US Pharm. 2012;37(5):HS-14-HS-16.
Intravenous radiocontrast, or IV dye, is
used for many different diagnostic procedures to enhance the images in
various radiologic studies. Examples of studies include computed
tomography (CT) scans, angiograms, and pyelograms. These diagnostic
procedures are done on a daily basis in hospital interventional
radiology and cardiology departments around the world. In general, they
are used to enhance the visibility of blood vessels.1
There are two basic types of contrast
media that are used for most radiologic studies: ionic high-osmolality
contrast media and nonionic low-osmolality contrast media. The latter
has become the preferred form of IV dye in recent years, given its
better safety record, especially for women who are breastfeeding.
However, it is far more expensive than high-osmolality contrast media.
Allergy reactions to IV dye are common, can range from mild to
moderate, and can sometimes be life-threatening.1
It is believed that people who have an
allergy to seafood (shellfish) may show an allergy to contrast media as
well, due to the presence of iodine in both. We will briefly review the
types, applications, and allergy profile of these products in this
Types of Radiocontrast Media
Both high-osmolar contrast media (ionic)
and low-osmolar contrast media (nonionic or organic) agents contain
iodine and are administered intravenously. Most intravascular contrast
media are derivatives of tri-iodobenzoic acid. The iodine molecule is
an effective x-ray absorber in the energy range where most clinical
systems operate. Iodinated contrast media are the most efficient
products to enhance the visibility of vascular structures and organs
during radiographic procedures. The ionic type creates more charged
particles and causes a high osmolality in blood, which may cause a
potentially life-threatening contrast media reaction in some
individuals with medical conditions. The nonionic agents generate less
dissociation and particles and decrease this risk, but are much more
expensive. The nonionic contrast media are much more widely used today.
The iodine concentration of contrast media is determined by the number
of iodine molecules in milligrams present in a milliliter of a solution
Concentration of any contrast media
agent determines how radiopaque the agent will be. The higher the
iodine concentration, the better the chance that more x-ray photons
will be absorbed. Therefore, that particular contrast agent may be more
radiopaque than a comparable low-iodine concentrated agent.
The osmolality of a solution is the
measurement of the number of molecules and particles in a solution per
kilogram of water. In other words, osmolality can be described as a
measurement of the number of molecules that can crowd out or displace
water molecules in a kilogram of water. The radiographic significance
of the osmolality value of contrast media is that it is higher than the
osmolality value of blood plasma. Any solution that has an osmolality
value greater than blood plasma is said to be a hyperosmolar solution.
Therefore, ionic and nonionic contrast media are hyperosmolar solutions
when compared to blood plasma.
Since certain radiographic procedures,
such as myelography, cannot use ionic contrast media, the discovery of
nonionic contrast media in 1974 (e.g., metrizamide) revolutionized
Contrast Media Applications
Examples of currently used ionic and
nonionic contrast media are perflutren-protein type-A microspheres
injection (Optison), iohexol injection (Omnipaque), and nonionic
iodixanol injection (Visipaque).
Optison is used in patients with
suboptimal echocardiograms to opacify the left ventricle and to improve
the delineation of the left ventricular endocardial borders.
Omnipaque is used for angiocardiography;
aortography including studies of the aortic root, aortic arch,
ascending aorta, and abdominal aorta and its branches; contrast
enhancement for CT scan of head and body imaging; IV digital
subtraction angiography (DSA) of the head, neck, abdominal, renal, and
peripheral vessels; peripheral arteriography; and excretory urography.
Nonionic or organically bound iodine
contrast media such as Visipaque (270 mgI/mL) are used for DSA.
Visipaque Injection (320 mgI/mL) is used for angiocardiography,
peripheral arteriography, visceral arteriography, and cerebral
arteriography. Visipaque Injection (270 mgI/mL and 320 mgI/mL) is
indicated for CT of the head and body (excretory urography). Visipaque
Injection (270 mgI/mL) is also indicated for peripheral venography.
Another example of the nonionics is Isovue-300 (iopamidol), which is
used to help diagnose
certain disorders of the heart, brain, blood vessels, and nervous system.1,3
Dosing and Administration
It is reported that the calculation of
contrast media dose and injection rate on the basis of lean body weight
leads to increased patient-to-patient uniformity of hepatic parenchymal
and vascular enhancement. This is likely related to the greater
perfusion of contrast media to solid organs, muscles, and vessels
compared with the highly variable but poorly perfused adipose tissue.
As an example, the volume and injection rate of contrast material
administration based proportionately on a 70-kg man with 25% body fat
or a 70-kg woman with 30% body fat is about 45 g iodine IV at 0.9 g/sec.4
The rate or speed of contrast media
injections may increase the risk of an adverse reaction. Also, the
viscosity or thickness of the contrast media can cause resistance to
its flow. The viscosity is related to the concentration, the size of
the molecules in a specific contrast agent, and the temperature of the
contrast agent. Contrast media with higher viscosity values should be
injected at a slower rate. Heating the contrast media, usually to body
temperature, reduces viscosity. Iodine concentration, viscosity,
temperature of the contrast media, catheter inner diameter, catheter
length, and the number of catheter holes are all factors that influence
contrast media flow.1
In most cases, shortly after infusion,
iodinated contrast media cause a warming sensation throughout the body.
In certain areas of the body this feeling is more pronounced. Patients
receiving contrast media via IV typically experience a hot feeling
around the throat, and this hot sensation gradually moves down to the
Reactions to IV dye are observed in 5%
to 8% of patients who receive them. Mild reactions include a feeling of
warmth, nausea, and vomiting. Generally, these symptoms occur only for
a short period of time and do not require treatment. Moderate
reactions, including severe vomiting, hives, and swelling, occur in 1%
of patients receiving contrast media and frequently require treatment.
