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Adverse Reactions to Contrast Agents: Dispelling the Myths

3.00 Contact Hours
A score of 80% correct answers on a test is required to successfully complete any course and attain a certificate of completion.
Author:    Berthina Coleman (MD, BSN,RN)

Outcomes

The purpose of this course to enable the participant to fully understand the pathophysiology and management of allergic reactions to contrast agents. They will be able to define the different types of allergic reactions. This course will also help clarify some myths that have been perpetuated in the medical community regarding allergic reactions to contrast agents specifically as it pertains to shellfish allergies.

Objectives

By the end of this activity, the participant will be able to:

  1. Define the purpose of contrast agents
  2. Name the two main categories of iodinated contrast agents
  3. Discuss the risk factors associated with adverse reactions to contrast agents
  4. Compare the two types of allergic reactions to contrast agents
  5. Define contrast-induced nephropathy
  6. Discuss the clinical manifestations associated with nephrogenic systemic fibrosis
  7. Discuss the treatment regimen for nephrogenic systemic fibrosis
  8. Explain the recommendations for administering contrast agents in patients taking Metformin
  9. Recognize whether a shellfish allergy is related to iodinated contrast agent
  10. Discuss contrast agent use in breastfeeding women

The purpose of contrast agents

Contrast agents are commonly used with all types of imaging modalities including Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Ultrasonography (US) and Fluoroscopy. Although their use significantly enhances the diagnostic information of each of these tests, there are also potential risks from the administration of contrast agents that should be considered. Therefore, prior to their administration providers must consider the potential risks associated with the respective contrast agents.

The risk of adverse reactions from iodinated contrast agents used in imaging is well established. The exact etiology of contrast reactions after administration of intravascular iodinated contrast agents is not well known. The average incidence of allergic reactions for nonionic formulations is approximately 3% or less. The assumption is that the incidence for ionic contrast agents is higher than nonionic contrast agents.

Types of Iodinated Contrast Agents

Contrast agents can be administered by mouth, intravenously, per rectum, intrathecally (into the epidural space), intravesical (bladder), or into joint spaces (arthrograms). Being able to administer these contrast agents in so many ways and orifices (be they natural or iatrogenic) allows radiologists and other clinicians to enhance the differences between tissues that would normally be very close in attenuation. In the world of imaging today, the use of contrast is ubiquitous for most imaging modalities especially CT imaging.

The primary routes of delivery for CT are intravenous and enteric that is oral and rectal. Intravascularly administered agents are iodinated material that moves quickly into the extracellular fluid. No significant metabolism or transformation occurs. Excretion is primarily through the kidneys. In patients with compromised renal function, there is greater excretion through the biliary system and gastrointestinal tract.

Intravascular contrast agents

Usually, water-soluble contrast agents are used intravenously in CT imaging for better visualization of vascular structures and hypervascular tissues.  First generation contrast agents are high osmolar compounds with an osmolality up to 5 to 8 times the osmolality of blood. When used intravenously, these agents are associated with intravascular volume overload due to their high osmolality which proved problematic for patients with heart failure. They are also associated with more reports of pain when administered intravenously. Currently, the only use for high osmolality agents is for gastrointestinal or retrograde urological procedures such as cystography. Also, they are advantageous because of their low cost.  An example is Isopaque.

Low osmolality nonionic compounds are associated with fewer adverse reactions when administered intravenously. Examples include Omnipaque and Isovue. Nonionic iso-osmolar agents such as Visipaque are hydrophilic. They are usually used in patients at increased risk for contrast-induced nephrotoxicity.

Gastrointestinal Agents

Barium Sulfate mixtures are used to opacify the bowel loops. The contrast agent is administered orally about 1.5 to 2 hours prior to imaging to allow for appropriate transit within the bowel. If bowel perforation is suspected, water soluble iodinated agents are recommended. High-osmolality iodinated contrast agents should be avoided in patients who are at risk for aspiration. Aspirated high-osmolality contrast agents can cause chemical pneumonitis with associated pulmonary edema. Aspiration of large volumes of both barium-based and iodinated oral contrast agents have rarely been reported as fatal.

