Introduction to Contrast Agents

1

What is a radiographic contrast agent?

A radiographic contrast agent is a substance that is administered to a patient during an imaging examination to improve its diagnostic performance. Contrast agents are most often administered via the intravenous (IV) and oral routes for computed tomography (CT) and magnetic resonance imaging (MRI) examinations. However, other routes of contrast administration may be utilized, depending on the particular imaging study to be performed. For example, arteriography requires the intraarterial (IA) administration of contrast material, while arthrography requires the intraarticular injection of contrast material directly into a joint. Intrathecal contrast administration is required for myelography.

A catheter is used to inject the contrast material in some procedures. In hysterosalpingography, a catheter or cannula is placed into the external cervical os to opacify the uterine cavity. In retrograde urethrography, a Foley catheter is placed at the urethral meatus in a male to inject contrast material to evaluate the urethra. In cystography, injection of contrast material is performed through a catheter placed in the urinary bladder. In retrograde pyelography, contrast material is administered through catheters placed into the renal collecting systems with cystoscopic guidance to evaluate the pyelocalyceal systems and ureters in patients who cannot receive intravenous contrast material.

The administration of radiographic contrast agents by the various routes mentioned above is widely used in clinical practice, and is usually not associated with any adverse effects. However, prior to administering contrast material, attention must be given to the clinical indication for the procedure, and to the clinical status of the patient in order to minimize adverse side effects and to maximize diagnostic yield. It is essential that in a facility where contrast material is routinely administered for imaging studies, trained personnel along with appropriate equipment and medications be available on site to manage a contrast reaction, should one occur.

2

What types of contrast agents are available for intravascular use?

Iodinated contrast agents are used in all studies where x-rays are utilized, such as CT, intravenous urography (IVU), and all fluoroscopic studies. These can be broadly classified based on osmolality (high, low, or iso-), ionicity (ionic or nonionic), and the number of benzene rings in the chemical structure (monomeric or dimeric). Nonionic contrast agents are associated with less discomfort during intravascular administration and fewer adverse reactions compared to ionic contrast agents. Therefore, nonionic low osmolal or iso-osmolal contrast agents are almost exclusively used in current clinical practice for intravascular injections, particularly in developed countries.

Gadolinium-based contrast agents are used in MRI studies and can be classified based on ionicity (ionic or nonionic), the chelating ligand (macrocyclic or linear), and the pharmacokinetics (extracellular or organ specific). Ionic and nonionic agents have relatively little or no difference in acute reactions and discomfort.

There are other types of intravascular contrast agents, such as iron oxide–based contrast agents that are used in MRI studies and microbubble contrast agents that are used in ultrasonography (US) studies; these will not be discussed because they are beyond the scope of this chapter.

3

How common are acute adverse reactions to intravascular contrast material?

Acute adverse events occur in up to 0.7% of patients who receive intravascular low or iso-osmolality iodinated contrast material, and in up to 0.04% of patients who receive gadolinium-based contrast material.

Most adverse reactions to contrast agents are mild and not life-threatening, usually requiring only observation, reassurance, and/or supportive measures. Severe and potentially life-threatening adverse events occur rarely and unpredictably, most often within the first 20 minutes following contrast administration.

4

What are the categories of acute adverse reaction to contrast agents?

Allergic-like reactions, rather than true allergies, are seen with radiographic contrast administration and are referred to as anaphylactoid reactions. These are not true hypersensitivity reactions, and immunoglobulin E (IgE) antibodies are not involved. The clinical manifestations may be similar to allergic reactions (such as hives or bronchospasm), but these reactions are often idiosyncratic and prior sensitization is not required, unlike with true allergies. These reactions are independent of the dose and concentration of the contrast agent. A history of prior allergic-like contrast reaction may indicate the need for corticosteroid premedication prior to future contrast-enhanced studies that utilize a similar contrast agent.

Physiologic reactions to contrast agents are associated with the dose, molecular toxicity, and physical and chemical characteristics of the contrast agent. A history of a prior physiologic contrast reaction does not indicate the need for future corticosteroid premedication.

For a detailed classification of acute adverse reactions to contrast agents, see Table 6-1 .

5

What are the 5 important immediate assessments that should be made when evaluating a patient for a potential contrast reaction?

• 1.

  How does the patient look (e.g., level of consciousness and appearance of the skin)?

• 2.

  How does the patient's voice sound? Can the patient speak?

• 3.

  How is the patient's breathing?

• 4.

  What is the patient's pulse strength and rate?

• 5.

  What is the patient's blood pressure?

For full details regarding the treatment algorithms for acute contrast reactions, which are beyond the scope of this chapter, please see the American College of Radiology (ACR) Manual on Contrast Media ( http://www.acr.org/quality-safety/resources/contrast-manual ).

6

What are some risk factors that predispose patients to acute adverse contrast reactions?

• Prior allergic-like reaction to contrast material. (Patients with a history of prior severe contrast reaction have an ≈5- to 6-fold increased risk of a future contrast reaction.)

• History of severe allergies or reactions to other agents (food or medications), especially when to multiple agents.

• History of asthma, bronchospasm, or atopy.

• History of cardiac or renal disease.

7

When do adverse reactions to intravascular iodinated contrast material usually occur?

Most reactions to intravascular iodinated contrast occur within 1 hour of intravenous administration. However, delayed adverse reactions may occasionally occur between 1 hour and 1 week following contrast administration. Such delayed reactions are seen more commonly in young adults, women, and patients with a history of allergy, are most commonly cutaneous (e.g., urticaria, rash, or angioedema), and are typically mild to moderate in severity and self-limited. The incidence of delayed allergic-like reactions has been reported to range from 0.5% to 14% and may occur more commonly with iso-osmolal dimeric contrast agents.

8

What is iodine “mumps”?

Iodine “mumps” is sialoadenopathy or salivary gland swelling that may rarely occur in delayed fashion following iodinated contrast administration.

9

When is premedication indicated prior to contrast administration?

The primary indication for premedication prior to contrast-enhanced imaging is the pretreatment of patients at increased risk for an acute allergic-like reaction to contrast material. Premedication generally involves the administration of corticosteroids, sometimes in conjunction with H1 blockers.

At our institution, indications for premedication include:

• Prior moderate or severe allergic-like reaction to contrast material.

• Prior intravenous contrast reaction requiring administration of epinephrine.

• Prior life-threatening reaction to any allergen or medication.

• Presence of asthma with active wheezing.

• Presence of asthma requiring intubation in the last 3 months.