Radiological Contrast Agents

From the earliest days of radiology, considerable effort has been devoted to developing compounds that if swallowed or injected would increase the radiographic contrast between various tissues and organs. Injection of air or other gases into a GI tube in the esophagus, stomach, or duodenum or into a rectal tube in the colon provides increased radiographic contrast for evaluating the gut; however, the information obtained by this technique is limited, and more opaque substances have been developed.

Any agent or compound administered to a patient to improve the visualization of an organ or tissue is called a contrast agent. Contrast agents can be classified as negative or positive. Air and other gases are negative contrast agents because they render a structure, such as the gut, more translucent. An agent that increases the radiographic opacity of an organ or tissue is a positive contrast agent. Most contrast agents used in diagnostic radiology are positive contrast agents.

An ideal radiographic contrast agent should have the following properties: (a) readily available, (b) inexpensive, (c) excellent x-ray absorption characteristics at the x-ray energies used in diagnostic radiology, (d) minimal toxicity, (e) patient acceptance, (f) chemical stability, (g) high-water solubility with low viscosity and no significant osmotic effects, and (h) the ability to be administered for selective tissue uptake and excretion.

No compound has all of these characteristics. Barium sulfate and various iodine compounds, however, produce excellent radiological contrast with low patient toxicity and relatively low cost. The use of barium and iodine compounds as radiological contrast agents is based on their radiographic appearance, distribution, and elimination from the body. Contrast media are used in very large quantities and are usually administered over a brief period of time.

Barium sulfate is a nearly ideal contrast agent for oral and rectal studies of the GI tract. It produces a metal-like density on radiological studies, is inexpensive, and when properly utilized, has minimal patient morbidity and mortality. While various water-soluble barium compounds are quite toxic, barium sulfate is an insoluble white power that is a colloidal suspension in water.

Most intravenous contrast agents used to opacify blood vessels and increase contrast in solid organs, such as the liver, are water-soluble organic iodides. Iodine absorbs x-rays effectively at many energy levels and produces opacities similar to bone density during radiographic studies. While iodine's radiographic density is somewhat less than that of barium sulfate, it is still very useful for radiographic contrast.

Early water-soluble contrast agents consisted of triiodi-nated benzoic acid salts. In solution, these salts dissociate into two particles: (a) a triiodinated anion and (b) a cation, usually sodium or methylglucamine (meglumine). These compounds, known as high-osmolar contrast medium (HOCM), have in effect three iodine atoms for every two ions in solution, a 3:2 ratio. They are often called conventional, ionic ratio 1.5 contrast agents, or triiodinated monomers and are represented by diatrizoate and iothala-mate.37 Various fixed ratios of sodium diatrizoate and meg-lumine diatrizoate are also available in proprietary products.

These water-soluble iodinated salts are administered in fairly high volumes and concentrations to achieve satisfactory radiological contrast. It is not unusual to administer as much as 100 mL or more of a 30% to 70% solution intra-venously.38 The typical concentrations used for various studies have an osmolality of 5 times or more to that of normal plasma. Administration of these HOCM agents can be associated with osmotoxic effects. Initially, water shifts rapidly from the interstitial and cellular spaces into the plasma after injection of an HOCM. This is typically accompanied by vasodilatation, local pain and warmth, a metallic taste in the mouth, and flushing. Later, there is an osmotic diuresis as these agents are excreted by the kidneys.

Various nonionic water-soluble compounds with a higher ratio of iodine content per osmotic particle have been developed. These types of agents, known as low-osmolar contrast medium or isotonic contrast media (LOCM or ICM), produce far fewer osmotic effects. Various monomers such as iohexol, iopamidol, iopramide, ioversol, and ioxilan as well as dimers such as iodipamide, iodixanol, and ioxaglate have been described.38

All of the water-soluble iodinated contrast media are clear, colorless, viscous liquids. Even though they are clear liquids, they are often called "dyes" when their administration is being explained to patients. Sodium salts are slightly less viscous than the meglumine salts, which are typically less viscous than nonionic monomers, which are typically less viscous than non-ionic dimers. Viscosity is a function of temperature and can be reduced by warming the contrast agent to body temperature prior to its administration.

Water-soluble iodinated contrast media have relatively small molecular sizes and low chemical reactivity with body fluids and tissues. Their pharmacodynamic characteristics are similar to those of extracellular tracers. They have low lipid solubility and distribute throughout extracellular spaces. They do not significantly penetrate into intracellular spaces. Special attention must be given to ensure that iodin-ated contrast agents are not administered intrathecally unless they are indicated for such use. Inadvertent intrathecal administration can cause serious outcomes such as convulsions, cerebral hemorrhage, brain edema, and death.