Volumen is an ultra-low concentration barium sulfate agent which contains sorbitol-a sugar alcohol known to promote gastrointestinal distention. Volumen proves particularly useful for CT enterography. Volumen is useful in that it provides negative enteric contrast filling the bowel with a low attenuation fluid. This allows for better evaluation of bowel wall thickening or abnormal enhancement when used in conjunction intravenous agents.

Risk Factors for Adverse Intravenous Contrast Material Reactions

Ordering providers are encouraged to review the following factors prior to the administration of contrast agents. Nurses and technician play a critical role by verifying whether these factors have actually been reviewed before the patient leaves for the study or exam. Although it is the ordering provider’s responsibility to ensure that the patient’s history is thoroughly reviewed, each member of the clinical team should be aware of these factors and must be encouraged to speak up if they feel something is being overlooked by the rest of the team.

History of prior allergic reactions

It is common knowledge that any history of allergic reactions predisposes individuals to allergic reactions to other substances. A history of allergic reactions is sometimes challenging to evaluate in clinical practice because the definition of allergy reactions is not as clear to a patient reporting them. For example, a minor allergy such as seasonal rhinitis is very common, but the patients do not necessarily experience typical “allergic reactions.”

It is well documented that a prior allergy-like reaction to contrast media increases the risk of a subsequent reaction by up to 5-fold.  If the patient reports a history of allergies, the providers and other clinical staff should focus specifically on the type of reaction including the specific agents and the experienced symptoms. The goal here is to establish the severity of the “allergy reaction” to distinctly identify patients who may be atopic.

Atopy is defined as a genetically determined inclination to produce specific immunoglobulin E (IgE) following exposure to specific allergens. Once this occurs, the patient is sensitized, but it is important to note that sensitization does not imply that the host exposed is allergic to that specific allergen. Individuals sometimes produce IgE to allergens in a given substance but never go on to develop symptoms upon subsequent exposure to that substance. It is not fully understood why certain individuals develop active allergic disease while others are only sensitized (Baig, 2014).

Asthma

A history of asthma may confer an increased risk of developing an allergic reaction to contrast agents because these patients also have a history of other atopy-related conditions.

Risk factors pertaining to renal insufficiency

Renal insufficiency prior to the administration of iodinated contrast increases the risk of Contrast Induced nephrotoxicity (CIN) and Nephrogenic Systemic Fibrosis (NSF).  Patients with acute renal failure, as well as End Stage Renal Disease, are included in this group.

Cardiovascular Disease

Patients with cardiovascular disease such as angina, congestive heart failure, severe aortic stenosis, primary pulmonary hypertension, or cardiomyopathy are at risk for adverse reactions to contrast agents. In this group of patients, the volume of contrast and the osmolality of the contrast agents administered are critical because these two factors affect the cardiovascular status significantly.

Anxiety

There are a few studies which have shown that the patient’s emotional state can affect the occurrence of adverse effects to contrast agents.

Paraproteinemia

Paraproteinemias, especially multiple myeloma, predispose patients to irreversible renal failure after the administration of high osmolality contrast agents.  There is no available data to support an increased risk when administering low osmolality or iso-osmolality agents. 

Age

Infants and neonates are at increased risk for adverse effects of contrast agents. Contrast volume is an important consideration because of the low blood volume of the patients in this group. Low blood volume makes them at increased risk for hyperosmolality with its associated cardiotoxic effects.

Types of Contrast Reactions

Allergic-Type Reactions

There are three types of contrast allergic reactions: Minor cutaneous and mucosal manifestations, Smooth muscle and minor anaphylactoid responses and lastly major cardiovascular and anaphylactic responses. These reactions can either occur acutely or can be delayed for up to 1 week after the administration of contrast agents.

Acute Reactions

Acute reactions are characterized as allergic-type reactions; they are not dose related and are of unclear etiology. These reactions include nausea, vomiting, flushing, headache, dizziness, anxiety, hypertension, cardiac arrhythmias, cardiogenic pulmonary edema, vasovagal reactions, and rarely seizures. It is important to note that premedication is less helpful in avoiding allergic reactions.

