Iodine is the only element that has proven satisfactory as an intravascular radiographic contrast medium (RCM). Iodine produces the radiopacity while the other portions of the molecule act as the carriers for the iodine, improving solubility and reducing the toxicity of the final compound. Organic carriers of iodine are likely to remain in wide-spread use for the foreseeable future. During image-guided injection, injection of RCM can prove invaluable in determining the final location and distribution of the injectate (Figs. 3-1, 3-2 and 3-3). Use of RCM can improve the safety of many techniques by allowing for detection of intravascular (Figs. 3-4 and 3-5), subdural (see Fig. 3-2), or intrathecal (see Fig. 3-3) needle location before a local anesthetic or steroid is placed.

Currently, there are four chemical varieties of iodinated RCM in widespread use: ionic monomers, nonionic monomers, ionic dimers, and nonionic dimers. On intravascular injection, all four are redistributed rapidly via capillary permeability to the extravascular space, they do not enter the interior of blood or tissue cells, and they are rapidly excreted, more than 90% eliminated via glomerular filtration within 12 hours of administration. None of the four varieties have marked pharmacologic actions. All RCM agents come in a range of concentrations that vary in their radiopacity and viscosity. Because iodine is the element that is responsible for the radiopacity, the iodine concentration in milligrams per milliliter represents the radiopacity. The nonionic monomers are now used almost exclusively in pain medicine; the nonionic dimers offer increased radiopacity at low osmolar concentrations, but are not in widespread clinical use and offer questionable clinical advantages.

There are several important chemical properties that determine the characteristics of RCM in clinical use. Osmolality depends on the number of particles of solute in solution and is highest for the ionic contrast agents. Adverse reactions, particularly discomfort on injection, have been reduced dramatically with the advent of low-osmolar RCM. Contrast media with osmolality below 500 mOsm per kg of water are virtually painless. Radiopacity depends on the iodine concentration of the solution and, therefore, on the number of iodine atoms per molecule and the concentration of the iodine-carrying molecule in solution. Digital subtraction electronically enhances the image, reducing the amount of contrast medium needed by a factor of twofold to threefold. With use of digital subtraction, RCM with as little as 150 to 200 mg per mL of iodine can be used even for intra-arterial use. Ionic molecules dissociate into cation and anion in solution. Nonionicity, or a molecule that does not dissociate in solution, is essential for myelography or use along the neuraxis, where inadvertent placement within the CSF is possible during injection. The chemical properties of common RCM used in clinical practice are compared in Table 3-1.

The most frequently used ionic monomers are diatrizoate (Urografin), iothalamate (Conray), and metrizoate (Isopaque). All ionic monomers are the salts of meglumine or sodium as the cation and a radiopaque tri-iodinated fully substituted benzene ring as the anion. The ionic monomers are still used for intravenous pyelography and similar applications; however, they have been completely replaced by the low-osmolar, nonionic RCM for many applications, including intrathecal administration. The most common nonionic monomers in clinical use include iodixanol (Visipaque), iohexol (Omnipaque), iopamidol (Isoview), and ioversol (Optiray); only iohexol and iopamidol are labeled for intrathecal use. The nonionic monomers appeared in the 1970s, and now represent the most common RCM in clinical use. They are more stable in solution and less toxic than the ionic monomers.

Modern contrast agents have reduced, but not eliminated, the risk of adverse reactions. To minimize the risk, RCM should be used in the smallest concentrations and in the smallest total dose that will allow adequate visualization. Adverse reactions associated with RCM can be divided into idiosyncratic anaphylactoid reactions, nonidiosyncratic reactions, and combined reactions. The risk of adverse reactions is significantly greater with use of high-osmolar, ionic agents when compared with low-osmolar, nonionic agents. This discussion is limited to the risks associated with low-osmolar, nonionic agents because they are used almost exclusively in pain medicine applications.