Iodinated contrast

Anaphylactoid reactions occur rarely,[9][10][11] 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.[12][13] Pretreatment with corticosteroids has been shown to decrease the incidence of adverse reactions.[14][15]

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, albuterol inhaler, or subcutaneous or IV epinephrine, plus diphenhydramine may be needed. If respiration is compromised, an airway must be established prior to 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.[16] 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.[17] 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.[18]

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.[19] 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.

The term "iodine allergy" should be omitted because this kind of allergy does not exist.[20] 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.[21] 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 intolerance to alcohol 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.[22] Those with history of severe contrast reaction will have six-fold increase risk of adverse reaction. Those with history of asthma will have six-fold increased risk to low-osmolar contrast media and 10-fold increased risk to high-osmolar contrast media.[23]

Over 85% of patients with seafood allergies will not have an adverse reaction to iodinated contrast.[21] Finally, there is no evidence that adverse skin reactions to iodine-containing topical antiseptics (e.g., povidone-iodine) are of any specific relevance to administration of I.V. contrast material.[21][24]

IL-2 medication poses no risk for the acquisition of adverse events by radiocontrast agents.[25]

Contrast-induced nephropathy is defined as either a greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL.[26] Iodinated contrast may be toxic to the kidneys, especially when given via the arteries prior to 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.[27]

Iodinated contrast media exposure can potentially cause incident hyperthyroidism and incident overt hypothyroidism."[28][29] 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.[30] Otherwise, for the general population, routine screening with thyroid function tests is generally not feasible.[30]

It has been recommended that metformin, an oral antidiabetic agent, be stopped for 48 hours following the intravascular administration of contrast media and that the use of metformin not be resumed until kidney function has been shown to be normal. The reasoning is that if the contrast medium causes kidney failure (as happens rarely) and the person continues to take metformin (which is normally excreted by the kidneys), there may be a toxic accumulation of metformin, increasing the risk of lactic acidosis, a dangerous complication.[31]

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.[32]

Contrast exposure may interfere with subsequent radioiodine treatment, causing unwanted delays in the management of thyroid cancer.[30]

Previously, beta blockers have been assumed as risk factor for the acquisition of contrast medium-induced adverse reactions/hypersensitivity reactions. Due to recent investigations it became clear that beta blockers do not increase the frequency of adverse reactions in concert with radiocontrast agents.[33]

Iodinated contrast in medical imaging in pregnancy, when orally administered, is harmless.[34] 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 potential harm of free iodide on the fetal thyroid gland,[34] but multiple studies have shown that a single dose of intravenously administered iodinated contrast medium to a pregnant mother has no effect on neonatal thyroid function.[35] Nevertheless, it generally is recommended that radiocontrast only be used if absolutely required to obtain additional diagnostic information that will improve the care of the fetus or mother.[34]

American College of Radiology (ACR) guidelines state that iodinated contrast administration to a breastfeeding mother is considered safe for both the mother and child.[36] 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.[36] Mothers that opt for this for non-emergent exams may also use a breast pump to obtain milk before the exam in order to feed the child during the 24-hour abstinence period.[36]