Iodinated contrast agents may cause allergic reactions,
contrast-induced nephropathy,
hyperthyroidism, and possibly
metformin accumulation. However, there are no absolute contraindications to iodinated contrast, so the benefits need to be weighed against the risks. Hypersensitivity towards iodinated contrast agent is associated with increase in
histamine and
tryptase concentration in blood.
Diphenhydramine (Benadryl) 50 mg orally or intravenously one hour before contrast administration can reduce the risk of
urticaria,
angioedema, and respiratory symptoms. An observational study conducted across 133,331 patients concluded that iodinated contrast injected through veins has more hypersensitivity reactions than when injected through arteries. However, the cause for this phenomenon is unknown. In people with
myasthenia gravis, older forms of iodinated contrast have caused an increased risk of exacerbation of the disease, but modern (low-osmolar) forms have no immediate increased risk.
Hypersensitivity reactions Anaphylactoid reactions occur rarely, but can occur in response to injected as well as oral and rectal contrast and even retrograde
pyelography. They are similar in presentation to
anaphylactic reactions, but are not caused by an IgE-mediated immune response. Patients with a history of contrast reactions, however, are at increased risk of anaphylactoid reactions. Pretreatment with corticosteroids has been shown to decrease the incidence of adverse reactions. Anaphylactoid reactions range from
urticaria and itching, to
bronchospasm and facial and laryngeal
edema. For simple cases of urticaria and itching, an oral or intravenous antihistamine such as
diphenhydramine is appropriate. For more severe reactions, including bronchospasm and facial or neck edema, an albuterol inhaler, or subcutaneous or IV epinephrine, plus diphenhydramine, may be needed. If respiration is compromised, an airway must be established before medical management. Anaphylaxis to ionic (high osmolar) contrast agent injections occurred in two clusters of reactions on two occasions (1983 and 1987) in a single radiology clinic in London, Ontario. On each occasion, these anaphylactic reactions were associated with contamination of the injection by natural rubber components (disposable plastic syringes in the first case and rubber ampoule seals in the second case). The allergenic-toxic rubber leachate was MBT (
mercaptobenzothiazole). This is a known allergen that becomes bound to plasma proteins, creating a hapten-protein complex – a signature mechanism in true IgE drug allergy and true anaphylactic reactions (not "anaphylactoid" reactions). A Japanese syringe manufacturer, Terumo, implicated in syringe-related toxic laboratory cell culture effects in Australia in 1981, was instrumental in pro-actively making Japanese disposable syringes and ampoule seals free of natural rubber. Katayama's 1990 article in
Radiology showed that a new type of nonionic (low osmolar) contrast agent was associated with significantly fewer severe life-threatening reactions than the older ionic (high osmolar) contrast agents. By merchandizing the Katayama series reprints, manufacturers persuaded users worldwide to switch to the almost exclusive use of the expensive nonionic agents. What was unknown to the Katayama researchers was that the ampoule seals of the "safer" nonionic contrast agents were made from artificial rubber, whereas the ionic agents were sealed with natural rubber. In 1987, it was the leaching of allergenic MBT from the rubber seals of ionic ampoules that caused a series of allergic reactions (including anaphylaxis) in a radiology office in Canada. The worldwide hazard of MBT contamination of injections was unknown then and, as the World Health Organization reported it remains as an unknown hazard still – after three decades. The most significant study, proving that injections of ionic (high osmolar) agents are at least as safe as the newer, very expensive nonionic agents, was published in
Radiology in 1997. Lasser did not comment that the marked drop in the incidence of severe reactions with ionic agents was related to the removal of natural rubber contamination from ionic ampoule seals.
Contribution of seafood and other allergies The term "iodine allergy" should be omitted because this kind of allergy does not exist. Seafood "allergy" is not a contraindication for the use of iodinated contrast materials, because in seafood allergy the immune system is directed against the muscle protein
tropomyosin. While iodine levels in seafood are higher than in non-seafood items, the consumption of the latter exceeds that of the former by far, and there is no evidence that the iodine content of seafood is related to reactions to seafood. Available data suggest that seafood allergy increases the risk of a contrast-mediated reaction by approximately the same amount as allergies to fruits or those with asthma. In addition, those with an alcohol intolerance should avoid use of this product due to chemical breakdown similar to ethyl alcohol. Studies show that B.A.C. has been shown to increase exponentially for up to 72 hours after contrast is administered, resulting in altered results of urine, blood, and breath alcohol screens. Those with a history of severe contrast reaction will have a six-fold increased risk of adverse reaction. Those with a history of asthma will have a sixfold increased risk of low-osmolar contrast media and a 10-fold increased risk of high-osmolar contrast media. Over 85% of patients with seafood allergies will not have an adverse reaction to iodinated contrast. IL-2 medication poses no risk for the acquisition of adverse events by radiocontrast agents.
Contrast-induced nephropathy Contrast-induced
nephropathy is defined as either a greater than 25% increase in serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL. Iodinated contrast may be
toxic to the kidneys, especially when given via the arteries before studies such as catheter coronary angiography. Nonionic contrast agents, which are almost exclusively used in
CT scans, have not been shown to cause CIN when given intravenously at doses needed for CT studies.
Effects on thyroid function Iodinated contrast media exposure can potentially cause incident
hyperthyroidism and incident overt
hypothyroidism." Hyperthyroidism is the effect of iodine being a substrate of thyroid hormones, and is then called the
Jod-Basedow phenomenon. The risk is higher in those with an underlying
thyroid disease, such as
toxic multinodular goiter,
Graves' disease, or
Hashimoto's thyroiditis, where thyroid monitoring is indicated. Otherwise, for the general population, routine screening with thyroid function tests is generally not feasible. However, guidelines published by the American College of Radiologists suggest this is not as important for patients who have
normal kidney function and no evidence of acute kidney injury. If kidney impairment is found before administration of the contrast, metformin should be withheld for 48 hours following the procedure and until kidney function has returned to normal. Contrast exposure may interfere with subsequent
radioiodine treatment, causing unwanted delays in the management of
thyroid cancer.
Pregnancy Iodinated contrast in
medical imaging in pregnancy, when
orally administered, is harmless.
Intravenous administration of iodinated radiocontrast agents can cross the
placenta and enter the
fetal circulation, but animal studies have reported no
teratogenic or
mutagenic effects from its use. There have been theoretical concerns about the potential harm of free iodide on the fetal
thyroid gland, Nevertheless, it generally is recommended that radiocontrast only be used if required to obtain additional diagnostic information that will improve the care of the fetus or mother. Still, mothers who remain concerned about any potential adverse effects to the child are recommended to have the option of abstaining from breastfeeding for 24 hours, with continued milk extraction such as by a
breast pump during that period. What is also important, breastfeeding women should be asked whether they want to take a break from breastfeeding after CM administration. ==See also==