Radiographic contrast media (RCM) contributes important information to the diagnostic process. Actual contrast agents are safe drugs. Adverse reactions are rare, the incidence and severity of side effects decrease with the use of nonionic and low-osmolar contrast media. Adverse reactions are diverse, ranging from mild physiological disturbances to very rare life-threatening anaphylactic or anaphylactoid reactions. Users of contrast agents must be aware of the risk factors and be prepared to promptly manage adverse effects.
Side effects that may occur with intravascular administration of contrast agents are also possible after administration by other paths. Increased risk to an adverse reaction includes patients with a history of a previous reaction to a contrast medium, a known sensitivity to iodine, or a known clinical hypersensitivity (bronchial asthma, hay fever, and food allergies).

See also Contrast-Induced Nephropathy, Iodide-Induced Hyperthyroidism and Idiosyncratic Reactions.

A clinical trial is a controlled study involving human subjects, designed to evaluate prospectively the safety and effectiveness of new drugs or devices or of behavioral interventions.

See also Adverse Reaction and Safety of Contrast Agents.

(LOCM) Low-osmolar contrast media have a wide range of indications due to their lower side effects. The type of contrast media is an important risk factor for an adverse reaction.
LOCM have not completely replaced contrast media with higher osmolality due to their higher cost. Guidelines of professional organizations give recommendations for the selective use of low-osmolar contrast media for certain high-risk patients.
There are ionic and nonionic iodinated contrast materials with low osmolality available:
An adverse reaction occurs in low-risk patients who receive conventional ionic contrast agents more often than in high-risk patients who receive nonionic LOCM.

See also Contrast Enhancement, Biliary Contrast Agents, Safety of Contrast Agents and Contrast-Induced Nephropathy.

Iodinated contrast media contain small amounts of free iodide. Too much free iodide in the blood may cause hyperthyroidism in patients at risk, but contrast medium induced thyrotoxicosis is rare. The free iodide may also interfere with nuclear medicine diagnostic tests and treatment. However, iodinated contrast agents do not affect thyroid function tests (e.g., T3, T4, TSH) in patients with a normal thyroid.
Guidelines were prepared by the 'Contrast Media Safety Committee of the European Society of Urogenital Radiology' and discussed on the Tenth European Symposium on Urogenital Radiology in September 2003.
Tests of thyroid function before the injection of contrast agents may only be indicated in areas with dietary iodine deficiency. Patients with Graves' disease, multinodular goiter with thyroid autonomy, especially elderly and patients who lives in areas of iodine deficiency are at risk to develop thyrotoxicosis after IV contrast medium and should be monitored by endocrinologists after contrast enhanced CT exams. Prophylaxis may offer some protection in selected high-risk individuals but is not generally recommended.
The free iodide of iodinated contrast agents interferes with thyroidal iodide uptake and impedes diagnostic thyroid scintigraphy and radio-iodine treatment of thyroid malignancies for 2 months after administration.

The first-generation contrast agents were all ionic monomers, consisting of a tri-iodinated benzene ring with 2 organic side chains and a carboxyl group. Diatrizoate or iothalamate are common iodinated anions, conjugated with a cation, sodium or meglumine. The ionization at the carboxyl-cation bond makes the agent water soluble.
Ionic monomers have the highest osmolality (high-osmolar contrast media (HOCM) possess an osmolality seven to eight times higher than plasma) of the different groups of contrast agents (CM ratio=1.5) and the lowest viscosity. The osmolality in solutions of ionic monomers ranges from 600 to 2100 mOsm/kg (human plasma = 290 mOsm/kg). These high osmolality is related to some of the adverse reactions. HOCM's have been widely replaced by newer contrast agents with improved tolerability and safety profiles.
Examples of HOCM's are Renografin®-60, Hypaque 76, Hypaque Meglumine, Hypaque Sodium and Conray®.

See also Ionic Contrast Agents.