Mild allergic-like reactions most frequently occur while the patient has the examination. Acute bronchospasm, profound hypotension, and severe urticaria may occur during or within minutes of the administration of contrast material.

Moderate signs and symptoms of contrast reaction include tachycardia or bradycardia, hypertension, generalized erythema, dyspnea, wheezing, bronchospasm, laryngeal edema, and hypotension. The clinical findings usually require immediate treatment and observation in case the symptoms progress to life-threatening ones.

Severe signs and symptoms of contrast reaction are often life-threatening and include severe laryngeal edema, convulsions, unresponsiveness, cardiopulmonary arrest, profound hypotension, and cardiac arrhythmias, necessitating immediate recognition and aggressive treatment. It is recommended that patients who have had such reactions should not receive iodine contrast agents ever again even after receiving pretreatment.

Delayed Reactions

Delayed adverse reactions typically occur 30 minutes to 1 week or more after the administration of contrast material. Delayed reactions are more likely following the administration of an ionic contrast agent than a nonionic contrast agent. The typical symptoms of delayed reactions involve urticaria or pruritus and are treated with antihistamines or topical steroids.

Contrast Induced Nephropathy

Contrast Induced Nephropathy (CIN) is defined as Acute Kidney Injury which occurs within 24-48 hours after the administration of contrast agents. It is important to note that other causes of Acute Kidney Injury (AKI) must be excluded prior to diagnosing CIN. Acute Kidney Injury (AKI) is defined as an absolute increase in the serum creatinine of 0.5mg/dl or relative increase by 25% from the baseline. The risk of CIN is very low in a patient with normal renal function (that is, a glomerular filtration rate greater than 60 ml/min).  In general, CIN is self-limiting, and the renal function should return to baseline within 7 -10 days without progressing on to chronic renal failure.

On the other hand, if a patient has an abnormal renal function at baseline, that is a GFR less than 60, then the risk of CIN is much higher especially in elderly patients with diabetes. In these patient groups, traditionally what has been done is appropriate screening with subsequent hydration before and after contrast administration.

Gadolinium based contrast agents

Mild reactions from gadolinium based agents typically occur in about 1% of all patients. Severe and anaphylactic reactions to gadolinium based contrast are extremely rare. All gadolinium based contrast agents are chelated with the intention of making the agents less toxic or non-toxic while also allowing for renal excretion.

Nephrogenic Systemic Fibrosis

Gadolinium was first discovered in 1880 and named after Johan Golin. Gadolinium has seven unpaired electrons making it one of the strongest paramagnetic atoms on the periodic table. Consequently, even when gadolinium is bound is bound to a chelator, the unpaired electrons are still available for interaction with other protons and nuclei to facilitate the longitudinal relaxation times (T1 property) and also influencing the transverse relaxation time which is a T2 property.

The first known case of nephrogenic systemic fibrosis occurred in 1997 after the administration of high doses in patients with renal failure had become the standard of practice. At the time of the initial diagnosis, nephrogenic systemic fibrosis was previously called nephrogenic fibrosing dermopathy. It was named based on the primary dermatologic manifestations which were initially noticed. Once the involvement of internal organs was noted, the name was changed to nephrogenic systemic fibrosis.

The cause of nephrogenic systemic fibrosis was discovered in 2006 by a Danish Nephrologist Grobner who noted that 5 out of 9 patients with renal failure who had gadolinium enhanced MR imaging were subsequently diagnosed with nephrogenic systemic fibrosis.

In cases where the patient gets exposed to the non-chelated component of gadolinium contrast agent, there has been an association with a nephrogenic systemic fibrosis. In the past, gadolinium contrast agents were administered in high doses for MR imaging including in patients with acute renal failure or patients on dialysis. In the early 2000’s, the association between contrast administration and nephrogenic systemic fibrosis was established thereby prompting clinicians to start administering low doses of contrast agents especially in patients undergoing dialysis or patients with a GFR < 30 ml/hr. High doses are very rare nowadays with most applications being adjusted to a standard dose of 0.1mmol/kg.

