Iodine-containing contrast medium

Author: Prof Stacy Goergen*

What are the generally accepted indications for ICCM?

Iodine-containing contrast media (ICCM) are widely used in medical imaging to make hollow structures, such as blood vessels, the gastrointestinal tract, the subarachnoid space around the brain and spinal cord, and the interior of joints, visible on imaging studies like CT scans, angiograms, myelograms and arthrograms. ICCM can also be used to assess organ perfusion (e.g. the brain) and to reveal disease in solid organs, such as the liver. For example, liver tissue affected by metastatic disease has differential ICCM uptake when compared with normal liver parenchyma.

What are the prerequisites for having ICCM injection?

The main prerequisite for ICCM injection involves risk assessment for:

• contrast-associated allergy/anaphylaxis; and
• for potential contrast-associated renal impairment.

A simple patient questionnaire created by the Royal Australasian and New Zealand College of Radiologists will be given to the patient before the procedure. Referrers can download, print and refer to this questionnaire, enabling them to note any relevant clinical information reflecting these questions on the referral form. The practice or hospital should be made aware of any patient risks at the time of scheduling of elective procedures/tests.
These questions are:

1. Have you had a reaction to ICCM before?
   It is helpful if you can describe what happened (For example, a rash, breathing difficulties, vomiting or an asthma attack) and the hospital or practice where this occurred, if you know it.
2. Do you have asthma?
   Risk of an allergic-type or anaphylactic reaction to ICCM is increased by approximately 10-fold in patients with asthma.
3. Are you taking medications containing beta-blockers? This is usually for high blood pressure or anxiety
   Beta-blockade can reduce or eliminate the effectiveness of adrenaline in the event of an anaphylactic reaction.
4. Do you have allergies to food, medications, pollen, animals or anything else?
   Multiple allergies will increase the risk of an anaphylactic reaction to ICCM, but less than the increased risk associated with asthma.
5. Do you have diabetes?
   Patients with diabetes will need a recent estimated glomerular filtration rate (eGFR) estimate before ICCM. If the patient is clinically ‘stable’ and has had no clinical events/illnesses that could reasonably be expected to result in a decrease in renal function since the last renal function testing estimate, it is acceptable for the test result to be weeks to months preceding the ICCM administration. The more unwell the patient has been before the ICCM, the more recent the eGFR estimate needs to be because of the potential for renal function to have acutely decreased.
6. Do you have poor or reduced kidney function or kidney disease?
   The recency of eGFR estimation in patients with known renal function impairment should be dictated as above (see point 3.). Patients with stable eGFR above 30 mL/min have little or no risk of contrast-related acute kidney injury and no special preparation, in the form of intravenous periprocedural hydration with normal saline, is generally required in this group of individuals. Patients at some risk of contrast induced acute kidney injury (CI-AKI) are those with eGFR lessthan30 mL/min or actively recovering or declining renal function, usually due to current medical illness. Patients in this situation need to be ‘flagged’ with the imaging department or practice as periprocedural hydration; substitution of other imaging tests that do not require ICCM will be considered by the radiologist in discussion with the referrer. However, there is no absolute ‘cut-off’ value for renal function below which ICCM cannot be administered – every administration is a balance of perceived risk for the patient versus the benefit of the procedure, and this is a clinical judgment. Emergency procedures, such as CT perfusion for acute stroke, should never be delayed while waiting for kidney function test results, even in patients who are known to have poor kidney function or diabetes.
7. Do you have thyroid disease, thyroid cancer, or have you recently been treated for thyroid cancer?
   The iodine load in the ICCM might exacerbate or induce an episode of thyrotoxicosis. Free iodine in ICCM can compete with radioactive iodine when treating thyroid cancer.
8. Do you have myasthenia gravis or sickle cell disease?
   Worsened symptoms (muscle weakness in the former and pain related to bone marrow disease in the latter) have occasionally been reported, and patients need to be advised about this before ICCM. These conditions are not contraindications to ICCM.
9. Are you pregnant?
   This is not a contraindication to ICCM, but the medical imaging practice always needs to be advised about this for any procedure, especially if the patient’s abdomen is to be exposed to the primary X-ray beam as part of the procedure.

What are the absolute contraindications for an ICCM injection?

There are no absolute contraindications. For each patient, the risks of ICCM administration by any route must be weighed against the perceived clinical benefit to the patient of the diagnostic or therapeutic procedure. See risk factor discussion above.

What are the relative contraindications for ICCM injection?

• Severe renal impairment, where the benefits of the ICCM administration do not outweigh the small risk of CI-AKI. However, there are risks to withholding ICCM, such as reduced diagnostic accuracy, and these need to be considered in weighing risk versus benefit. Discussion with a radiologist can help to clarify the risk–benefit balance and other possible diagnostic strategies that might obviate the need for ICCM in patients with severe renal impairment.
• Active, untreated thyrotoxicosis is a relative contraindication to ICCM if the procedure is not a medical emergency.
• Active myasthenia gravis – patients should be advised about the small risk of a temporary worsening of symptoms.

Asthma, multiple allergies, severe (eGFR <30 mL/min) renal function impairment and current hyperthyroidism (clinical or biochemical) increase the risk of ICCM administration. Beta-blockade can reduce or eliminate the effectiveness of adrenaline in the event of an anaphylactic reaction.

These relative contraindications to ICCM administration need to be notified to the medical imaging practice/hospital because of the increased risk for the patient and to identify the patient as potentially requiring additional preparation or monitoring after ICCM administration.

What are the adverse effects of an ICCM injection?

