What is Contrast Agent Toxicity?
Contrast agents or contrast media are substances that enhance the visibility of particular tissues in medical imaging by changing how they interact with electromagnetic radiation or ultrasound waves. These agents can be given to a patient by mouth, rectum, or through a vein, depending on the exact type of imaging being done.
For x-rays or CT scans, contrast agents usually contain iodine or barium. Iodine agents can vary greatly in how much they influence the imaging process, largely dependent on the amount of iodine they contain. These agents are most commonly injected into the veins, but rapidly move out of the bloodstream due to their molecules being small enough to leak through capillary walls. They can also be administered orally or rectally to improve the quality of images of the stomach and intestines.
Barium sulfate is often used when imaging the digestive system. Typically, a patient takes it orally or via an enema as it’s mixed into a liquid to create a suspension.
For MRIs, most contrast agents contain a metal called gadolinium. Unlike the agents used in x-rays, these agents work by shortening the time it takes for water molecules to align with the magnetic field created by the imaging machine, enhancing the brightness of the tissues being scanned. These agents are designed to stay in the bloodstream longer than those used for x-rays.
Ultrasound imaging makes less frequent use of contrast agents, but when they are used, they consist mostly of tiny gas-filled bubbles, similar in size to red blood cells, and are introduced into the patient’s body through a vein.
The use of contrast agents is widespread in current medical practice. However, as their use has grown, so has concern for the potential harm they could cause.
What Causes Contrast Agent Toxicity?
Contrast toxicity is a condition where substances used to enhance medical images – iodine, barium, gadolinium, or microbubbles – have a damaging effect on the body’s tissues. This can happen when a patient’s health background isn’t fully known, especially if they have allergies, heart conditions, or kidney disease. There are also certain groups of people, including pregnant women, breastfeeding women, and those taking the drug metformin, who are more likely to be at risk from the harmful effects of these substances. Radiologists, who often don’t know the patient’s history well, have to depend on the referring doctor’s opinion or a quick consent process to determine the suitability of the requested procedure.
There’s also an extra risk of contrast toxicity when these substances are used in ways that are not explicitly approved by health authorities. In the United States, the Food and Drug Administration (FDA) only approves a specific list of contrast agents for particular uses in certain parts of the body. However, because the FDA hasn’t been able to test every possible combination of contrast agents, patient groups, and uses, doctors sometimes have to use these substances off-label – that is, in a way that hasn’t been evaluated by the FDA. In particular, needs in MR angiography, heart, and child patient groups are frequent instances where off-label use is needed.
Lastly, even if a person doesn’t have a previous health history and their type of imaging has received FDA approval, they might still experience contrast toxicity. This is because the contrast agents are foreign substances which can interact in unpredictable ways with the body’s tissues. Simply put, contrast toxicity can happen to any person exposed to a contrast agent, regardless of the circumstances.
Risk Factors and Frequency for Contrast Agent Toxicity
When using contrast agents for medical procedures, one of the main adverse effects that can occur is a condition called contrast-induced nephropathy (CIN). This refers to a quick decline in kidney function that happens between 24 to 48 hours after exposure to the contrast agent. CIN is defined more by symptoms than by specific lab values, but it is often suspected if, within 48 hours of being exposed to an iodinated contrast agent, a patient shows:
- An increase in serum creatinine of more than 25% from baseline
- An increase in serum creatinine of 0.3 to 0.5 mg/dL
- A drop in urine output to less than 0.5 mL/kg per hour for a period exceeding 6 hours
Studies suggest that CIN might account for up to 10% of kidney failures acquired in hospitals. It is ranked as the third most common cause of new acute kidney failure in inpatients. However, newer research including large studies with up to 54,000 patients points to a lower incidence rate of CIN than what was initially thought.
It’s interesting to note that CIN has only been seen in cases where radiography contrast agents are used. Gadolinium-based contrast agents, commonly used for MRIs, do not seem to cause CIN. They have been linked to nephrogenic systemic fibrosis (NSF), a chronic condition characterized by hardening of the skin, which seems to be particularly seen in patients with pre-existing renal disease. However, the exact mechanism of NSF remains unknown.
When we look at other adverse reactions beyond CIN, they usually get categorized as allergic-like or physiologic reactions. Historically, the use of high osmolar agents could cause an adverse reaction in up to 15% of patients. However, newer low osmolar agents have significantly decreased this rate to between 0.2% to 0.7%. Gadolinium contrast material, often used in MRI, has an even lower adverse effect rate.
Surprisingly, most adverse reactions are minor, with about 90% of them being nausea, vomiting, or a mild rash that can be managed with just observation and diphenhydramine. A common misconception is that people who have shellfish allergies are more prone to having adverse reactions to contrast agents. However, recent data has debunked this myth. The American College of Radiology states there is no scientific evidence to suggest questioning a patient about shellfish allergies before administering contrast agents.
Signs and Symptoms of Contrast Agent Toxicity
People who experience toxicity related to contrast agents (used in certain medical tests) can show a wide variety of symptoms. However, all these individuals have had exposure to a contrast agent within the previous 72 hours.
Contrast-induced nephropathy (CIN) might show up as a temporary increase in creatinine levels in the blood, possibly along with low urine output. Passing the diagnosis of CIN requires a subsequent decrease in creatinine levels measured within 2 to 3 days. There are several recognized risk factors for developing CIN, such as chronic kidney disease, diabetes, dehydration, use of diuretics, being older, and exposure to other drugs or diseases that affect how blood flows within the kidneys.
