1. Consider the risk/benefit ratio. Obvious but essential. Is the procedure to be performed optimal for the patient, in his or her current clinical status? That is, can ultrasound (US), a radionuclide study, magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA), or computed tomography (CT) (particularly if it can be done without a contrast agent) be performed instead?

2. There are NO absolute contraindications to the use of an iodinated contrast agent. Several cautions, however, are important, in regard to the following issues:

a. Should a contrast agent be administered?

b. Are there any significant risk factors?

c. Is administration of a contrast agent likely to be safe?

d. What class of agent should be given?

3. Relevant history, to determine whether or not there is an increase in the risk of a contrast reaction.

a. Has there been prior contrast administration? Concern: Many reported prior “reactions to contrast” are actually not contrast-related, but a true reaction does increase the risk (by 10% to 20%) of a recurrent contrast reaction.

(1) If so, did a reaction occur?

(2) What did the reaction specifically consist of? Many “reactions” are a reflection of anxiety about the procedure or a physiologic response (e.g., nausea, hot feeling) rather than an actual reaction to the contrast agent.

(3) Which specific contrast agent was used?

b. Are there any active, serious allergies (e.g., anaphylaxis to multiple medications)? Concern: increased risk of a contrast reaction. A history of shellfish allergy does NOT increase the risk of a reaction to iodinated contrast agents.

c. Is there active asthma that currently requires treatment? Concern: worsened bronchospasm secondary to contrast or perhaps to anxiety

d. Is there significant cardiac disease (e.g., pulmonary hypertension, class III-IV congestive heart failure [CHF], class III-IV angina, tight aortic stenosis)? Concern: acute cardiac decompensation secondary to volume load

e. There is a theoretical concern about those with cerebrovascular disease because of decreased cerebral perfusion with hypotension, although there are no clinical studies that suggest that this is a real risk.

f. Is there a history or risk of renal dysfunction (urinary tract disease, paraproteinemia, or diabetes mellitus)? Is the patient on any nephrotoxic medications or metformin? (see Chapter 65). Concerns: With renal disease (+/− diabetes), there is risk of contrast-induced nephropathy (CIN); with paraproteinemia, concern is acute renal failure. If the patient is on metformin AND has renal dysfunction, concern is lactic acidosis.

4. Physical examination

a. Assess patient’s ability to understand and cooperate with examination.

b. Assess level of anxiety.

c. Assess level of hydration.

d. Obtain baseline vital signs.

5. Laboratory assessment

a. Blood urea nitrogen (BUN) and creatinine (Cr) only if there is concern about renal function (e.g., history of renal stone, benign prostatic hyperplasia [BPH], bladder prolapse, recurrent urinary tract infections [UTIs]), diabetes mellitus; patient on metformin (elevated serum Cr remains an absolute contraindication to the use of this common medication).

b. Complete blood count (CBC) and urinalysis (for proteinuria, specific gravity) if there is concern about hydration, general status

c. For concerns regarding bleeding risk of procedure, practical parameters for an interventional procedure are an adequate platelet count and activated partial thromboplastin time (APTT) and international normalized ratio (INR) within normal limits. Not a limitation to contrast administration in itself (e.g., with CT)

6. Informed consent is necessary prior to any invasive procedure that carries “significant risk”; what constitutes significant risk is somewhat subjective. It is widely accepted that specific informed consent for contrast administration is NOT necessary. Most centers, however, do utilize a patient information sheet that asks for relevant information from patients (this is reviewed, and as appropriate, brought to the attention of the responsible physician). This sheet obtains relevant history and risk factors, indicates the risks, and gives the patient the opportunity to ask any questions:

a. Tailor consent to examination but include risks of contrast administration and the greater risks of conscious sedation and of the procedure itself.

b. Physician should be available to answer questions.

c. Risk of severe, life-threatening contrast reaction is less than 1:10,000. Risk of direct mortality from a contrast agent is substantially less than 1:120,000.

1. Minimize the volume of contrast/iodine as much as possible, without compromising image quality and diagnostic information. Although an increase in volume and iodine content usually improves image quality, it may NOT add useful information, or may actually obscure certain lesions (i.e., prevent observation of detail through a vessel). Also, increased volume may add risk in patients with limited cardiac output or renal failure. Increased iodine concentration (e.g., 300 mgI per mL vs. 350 mgI per mL) increases osmolality, which may increase risk as well.

2. Conversely, in the absence of specific risks (heart failure, renal dysfunction), contrast volume itself is not a limitation: There is no direct relationship between increased volume of contrast and adverse events.

3. Emergency equipment to treat reactions, such as cardiopulmonary arrest, as well as personnel fully trained to use this equipment (advanced cardiac life support [ACLS] certification or the equivalent) must be readily available.

4. There are three basic kinds of contrast agents, all based on a tri-iodinated benzene ring (1,6):

a. High-osmolality contrast agents (HOCA) are very safe and less expensive than the other two categories. They were widely used parenterally for over 40 years and are extremely safe but have the highest incidence of minor side effects (e.g., pain and heat, nausea, urticaria); they are now infrequently used. They are monomers (i.e., a single fully substituted 6 carbon ring) with an osmolality of 1,200 to 2,000 mOsm per kg, depending primarily on iodine content but also on the specific formulation. All are ionic (i.e., in solution, they dissociate to an anion and a cation) of the three classes.

b. Low-osmolality contrast agents (LOCA) have an osmolality of 450 to 600 mOsm per kg, depending on iodine content and specific formulation. All but one are nonionic (i.e., nondissociating) monomers. Ioxaglate (Hexabrix, Guerbet, Villepinte, France) is an ionic dimer. It is rarely used in the United States currently. As a class LOCA cause less pain and heat and have fewer minor side effects but have similar overall mortality risk. They are less nephrotoxic in patients with compromised renal function. LOCA are almost universally used preferentially to HOCA for most intravenous (IV) and intraarterial (IA) (including intracoronary) contrast administration.

c. Isotonic contrast agents. Only one, iodixanol (Visipaque, GE Healthcare, Princeton, NJ), is currently available in most of the world. It is available in formulations with an iodine content of 280 or 320 mgI per mL; both have an osmolality equal to that of blood (about 280 mOsm per kg). It causes almost no discomfort on injection and fewer cardiac alterations. It may be associated with a lower risk of CIN but a higher risk of delayed cutaneous reactions. Cost is generally about twice that of most LOCA.

1. Incidence varies with route of administration, presence or absence of specific risk factors, and the type of agent. Incidence also depends on definition used for “reaction,” “complication,” or “adverse event” (1,2,3,4,5,6,7,8,9,10):

a. Life-threatening reactions occur in fewer than 1 in 1,000 patients (probably < 1:10,000).

b. Mortality associated with contrast injections is usually primarily related to underlying health factors (severe CHF, major trauma, general debilitation). Mortality does rarely occur in otherwise generally healthy patients, in fewer than 1:120,000 cases.

2. Risk factors for reactions

a.

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