Immediate:

Allergic-type/anaphylactic reactions occur in less than 3% of patients. These almost always occur within minutes to 1 hour after administration of ICCM given intravenously or intra-arterially, and are less common after ICCM given by other routes (orally or intra-articularly, for example). Mild reactions (itching, a mild rash, sneezing or vomiting) require no treatment or antihistamines only. Moderate reactions can occur in 1 in 3000 people, and present with generalised rash and anaphylactic oedema. This requires intravenous adrenaline and steroids. Severe reactions occur in 1 in 25,000 patients, requiring adrenaline administration and hospital admission. Approximately 1 in 170,000 people die after a severe anaphylactic reaction that fails to respond to medical treatment.

Extravasation of ICCM at the injection site is usually minor and treated with warm or cold compresses as soon as it is noted. Simple analgesia is usually all that is required in the following few days and symptoms usually settle promptly. Increasing swelling and pain at the injection site or limb paraesthesias are rare and usually the result of major extravasation. They might indicate thrombophlebitis and/or compartment syndrome, and require emergency medical treatment.

Aspiration of orally administered ICCM is a risk for patients with altered conscious state and/or impaired gastric emptying for any reason. Aspiration of Gastrografin can produce acute pulmonary edema. Non-ionic ICCM (iopamidol, for example) is often given instead of Gastrografin in this situation, as it is not associated with pulmonary oedema in the event of aspiration.

Delayed (hours to weeks post-ICCM administration):

Decrement in renal function, usually temporary and asymptomatic, is seen in some patients with pre-existing chronic severe or acutely deteriorating renal function (AKI) before ICCM, particularly if they have large volumes of ICCM given intra-arterially or receive multiple ICCM doses over a few hours or days. The only intervention that has been shown to reduce the incidence of AKI after ICCM in such ‘at risk’ patients is intravenous normal saline administered for a few hours before and after ICCM. Administration regimes vary, but 1–2 L of N saline for 4 hours before and 4 hours after ICCM is a typical protocol. This might be modified based on the patient’s cardiac function in order to avoid any worsening or potential precipitation of heart failure. There is no conclusive evidence that the addition of bicarbonate or N–acetyl cysteine to this protocol results in further reduction in the incidence of AKI.

Delayed allergic-type reactions can occur up to 1 week after ICCM, and include salivary gland swelling, jaw or joint pain, skin rash/pruritus or facial swelling. They are almost never reactions of the moderate or severe type that occur within minutes after ICCM administration.

Hyperthyroidism is an uncommon, but recognised, delayed complication of ICCM, and typically occurs 2–8 weeks after ICCM administered intravenously or intra-arterially in patients who have clinical, biochemical hyperthyroidism, an autonomous hyperfunctioning thyroid nodule or less commonly euthyroid patients with a multinodular goitre. This generally responds to conventional medical treatment for the condition.

Rarely, hypothyroidism can be a late complication of ICCM administration, but hyperthyroidism is much more common.

For patients who have thyroid cancer and are to have radioactive iodine treatment, the iodine in ICCM will block uptake of radioactive iodine into primary and metastatic thyroid cancer for up to 8 weeks after ICCM administration. Therefore, patients who are planned for radioactive iodine treatment should not be given ICCM before radioactive iodine treatment unless the benefits outweigh the risks of delaying their thyroid cancer treatment. This might include situations such as patients with thyroid cancer who require emergency coronary angiography, CT perfusion for acute stroke, or CT angiography of the chest or abdomen in the setting of major trauma or suspected aortic dissection.
Lactic acidosis in patients taking metformin-containing medication is rarely seen. It occurs in patients with severely reduced renal function or acute kidney injury, and is a drug-related side effect rather than being precipitated by ICCM.

Is there any specific post procedural care required following an ICCM injection?

Pre- and post-procedural hydration with intravenous normal saline is indicated in patients with chronic stable severe renal impairment (eGFR <30 mL/min) if it is anticipated that they will receive a large volume of contrast over a period of hours to a couple of days as a result of one or more imaging procedures.

Cessation of metformin from the time of ICCM administration is recommended if the patient has acutely deteriorating renal function or chronic severe renal impairment (eGFR <30 mL/min). After 48 hours, renal function should be re-tested before metformin being recommenced if eGFR is acceptable. It is not necessary for metformin to be ceased in patients who have stable renal function with eGFR greater than 30 mL/min, as the risk of lactic acidosis due to post-ICCM renal function deterioration is considered to be extremely low to non-existent.

Are there alternatives to ICCM?

Non-contrast imaging might be appropriate depending on the clinical indication. Ultrasound or magnetic resonance imaging might also be appropriate alternatives. Contrast might be indicated with magnetic resonance imaging, but this contains gadolinium rather than iodine (See InsideRadiology: Gadolinium Contrast).

Further information about ICCM:

The relatively small risks associated with ICCM must be weighed against the considerable benefits to diagnosis in some situations. Risk assessment of your patient for contrast-induced renal impairment allows patients at increased risk to have renal function testing before they make their appointment. Not everyone needs renal function testing: if your patient has no risk factors on questioning, there is no reason to carry out renal function testing.

It is critical that you provide detailed information about the patient’s signs/symptoms and your clinical question on the referral for CT scanning, as this will strongly influence the radiologist’s decision to give ICCM or not. This in turn will influence whether the appropriate scanning technique is carried out to answer the question. CT scanning can be carried out in many different ways depending on the reason for the scan, so accurate information and, in particular, your main clinical questions need to be provided in the referral information.

Useful websites about ICCM injections:

• ACR Manual on Contrast Media, version 6, 2008: clinical-mri.com/wp-content/uploads/textbooks/media_updates/contrast_manual_ACR_for_web.pdf
• RANZCR Iodinated Contrast Guidelines: www.ranzcr.edu.au/quality-a-safety/radiology/iodinated-contrast-media-guideline

*The author has no conflict of interest with this topic.

Page last modified on 26/7/2017.