Water-soluble iodinated contrast agents are cleared from the body by glomerular filtration. They are neither reabsorbed nor secreted by the renal tubules. When renal function is compromised, these contrast agents are eliminated in part or totally through the liver and gut. This alternate elimination pathway occurs at a much slower rate than elimination when compared with glomerular filtration in a healthy person.

Water-soluble organic iodides are the largest group of radiological contrast agents. In addition to water-insoluble barium sulfate, there is an iodinated fatty acid derivative of poppy seed oil that is occasionally utilized in the clinic. Unsaturated fatty acids are monoiodicated or diiodinated before conversion to an ester. These substances are susceptible to light-induced decomposition, and the oily nature of the formulation excludes intravascular use.

Radiological contrast agents that are administered orally or intravascularly in large amounts infrequently report adverse effects. Nevertheless, any radiological contrast material may produce an untoward patient reaction, even sudden death.39-42

Events can occur when contrast material is aspirated or when it leaks from the GI tract. Hypertonic ionic water-soluble contrast agents are potentially dangerous if aspirated into the tracheobronchial tree. They are irritating and can cause pulmonary edema. Contrast material that leaks out of the bowel into the abdomen, pelvis, or chest is potentially quite dangerous, especially barium sulfate. Barium sulfate is insoluble, and its particulate nature means it is poorly cleared from the mediastinum, peritoneum, and retroperitoneum. Water-soluble agents, on the other hand, are rapidly absorbed from these areas almost as quickly as if they had been injected intravenously. In general, water-soluble agents that leak from the GI tract rarely cause significant problems beyond transient inflammation.

The intravenous or intra-arterial injection of iodinated contrast material can lead to a diverse assortment of contrast reactions, most of which are minor and easily treated. Minor reactions include injection pain, a feeling of general body warmth and discomfort, mild nausea and vomiting, a strong metallic taste in the mouth, and mild urticaria (hives). Minor reactions dissipate within a few minutes with patient reassurance and observation.

Intermediate or moderate reactions are those that require some form of therapy but are not life-threatening. These reactions include difficulty breathing, severe hives, severe nausea and vomiting, mild hypotension, wheezing, and other related reactions. Treatment ranges from administration of intravenous fluids to the use of intravenous diphenhy-dramine and/or corticosteroids. Epinephrine may be administered, and atropine is used if there is a vasovagal reaction with hypotension and bradycardia.

Severe reactions are those that are life-threatening. They include sudden cardiovascular collapse and death, as well as severe hypotension; severe shortness of breath, wheezing, or laryngoedema; loss of consciousness; massive hives and an-gioneurotic edema; ventricular cardiac arrhythmias; angina; and myocardial infarction. Treatment depends on the patient's signs and symptoms and includes intravenous fluids, oxygen, various drugs (including epinephrine, diphenhydramine, and atropine), and possible cardiopulmonary resuscitation (CPR).

Barium Sulfate. Commercial preparations of barium sulfate differ in their density and ability to coat the bowel wall. These characteristics are determined by the particle size of the barium suspension, its viscosity, and concentration of the contrast agent. Flavoring agents, suspending agents, and other additives may be utilized in preparing various products.

Barium sulfate preparations are given orally or rectally and are used to study the esophagus, stomach, duodenum, entire small bowel, colon, or the total bowel. Most patients find the taste of these flavored mixtures tolerable, but they dislike the heavy texture of the barium.

Concentrated barium suspensions ranging from 50% to 210% weight/volume (wt/vol) are frequently used for traditional radiographic imaging. Dilute suspensions ranging from 1.5% to 5% weight/volume (wt/vol) are typically used for CT studies.

The quantity and concentration of barium sulfate suspension administered to the patient will depend on the selected procedure. In general, upper GI studies will administer the contrast agent just prior to imaging, whereas lower GI studies recommend intake several hours prior to the procedure. For total bowel opacification, the patient should consume contrast agent the night preceding the examination, additional agent a few hours prior to examination, and a third dose approximately 15 minutes prior to examination.

Diatrizoate. Diatrizoate is a water-soluble, ionic monomer. It is commercially available as the meglumine salt, sodium salt, or as fixed combinations of the two salt forms. These triiodobenzoic acid salts contain 47% organically bound iodine.

Numerous products with various concentrations of one or two of the salt forms are available for various imaging procedures. Indicated uses include angiography, venography, excretory urography, retrograde cystourethrography, retrograde or ascending pyelography, operative, T-tube, or percutaneous transhepatic cholangiography, splenoportogra-phy, arthrography; discography, radiographic examination of the GI tract when barium sulfate is contraindicated (i.e., suspected perforation of the GI tract), adjunct contrast enhancement in CT of the torso (dual contrast study), and hys-terosalpingography.


Diaztriazoate Meglumine

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  • dimitri
    Why additives is used in contrast media?
    8 months ago

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