Iodinated Contrast Media and Their Adverse Reactions

Anaphylactoid/Idiosyncratic Reactions

As the name suggests, the exact etiology for these reactions is less well understood, and they tend to mimic an anaphylactic (allergic) reaction. The proposed mechanism of these reactions includes enzyme induction, causing the release of vasoactive substances such as histamine and serotonin and the activation of a physiologic cascade and eventually the complement system (10).

These are the most frequent type of adverse reactions and may have serious, occasionally fatal, complications. These reactions are more frequent in patients with asthma (5 times), patients with previous reactions (4–6 times), patients with cardiovascular and renal disease, and individuals on β-blockers. Anxiety, apprehension, and fear may play a part in this type of reaction. Such reactions usually begin within 20 min of injection and are independent of the dose administered. Symptoms associated with anaphylactoid reactions are classified as mild (skin rash, itching, nasal discharge, nausea, and vomiting), moderate (persistence of mild symptoms, facial or laryngeal edema, bronchospasm, dyspnea, tachycardia, or bradycardia), and severe (life-threatening arrhythmias, hypotension, overt bronchospasm, laryngeal edema, pulmonary edema, seizure, syncope, and death) (11,12).

Nonanaphylactoid Reactions

Nonanaphylactoid reactions are also called physiochemotoxic or nonidiosyncratic reactions (13). These reactions are believed to result from the ability of the contrast media to upset the homeostasis of the body, especially the blood circulation. These reactions are dependent on the physical properties of the contrast medium such as ionicity (which causes free ions in the circulation, which in turn may disrupt electrical charges associated with nervous or cardiac activity) and osmolality (which causes large shifts in fluid volumes). Increasing iodine concentration also increases the risk of these reactions. Finally, the volume and route of administration of contrast also increase the likelihood of such reactions (larger volume or intraarterial administration are more likely to produce a reaction) (1,14).

The cardiovascular, respiratory, urinary, gastrointestinal, and nervous systems are most commonly affected by physiologic changes produced by contrast media. The symptoms of nonanaphylactoid reactions are warmth, metallic taste, nausea, vomiting, bradycardia, hypotension, vasovagal reactions, neuropathy, and delayed reactions (1).

Patient Selection, Preparation, and Special Circumstances

Before administering contrast media, one should assess the medical history for factors predisposing a patient to contrast reactions. These factors are summarized in Table 2. It should be noted that none of the conditions listed in Table 2 is an absolute contraindication to administering contrast. Consultation with the referring physician and radiologist, on a per-case basis, is necessary to develop guidelines that are in the patient's best interests.

Once the decision to administer contrast has been made, secure access should be obtained. The bore of the catheter should be determined by the rate at which contrast is to be administered and tested with an appropriate saline bolus immediately before injection. All air leaks and bubbles should be removed from the injecting system.

Patient reassurance plays an important role in minimizing contrast reactions. A step-by-step explanation of the procedure with expected changes (a mild warm flushing at the site of injection, which spreads over the body and may be particularly intense in the perineum, and metallic taste that pass away quickly) is reassuring to the patient. Additionally, in the case of nervous patients, encouraging continuous conversation and feedback from the patient during the scan, if possible, is also helpful.

Premedication

A test dose and compulsory premedication are seldom used in current practice (15). Premedication is considered in those patients who require intravenous contrast but have had previous reactions. Although patients who have shellfish allergies are more prone to contrast reactions, this is more likely caused by cross-reactivity between shellfish and contrast media, rather than by the patient's inherent allergic tendency (similar to the reason why patients with asthma are more prone to reactions) (16). Various premedication protocols involving the use of steroids and antihistaminics are summarized in Table 3 (17,18). Steroid premedication is relatively contraindicated in active tuberculosis, diabetes mellitus, peptic ulcer disease, acute lymphoblastic leukemia, and non-Hodgkin's lymphoma.