Regulatory authorities both in the US and in Europe have issued a black-box warning for all gadolinium based contrast agents. They have also issued a cautionary warning to patients with acute or chronic renal dysfunction, patients with a GFR < 30 ml/min, patients with acute renal failure secondary to hepatorenal syndrome or patients who are in the perioperative period for liver transplantation.

When gadolinium-based contrast agents are administered in patients undergoing dialysis, the recommendation is that the administration of these agents should be scheduled just before the next dialysis treatment to facilitate quick clearance from the patient’s system.

Nephrogenic systemic fibrosis is a condition which patients on dialysis or patients with profound renal failure are affected by the administration of gadolinium based contrast. It is a rare fibrosing condition whose clinical manifestations include; skin thickening, thickened underlying connective tissue leading to contractures and thereby decreased range of motion. Occasionally, the process of fibrosis can extend to involve the heart, muscles and the lungs with debilitating consequences. An overwhelming majority of nephrogenic systemic fibrosis cases are mild and remain limited to dermatologic conditions. However, up to 5% of cases progress to severe manifestations of the condition, and some cases take a fulminant course leading to death.

There are very limited treatment options for nephrogenic systemic fibrosis. Therefore, prevention is important. As such exposure of gadolinium based contrast agents is limited in patient groups who are at increased risk for developing nephrogenic systemic fibrosis including diabetics, patients on dialysis or patients with severe renal failure (GFR less than 30ml/min).

In patients already on dialysis, the current recommendation is prompt dialysis following the performance of a contrast enhanced MR study using gadolinium based contrast agents. In patients who are at risk for nephrogenic systemic fibrosis, alternate diagnostic procedures using different modalities should be considered, or MR imaging without the use of gadolinium based contrast agents should be performed.

Specific Risk factors for Nephrogenic Systemic Fibrosis

Renal failure

Note that Nephrogenic Systemic Fibrosis is usually diagnosed in patients with severe renal dysfunction especially patients undergoing dialysis or approaching the stage of needing dialysis, hence the use of the term nephrogenic in nephrogenic systemic fibrosis. The GFR is usually calculated based on the age, gender, ethnicity and the serum creatinine. It is not recommended to perform MR imaging with gadolinium based contrast agents in patients with acute renal failure with rising creatinine levels. These individuals should be scheduled for gadolinium based contrast agents enhanced MR once the creatinine levels start to decrease.

Dialysis

Originally, it was believed that dialysis was a risk factor for nephrogenic systemic fibrosis given that up to 80% of the patients diagnosed were on dialysis at the time of diagnosis. However, it seems that some of these patients received gadolinium based contrast agents prior to the time dialysis was initiated. However, at the time of dialysis, the renal failure was so severe that the patients necessitated dialysis and therefore an erroneous connection was made between the two. The fact that dialysis therapy was necessary at the time of dialysis only underscores the severe renal dysfunction associated with nephrogenic systemic fibrosis.

As previously mentioned, the current recommendations are that dialysis should be performed  within 24 hours of gadolinium based contrast agent administration in patients with end-stage renal disease.  Prince et al. (2008) reported that performing dialysis the day after the administration of gadolinium based contrast agents has a protective effect.

Gadolinium based contrast agent dose

It has been reported that the use of high doses of gadolinium based contrast agents and possibly the use of linear nonionic gadolinium based contrast agents both increase the risk of nephrogenic systemic fibrosis.

Broome et al. (2007) conducted a study and noted that 0/94 patients receiving the standard dose of 0.1mmol/kg of a nonlinear contrast agent developed nephrogenic systemic fibrosis. However, 12 out of 207 patients who received high doses of the same contrast agent developed nephrogenic systemic fibrosis. There are multiple other studies which have implicated the use of high doses of gadolinium based contrast agents as an independent risk factor for nephrogenic systemic fibrosis.

