Room air was used as a radiographic contrast (Rotenberg 1914) prior to the use of carbon dioxide (CO2) (Rosenstein 1921). The first intravascular contrast to be used in humans in 1924 was a liquid (Brooks 1924). Decades later, 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) and FDA-approved CO2 delivery systems, CO2 angiography has became a useful alternative to more commonly used iodinated contrast, particularly in situations where the patient is hypersensitive to iodinated contrast or has compromised renal function.
CO2 angiography does have limitations and risks that must be understood prior to its use by novice angiographers.
The main benefits of using CO2 for angiography are that CO2 has no adverse effects on the kidneys or the immune system and that it is the least expensive contrast medium.
CO2 can be used for a variety of procedures:
Wedged portal venography
Given its lower viscosity, when used properly CO2 is theortically less likely than fluid contrast to cause injury to the tissues into which it is infused, such as hepatic capsular rupture in wedged hepatic venography, but no prospective trial has evaluated whether there is a significant clinical difference.
CO2 should not be combined with nitrous oxide sedation because N2 mixes with CO2 and reduces the solubility of CO2 in blood preventing its excretion.
CO2 arteriography should not be used above the diaphragm to avoid the possibility of causing a cerebral air embolism with associated stroke or death. There are two mechanisms by which cerebral air embolism occur:
It is therefore prudent to have the patient in slight Trendelenburg position when possible.
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. Carbon dioxide coronary angiography: A mechanical feasibility study with a cardiovascular simulator. AIP Advances 8, 015225), but there have been no case reports of use in the coronary system in humans.
As with liquid contrast, CO2 raises pressure in intravascular beds and can exacerbate local vascular hypertension, such as in the pulmonary arteries. It is thus still important to be cautious of contrast over-administration in persons who have locoregional vascular hypertension, such as pulmonary artery hypertension, before overdistending the vascular bed. Knowing a patient's risk for this can be determined by measuring local vascular pressure with a pressure gauge. In patients who are believed to be susceptible to pressure exacerbation from contrast injection, the arteries (e.g. pulmonary arteries) should be examined regularly on fluoroscopy for dissipation of injected gas, which normally occurs within 30 to 45 seconds after contrast administration.
Capnography (ETCO2) provides a way to monitor both ventilatory and intravascular CO2 retention in real time. Capnography monitors and tubing should be used in general during conscious sedation cases according to national guidelines.
Whatever equipment setup is chosen must allow passive unidirectional flow (via a series of valves) of CO2 from a high pressure cylinder into a series of syringes, tubing, and/or reservoir bags. This process must allow CO2 to expand until it equalizes with room atmospheric pressure while also purging room air from the system, as room air injected into the patient will not dissolve quickly in blood and will potentially form a clinically significant air embolus.
There is presently only one FDA-approved medical CO2 delivery system, which is comprised of two main components: a CO2 high pressure reservoir/delivery device called the AngiAssist and a low pressure valve/stopcock system called the K-valve. The AngiAssist CO2 reservoir holds 10,000 mL of CO2, which is enough to distribute over hundreds of procedures. The valve/stopcock system, which the manufacturer calls a K-valve because of its resemblance to that letter, has:
Large (e.g. >2 feet tall) medical grade CO2 cylinders have been used for decades as a source of CO2 for angiography 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 the cylinder pure, a release valve, and a pressure gauge and pressure regulator. Single cylinders for medical use are typically sold in quantities of pounds of compressed CO2 and contain millions of milliliters of CO2 set to around 18 PSI. Use of such CO2 cylinders requires a separately "home made" or purchased simulation of the K valve system via a network of tubes, bags, syringes, and stopcocks in order to depressurize the CO2 while keeping it pure on its way into the patient. The entry and exit points of the system must be sealed until the physician is ready to connect the system to a catheter.
CO2 injection systems can also be used in conjunction with
An angiographic technologist who is trained in the setup and safe use of the CO2 delivery apparatus is crucial for maintaining patient safety.
Fluid (blood/saline) in the angiographic catheter must be purged to prevent vessel dissection from explosive delivery of fluid during CO2 angiography. One technique, the "stopcock and waste syringe technique," is as follows:
If the injection is performed by hand power, then using a larger syringe (20-30 cc) is less likely to result in CO2 compression in the syringe followed by explosive delivery into the artery or organ than using a 10 cc syringe as more typically used for hand injecting liquid contrast.
An end-hole catheter for CO2 injection yields the best results, even in the aorta, IVC, and pulmonary arteries where pigtail catheters are traditionally used performing flush arteriograms with liquid contrast.
As with fluid contrast, CO2 injection rates depend 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.
Veins should be injected more gently than arteries.
In an animal model (editors Cho K, Hawkins I. 2007. Carbon Dioxide Angiography: Principles, Techniques, and Practices), a single CO2 dose up to 1.6 mL/kg resulted in no changes in cardiopulmonary parameters. This corresponds 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 practicing caution, injections should be performed at least 2 minutes apart. For mesenteric and advanced disease peripheral artery imaging, the interval between injections should be at least 3 minutes in asymptomatic patients and longer if there are symptoms of mesenteric flow disturbance, such as pain. Continued visualization of CO2 beyond a 3 minute interval should be suspected to indicate a trapped CO2 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 when managed by experienced physicians 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 suffering this phenomenon should be rotated into a left lateral decubitus position in an 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 be allowed to remain "trapped" in the heart and/or a relatively reduced distribution of right pulmonary arterial tree. Within a relatively short time depending on the size of the bubbles, the gas molecules will entirely dissolve into the bloodstream.
Some people experience side effects of paresthesia, tenesmus, or nausea. Normally, nausea is only encountered when high flow rates are used for angiography.
Abdominal pain during mesenteric arteriography usually can be handled by rotating the patient from side to side and massaging the abdomen. However, persistent abdominal pain 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 the gas 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 event 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.
There have been no reports of CO2 poisoning; CO2 poisoining from non-angiographic sources presents as hypotension and hypoventilation.
CO2 floats on the gravity-nondependent surface of blood; therefore, 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.
Imaging of arteries that assume a posterior course, such as lumbar and some renal arteries, may only fill after positioning the patient more decubitus than supine.
Compared with liquid contrast or intravascular ultrasound (IVUS), CO2 can cause an underestimation or overstimulation of vessel caliber and has greater inter-observer variability in determining vessel caliber. CO2 also has a lower accuracy for characterizing stenoses than liquid contrast. For example, in 27 lower extremities of adult men, CO2 opacified only 86% (188/195) of arteries of concern and depicted stenosis adequately in only 85% (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 an anatomic fistula in the absence of an anatomic fistula needing mechanical interruption.
Given the somewhat inferior appearance of CO2 to liquid contrast, at the time of patient procedural consent the physician should discuss with the patient whether the patient will agree to allow the physician to inject a small volume of iso-osmolar iodinated contrast (such as 10 to 20 mL) in order to detect 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. This can make CO2 more sensitive than liquid contrast for detecting a/an:
Gastrointestinal tract bleeding  and fistulae have been observed with CO2 in circumstances 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 practitioners understanding of advantages of CO2 angiography can enable practitioners to select CO2 contrast over conventional contrast in appropriate situations that may lead to better patient outcomes. [Level V]
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