Extravasation

Extravasation can occur during hand or power injection in 0.1%–0.9% of cases but is more common in the latter. The elderly, infants, children, patients with altered consciousness, and those with underlying vascular disease are more prone to extravasation. Small extravasations of contrast media usually produce a local inflammatory response in the skin, without serious sequela. Larger volumes (50–75 mL) may produce tissue damage from chemotoxicity or resultant compartment syndrome (19,20).

Patients usually present with persistent burning and swelling at the injection site. Assessment of the patient's pulse distal to the injection site and documentation of initial swelling and erythema are essential in early management. Smaller extravasations may be managed with elevation and cold compresses. In cases with persistent swelling, pain, and discoloration, it is best to consult a surgeon. Complications of contrast extravasation tend to be more severe with higher-osmolality contrast agents (19,21,22).

Air Embolism

Air embolism is a potentially fatal but rare complication of intravenous contrast injection. Symptoms include dyspnea, cough, chest pain, pulmonary edema, hypotension, and neurologic deficit. Treatment includes administering 100% oxygen and placing the patient in a left lateral decubitus (left side down) position and, if needed, providing hyperbaric oxygen (23–27).

Additional Reactions

Contrast reactions are classified as mild (which are usually self-limiting and resolve quickly with reassurance and without additional intervention), moderate (which take longer to resolve and may progress; these usually require medical intervention), and severe (which are life-threatening and always require medical intervention).

Management of contrast reactions follows the lines of usual resuscitation measures used in current medical practice. A detailed description of managing contrast reactions is beyond the scope of this article, but the basic principles of their management and some common management strategies have been summarized in Tables 4 and 5 (1,5,28–31). Guidelines for suggested medications and information to be displayed where contrast would be administered are summarized in Table 6.

Delayed Reactions

Delayed reactions occur between 1 h and 7 d after injection of contrast in approximately 2% of patients (31). Common delayed reactions are flulike symptoms (fever, chills, rashes, pruritus, and nausea). Less-frequent manifestations are parotitis, joint pain, and depression. Many of these are not considered to be related to contrast media at all, but the skin rashes have been attributed to contrast media (31). Delayed reactions are more common in patients with interleukin-2 chemotherapy and in those injected with nonionic dimers (31,32). The reactions usually resolve spontaneously and are treated with supportive therapy: analgesics to treat headaches, antipyretics for fever, meperidine for rigors, and isotonic fluid for hypotension.

Contrast-Induced Nephrotoxicity

Contrast agent–related nephropathy is an elevation of the serum creatinine level by more than 0.5 mg/dL or more than 50% of baseline 1–3 d after contrast injection. The incidence of contrast agent–related nephropathy is estimated to be 2%–7% (33,34). Causes for contrast-induced nephrotoxicity include renal hemodynamic changes resulting in renal vasoconstriction or direct contrast-induced tubular toxicity. Risk factors of and methods for preventing contrast-induced nephropathy are summarized in Table 7. The risks and benefits of nephrotoxicity must be weighed carefully before administration of intravenous contrast in these situations. Contrast-induced nephrotoxicity is best handled by a nephrologist.

Non–insulin-dependent patients with diabetes who are on biguanide therapy (metformin, glyburide, glucophage, and metaglip) are at particular risk of contrast-induced nephrotoxicity. Medications must be stopped immediately after the contrast injection, and they should be restarted by the primary physician 48 h later only after confirmation of normal renal and liver function tests (35).

Pregnant and Nursing Patients

The safety of intravenous iodinated contrast media during pregnancy has not been established. Contrast media can cross the placenta, enter fetal circulation, and cause thyroid disorders (36–39). Intravenous contrast should be used in pregnancy only if the possible benefits outweigh the risks. Any elective examination requiring intravenous contrast should be deferred until the postpartum period. There is now believed to be an extremely low passage of contrast into the fetal circulation, of which a very small amount is actually absorbed by the infant; although some mothers may cease breast-feeding for 24 h after contrast administration, the basis for this practice is questioned (39).