MRI Contrast Agents and Adverse Reactions*

Gadolinium chelates have been approved for parenteral use since the late 1980s. Although these agents can be differentiated on the basis of stability, viscosity and osmolality, they cannot be differentiated on the basis of efficacy. These contrast media are extremely well tolerated by the vast majority of patients in whom they are injected. Adverse reactions are encountered with a much lower frequency than is observed after administration of iodinated contrast media.

Adverse Reactions to Gadolinium Contrast Agents
The frequency of all adverse events after an injection of 0.1 or 0.2 mmol/kg ranges from 0.07 to 2.4 percent. The vast majority of these reactions are mild, including coldness at the injection site, nausea with or without vomiting, headache, warmth or pain at the injection site, paresthesias, dizziness, and itching. Reactions resembling an allergic response are very unusual and vary in frequency from 0.004 to 0.7 percent. A rash, hives, or urticaria are the most frequent of this group, and very rarely there may be bronchospasm. Severe, life-threatening anaphylactoid reactions are exceedingly rare (0.001 to 0.01 percent). In an accumulated series of 687,000 doses there were only 5 severe reactions. In another survey based on 20 million administered doses there were 55 cases of anaphylactoid shock. It would appear that, to date, only one published death has been clearly related to the administration of gadolinium-based contrast. Other deaths in other series have been ascribed to other diseases or to other drugs, or were thought to be coincidental. Clearly, fatal reactions to gadolinium agents are very rare.

Risk Factors
The frequency of adverse reactions to gadolinium contrast agents is about 2.3 to 3.7 times higher in patients with a history of reactions to iodinated contrast material and about 8 times higher in patients with a previous reaction to gadolinium-based contrast agents. Second reactions to gadolinium-based compounds tend to be more severe than the first. Persons with asthma and various allergies are also at greater risk, with reports of adverse reaction rates as high as 3.7 percent.

In the absence of any widely accepted policy for dealing with patients with prior contrast reactions (especially to gadolinium-based compounds) and the need for subsequent exposure to MR agents, it does seem prudent to at least take precautions. It should be determined if contrast material is necessary, if a different MR contrast agent could be used, and if 12 to 24 hours of premedication with corticosteroids and antihistamines could be initiated. This is particularly applicable in patients with prior moderate to severe reactions.

Nephrotoxicity
Gadolinium agents are considered to have no nephrotoxicity at approved dosages for MR imaging. They can be used in azotemic patients and are dialyzable. MR with gadolinium has been used instead of contrast-enhanced CT in those at risk for developing worsening renal failure if exposed to iodinated contrast material.

Gadolinium agents are radiodense and can be used for opacification in CT and angiographic examinations instead of iodinated radiographic contrast agents. However, there is controversy over whether gadolinium contrast agents are less nephrotoxic at equal-attenuating doses. Caution should be used in extrapolating the lack of nephrotoxicity of intravenous gadolinium at MR dosages to the use of gadolinium for angiographic procedures, including direct injection into the renal arteries. No assessment of gadolinium versus iodinated contrast nephrotoxicity by randomized studies of equal-attenuating doses is currently available.

Pregnancy
At doses considerably higher than recommended in humans, gadopentetate dimeglumine has been shown to retard fetal development in rats, double the incidence of post-implantation loss, and to increase the incidence of spontaneous abortion. It may also have an adverse effect on embryo-fetal development. Therefore, MR contrast using any chelate should only be performed if the potential benefit justifies the potential risk, and then only after obtaining written, informed consent.

Treatment
Treatment of moderate or severe adverse reactions to gadolinium-based contrast media is similar to that for moderate or severe reactions to iodinated contrast media. In any facility where contrast material is injected, it is imperative that personnel trained in recognizing and handling reactions and the equipment and medications to do so be on site or immediately available. Most MR facilities take the position that patients requiring treatment should be taken immediately out of the imaging room and away from the magnet so that none of the resuscitative equipment becomes a hazard.

Extravasation
The incidence of extravasation in one series of 28,000 doses was 0.05 percent. Laboratory studies in animals have demonstrated that both gadopentetate dimeglumine and gadoteridol are much less toxic to the skin and subcutaneous tissues than are equal volumes of iodinated contrast media. For these reasons the likelihood of a significant injury resulting from extravasated MR contrast agent is extremely low.

Serum Calcium Determinations
Some evidence has developed that gadolinium-based MR contrast material might interfere with total serum calcium values determined with standard colorimetric methods (Roche, Dade and Olympus). This interference is not seen using dry slide technology (Vitros). A warning from Roche Diagnostics suggested that colorimetric determination might be erroneously low, especially in patients with impaired renal function who have recently received gadolinium. It appears that the linear chelates Gd-DTPA-BMA (gado-diamide) and Gd-DTPA bis(methoxyethyl) amide (gadoversetamide) are much more likely to cause this artifact than Gd-DTPA (gadopentetate dimeglumine) or the macrocyclic chelates such as Gd-DOTA (gadoterate meglumine).

If an unexpectedly low result for serum calcium is obtained, it should be repeated two days later or checked with atomic absorption spectroscopy which is not affected by gadolinium chelates.

Off-Label Usage
Radiologists commonly use contrast media for a clinical purpose not contained in the labeling and thus commonly use contrast media off-label. Examples include MR angiography, cardiac applications, pediatric applications in patients less than two years of age, and usage in patients with renal failure.

[*Excerpted with permission from the American College of Radiology, Manual on Contrast Media, 5th Edition, 2004; Reprinted with permission of the American College of Radiology. No other representation of this article is authorized without express, written permission from the American College of Radiology.

Also, please see the new version of this document Manual on Contrast Media, Version 6, 2008 - full version available at www.acr.org]

[*American College of Radiology, Manual on Contrast Media, 5th Edition, 2004; Reprinted with permission of the American College of Radiology. No other representation of this article is authorized without express, written permission from the American College of Radiology.]

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