The Roxana Mehran score is used to predict a patient’s risk of developing CIN based on various factors:
- Age (4 points if older than 75 years)
- Anemia (3 points)
- Diabetes (3 points)
- Congestive heart failure (5 points)
- Use of an intra-aortic balloon pump (5 points)
- An eGFR between 60 and 40 (2 points)
- An eGFR between 40 and 20 (4 points)
- An eGFR below 20 (6 points)
- Low blood pressure requiring medicine to increase it (5 points)
- Volume of contrast media used (1 point per 100ml)
A score of fewer than 6 points indicates a minimal risk (of 7.5%) for developing CIN while a score of more than 16 points indicates a top risk of 57%.
Negative reactions to contrast agents can be categorized as either allergic-like, such as nausea, vomiting, hives, difficulty breathing, swelling and other similar symptoms, or as physiological, which can result in abnormal heartbeat, decreased heart pumping capability, fluid build-up in the lungs, and seizures.
People with certain pre-existing conditions may be more likely to experience particular adverse events. For example, patients with chronic obstructive pulmonary disease (COPD) or asthma have a higher likelihood of experiencing difficulty breathing. Those with a history of heart disease are more likely to have changes in their blood flow, and patients with myasthenia gravis might see a significant worsening of their disease symptoms within 24 hours of receiving the contrast agent.
The biggest risk factor for experiencing negative effects from a contrast agent seems to be a previous history of negative reactions to contrast agents.
Testing for Contrast Agent Toxicity
It’s common to measure BUN (Blood Urea Nitrogen) and creatinine levels in your blood before using contrast agents. These tests give doctors an idea of how well your kidneys are working, so they can make accurate comparisons in the future. Keeping track of a patient’s vital signs, like heart rate and blood pressure, before and during the use of contrast agents, can also help in identifying any harmful effects.
Changes in blood pressure, either being too high or too low, might happen due to heart-related or allergic reactions to the contrast agent. However, there aren’t any standard tests that can determine toxicity from contrast agents. Since the signs of toxicity can vary widely, doctors mainly rely on detailed patient history and physical exams to pick up on any harmful effects, especially if you’ve been exposed to a contrast agent recently.
Treatment Options for Contrast Agent Toxicity
If patients have an immediate allergic reaction to contrast dye, the administration of the dye should be stopped right away, if possible. Hydrating the patient and giving antihistamine treatment are the next steps. While there isn’t a specific drug regimen that is universally followed, treatments often include intravenous fluids, diphenhydramine, and hydrocortisone. For severe reactions, adrenaline may also be used.
Patients with a history of allergic reactions can sometimes receive preventive medications, which may include prednisone, hydrocortisone, or diphenhydramine. A review of several studies indicates that using preventive medicines can somewhat reduce the risk of mild symptoms like respiratory distress or blood pressure issues. However, it does not seem to lower the risk of more serious reactions.
For patients with Contrast-Induced Nephropathy (CIN), which is a type of kidney damage, the treatment options are not very clear. Some treatments like acetylcysteine, a compound called fenoldopam, and rehydration have shown minimal effects in clinical trials. Mainly, doctors manage CIN by keeping the patient hydrated, monitoring kidney functionality closely, and providing supportive care.
What else can Contrast Agent Toxicity be?
Contrast toxicity is a medical condition that could be mistaken for other health issues. This could occur at the same time, or be confused with:
- Kidney problems or sudden kidney failure
This could happen either because of contrast exposure or before it. Regardless, there may be increased creatinine or changes in the levels of blood urea nitrogen. - Heart failure
- High blood pressure in the lungs
This could be because of contrast exposure or due to existing heart problems. Both might show similar signs of right heart overload. - Severe allergic reactions
The skin rashes and feeling of nausea that might happen due to an allergic reaction to contrast agents may also be caused by exposure to another substance. Therefore, any new exposure must be considered when patients show such symptoms.
What to expect with Contrast Agent Toxicity
The outlook for contrast toxicity is generally good, with serious side effects happening less than 1% of the time. It was once thought that Contrast-Induced Nephropathy (CIN) occurred about 10% of the time, but recent comprehensive reviews of multiple studies have questioned this number. Generally, the benefits of using contrast agents for diagnostic purposes are believed to significantly outweigh the rare occurrence of toxicity.
Possible Complications When Diagnosed with Contrast Agent Toxicity
The side effects of contrast toxicity can range from minor symptoms to extremely rare but potentially fatal reactions. Unfortunately, there is limited knowledge on these complications and more studies are needed to fully understand all possible risks involved with contrast toxicity.
Possible side effects include:
- Kidney malfunction
- Heart-related events
- Anxiety
- Severe sickle cell crises
- Worsening of myasthenia gravis (a chronic autoimmune neuromuscular disease) symptoms
- Thyrotoxicosis (an excessive amount of thyroid hormones in the body)
- Vasospasm (the constriction of blood vessels)
Preventing Contrast Agent Toxicity
Preventing issues that may arise from the use of contrast in medical tests is a unique process for each person, since the chance of having a bad reaction is quite low, but the advantage of getting a faster, more accurate diagnosis is significantly high. A comprehensive talk about the risks, benefits and alternatives of using contrast agents could be held before they are used on a patient. Although it’s currently not required to give formal approval for the use of contrast agents, informing patients more about this could help them be ready and prevent them facing any negative outcomes related to the use of contrast in tests.
