVC, and pulmonary arteries (where pigtail catheters are traditionally used for liquid contrast).
As with fluid contrast, the injection rate depends on the caliber and size of the vessel accepting the bolus and the size of the downstream vascular bed. The following volumes are ranges for amounts that are "usually" sufficient.
Abdominal aortogram/inferior vena cavogram
Aortic branches (celiac, superior mesenteric, renal arteries), common iliac arteries and veins
Wedged portal venography via the superior mesenteric artery
Common femoral arteries, second order arteries off the aorta, vessels requiring the use of a microcatheter, other veins, wedged venography (in the liver or spleen)
Proximal arteries can be imaged by refluxing CO2 from a more peripheral catheter location. Digital subtraction angiography (DSA) should be used for CO2 imaging. Veins should be injected more gently than arteries.
In an animal model, (Cho 2007) concluded that a single CO2 dose up to 1.6 mL/kg resulted in no changes in cardiopulmonary parameters. This amounts to 112 mL for a 70-Kg person, which is more than necessary for any clinical scenario.
Time Between Injections
CO2 tends to dissolve within a vessel in 30 seconds to 60 seconds. If being cautious, injections should be performed at least 2 minutes apart. For mesenteric and advanced disease peripheral artery imaging, at least 3 minutes should be considered or longer if there are symptoms. Continued visualization of CO2 should be suspected to indicate a trapped bubble and/or room air contamination. Delayed absorption may also occur in persons with COPD (who have a high baseline CO2 level).
Maintaining Image Quality
The following techniques can optimize CO2 digital subtraction angiography:
The most feared complication for intravascular use is air embolism, which can result in stroke, myocardial infarction, paralysis, amputation, or death, although this risk across all patients is less than 1%. A large amount of CO2 trapped in the pulmonary artery or right side of the heart (only of concern during venography) obstructs venous return resulting in bradycardia and hypotension. The patient should be rotated into a left lateral decubitus position if this happens to attempt to separate the CO2 into a gas layer floating "on top of" and no longer interfering with the flow of the liquid and solid components of blood. Large gas bubbles full of CO2 can remain "trapped" in the heart and/or a relatively reduced distribution of right pulmonary arterial tree until such time as their component molecules entirely dissolve into the bloodstream.
In an animal model, CO2 was injected into the coronary arteries without adverse outcome, and laboratory physiology experimentation suggests CO2 can be delivered via catheter to the coronary arteries without reflux into the cerebral circulation (Corazza 2018), but there have been no case reports of use in the coronary system in humans.
Some people experience side effects of paresthesia, tenesmus, or nausea. Normally, nausea is only encountered when high flow rates are used for angiography. There have been no reports of CO2 poisoning that presents as hypotension and hypoventilation.
Abdominal pain during mesenteric arteriography usually can be handled by rotating the patient from side to side and massaging the abdomen. However, it may signal the presence of a vapor lock. This phenomenon is when gas, which may also include endogenous nitrogen and oxygen, becomes trapped intraarterially due to having a diffusion constant the prevents its dissolving in blood while simultaneously having a high enough partial pressure relative to blood that no blood can be pumped through the gas into the capillaries. The result if not treated is mesenteric infarction. This is reported most commonly in the scenario of a large amount of CO2 collecting in an abdominal aortic aneurysm sac and then migrating into a mesenteric branch. First-line treatment involves attempting to dislodge the gas bubble mechanically via massage, patient rotation, and/or catheter aspiration.
Additional management strategies for CO2 adverse events are discussed elsewhere.
CO2 floats on the gravity-nondependent surface of blood that it does not displace entirely; abnormalities of the dependent portions of vessels may be missed. Air-fluid levels of significance in practice only occur in the aorta, the IVC, and their first order branches.
Arteries that assume a posterior course, such as lumbar and some renal arteries, may require positioning the patient more decubitus to fill.
CO2 can cause an underestimation or overstimulation of vessel caliber compared with liquid contrast or IVUS and have greater inter-observer variability in determining vessel caliber. CO2 has a lower accuracy for characterizing stenoses than liquid contrast. For example, in 27 lower extremities of adult men, CO2 opacified 86.2% (188/195) of arteries of concern and depicted stenosis adequately in 84.5% (191/226) of arterial segments. Infrapopliteal arteries were even less adequately visualized.
As CO2 passes through vascular bifurcations, the bolus dissipates and can simulate a stenosis. If there is a physiologic shunt, then CO2 injection can mimic a fistula in the absence of an anatomic fistula needing mechanical correction.
Given the somewhat inferior appearance of CO2 to liquid contrast, patients should consent that a small volume of iso-osmolar contrast (such as 10 to 20 mL) may still be used for increasing the sensitivity of detecting stenoses or confirming equivocal findings.
CO2's lower viscosity compared with liquid contrast can allow it to more easily escape a vessel and more rapidly disperse along a slow flow system (Hawkins 1997). This can make CO2 more sensitive for detecting:
Multiple reports described the detection of gastrointestinal tract bleeding  and fistula when liquid contrast did not detect the finding.
CO2 angiography is used by a minority of angiographers and at a minority of institutions, even though it can offer advantages in diagnostic accuracy and patient outcomes in some settings. Improving health care practitioner team understanding of how to promptly evaluate and treat patients using digital subtraction carbon dioxide angiography will lead to better patient outcomes. [Level V]
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