Severe, life-threatening reactions, including anaphylaxis, occur in
0.1% of people receiving contrast media, with an expected death rate of
one person in every 75,000. The most severe reactions, including death,
have been reported to occur at similar rates with both types of
Reactions to contrast media are not a
true allergy, but rather a pseudoallergy in nature, meaning that there
is no allergic antibody present that causes the reaction. Rather,
contrast media act to directly release histamine and other chemicals
from mast cells. The iodine concentration has an effect on the severity
of an adverse reaction. The higher the iodine concentration, the
greater the risk of an adverse reaction.9
Iodinated contrast media are toxic to
the kidneys and kidney functions. The serum creatinine of the patient
receiving a dose should be monitored before the procedure. In addition,
the estimated glomerular filtration rate (eGFR) should be no lower than
30 mL/min in patients receiving iodinated contrast, and discretion
should be used in patients with eGFR less than 45 mL/min. Following
injections with extra fluids is highly recommended.1
Numerous studies have shown that
although iodine is common in contrast media, iodine is not the cause of
allergic reactions. Certain proteins in seafood, rather, are the cause
of allergy in patients with seafood allergies. It is noted that true
allergic effects are by definition immunoglobulin E–related, and
studies have shown that contrast media cause no such reaction in vivo.
Therefore, contrast media or the iodine is not likely to act as an
Radiocontrast Media Allergy Diagnosis
Skin testing and RAST
(radioallergosorbent test) have not been helpful in the diagnosis of
contrast media allergy. Small “test” doses are also not helpful, with
reports of severe, life-threatening reactions occurring even at such
amounts. Severe reactions to larger doses of contrast media have been
observed after a person tolerated a small dose of IV dye. Therefore,
the diagnosis of contrast media allergy is made only after symptoms
have occurred. Otherwise, it is only possible to determine that a
person is at increased risk of a reaction to contrast media based on
the risk factors outlined below.6
Allergy Prevention and Treatment
As mentioned above, the purpose of using
these contrast agents is for diagnosis, but like any medical procedure
in any radiological study, the right dose or volume of contrast media
needs to be determined prior to a procedure. The total volume or dose
is dependent upon several factors: iodine concentration of the contrast
media; type of injectable contrast media (ionic or nonionic); patient’s
body weight, anatomical structures or regions; speed of the injection;
and age or disease process that could increase the risk of an adverse
reaction. The treatment of an acute reaction to contrast media is no
different from any other anaphylactic reaction. Treatment may include
injectable epinephrine and antihistamines, as well as the use of IV
fluids for low blood pressure and shock.7
Contrast media reactions can be prevented by a test dose
for the intended contrast or the use of an alternative; the use of
nonionic versus ionic media if applicable; and the use of certain
medicines prior to the administration of contrast media such as
prednisone 50 mg orally taken at 13, 7, and 1 hour prior to procedure,
or diphenhydramine (Benadryl) 50 mg orally, IV or intramuscularly, 1
hour prior to receiving radiocontrast media.7
As mentioned above, people who have
seafood allergy are not at risk if they need to use contrast media. In
addition, people with an allergy to topical iodine cleaners or iodides
are also not at increased risk for reactions to contrast media.
Patients who are at higher risk include those with past reactions to
contrast media (up to 44%); those with asthma; those who have a history
of heart and kidney and thyroid (both hypo- and hyperthyroidism) diseases;
those taking beta-blockers or metformin; and females and the elderly
(appear to be at higher risk for severe reactions).8,11
Note: Timely follow-up of serum creatinine levels in
patients with diabetes who are receiving metformin therapy is highly
important, and monitoring is required by pharmacists. Nearly 4% of
patients with diabetes mellitus and normal renal function may develop
contrast material–associated neuropathy with nonionic contrast media.
Roughly 8% of patients with diabetes receiving metformin, whose
baseline serum creatinine levels are below 1.5 mg/dL, develop an
increased risk of lactic acidosis requiring metformin therapy to be
withheld for at least 48 hours after administration of IV contrast
material. The FDA currently recommends metformin monitoring in patients
who are undergoing radiologic procedures involving administration of IV
1. American College of Radiology (ACR) Manual on Contrast Media. 2010. Version 7.
2. Meth MJ, Maibach HI. Current understanding of contrast
media reactions and implications for clinical management. Drug Saf.
3. Thomson K, Varma D. Safe use of radiographic contrast
media. Australian Prescriber. 2010;33:19-22.
4. Ho LM, Rendon C. Nelson RC, DeLong DM.Determining
contrast medium dose and rate on basis of lean body weight: does this
strategy improve patient-to-patient uniformity of hepatic enhancement
during multi–detector row CT?
5. Boehm I. Seafood allergy and radiocontrast media: are physicians propagating a myth? Am J Med. 2008;121(8):e19.
6. Barrett BJ, Parfrey PS. Preventing nephropathy induced by contrast medium. N Engl J Med. 2006;354:379-385.
7. Tramer MR, von Elm E, Loubeyre P, Hauser C.
Pharmacological prevention of serious anaphylactic reactions due to
iodinated contrast media: systematic review. BMJ. 2006;333:675.
8. Canter LM. Anaphylactoid reactions to radiocontrast media. Allergy Asthma Proc. 2005;26:199-203.
9. Brockow K. Contrast media hypersensitivity: scope of the problem. Toxicology. 2005;209:189-192.
11. Keller DM,
Iodinated contrast media raises risk for thyroid dysfunction.
Arch Intern Med. 2012;172:153-159.
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