Gadolinium based contrast agent type

There are significant differences between macrocyclic and linear agents as well as between ionic and nonionic linear agents. Linear agents are simpler and generally less expensive to synthesize compared to macrocyclic agents. Macrocyclic agents are different from linear agents in that they have greater kinetic stability due to the complete encircling of the gadolinium (Gd) ion with covalent bonds. This covalent bond makes it very difficult for Gd ions to be released into the tissue, even when there is delayed excretion. This supports the idea that macrocyclic agents are almost completely safe and practically free of risk of nephrogenic systemic fibrosis.

Although nonionic agents have a far lower incidence of allergic reactions compared to ionic agents, they are less stable once injected compared to ionic agents. This makes the nonionic linear more likely to be associated with nephrogenic systemic fibrosis.

Proinflammatory Events

Sadowski et al. (2007) noticed that all the cases of nephrogenic systemic fibrosis were occurring in patients who were sick in-patients. In their report, no cases of nephrogenic systemic fibrosis were found in outpatients. All the patients diagnosed with nephrogenic systemic fibrosis had underlying proinflammatory conditions such as recent major surgery or infection. The theory is that proinflammatory states are marked by high levels of circulating fibrocytes which are attracted to gadolinium deposited in tissues. Additionally, proinflammatory conditions are associated with edema, which increases the fluid in the interstitial compartment thereby increasing the chances of nephrogenic systemic fibrosis.

Hyperphosphatemia

When phosphates bind to a gadolinium ion, the bond is irreversible with preventing the gadolinium ion from rapidly reassociating with the chelator. Once the Gd irreversibly binds to phosphates and precipitates out of solution into tissues, the unidirectional reaction releasing gadolinium from the chelator continues to be propagated. Prince et al. (2009) reported a higher incidence of Nephrogenic Systemic Fibrosis in patients with hyperphosphatemia.

Clinical Manifestations of Nephrogenic Systemic Fibrosis

Radiologists rarely encounter Nephrogenic Systemic Fibrosis because unlike other contrast reactions it does not occur at the time of the imaging study. Rather it occurs several weeks to months later. The lesions of Nephrogenic Systemic Fibrosis usually involve the dermis in the extremities, symmetrically, and less frequently it will affect the trunk.

The course of Nephrogenic Systemic Fibrosis is usually more-indolent with several weeks to months of symptoms before the diagnosis is made. Less often the disease adopts a fulminant course leading to rapid death on occasion. The primary lesions of Nephrogenic Systemic Fibrosis are firm to hard skin-colored or erythematous papules which may coalesce to involve large areas of the trunk or the extremities. Occasionally they have been described as thickened brawny indurations which look like the peau d’orange lesion or have a cobblestoned appearance.

As the disease progresses, the skin will progressively harden and become tethered. Joint contractures may develop when the fibrosis crosses through the joint thus severely impairing physical function and movement.

Patients afflicted with Nephrogenic Systemic Fibrosis usually complain of severe extremity pain, pruritus, skin tightness, or a burning sensation.

Radiologic Manifestations of Nephrogenic Systemic Fibrosis

There are a variety of radiologic findings such as diffuse soft-tissue tracer uptake on bone scans, skin thickening and subcutaneous stranding on mammographic, CT and US imaging. Increased FDG (fluoro-2-deoxy-D-glucose) uptake in the skin and muscles on positron emission tomographic imaging.

Histologic Findings with Nephrogenic Systemic Fibrosis

Given the involvement of the subcutaneous tissues and underlying muscle in Nephrogenic Systemic Fibrosis, a deep dermal biopsy is necessary to confirm the diagnosis histologically. The histologic findings noted upon biopsy are usually nonspecific inflammatory changes which only serve to confirm a clinical diagnosis. The combination of clinical features and biopsy findings are necessary for a definitive diagnosis.

Treatment of Nephrogenic Systemic Fibrosis

There is no therapy which works effectively on a consistent basis for Nephrogenic Systemic Fibrosis. It remains, however, clear that improving renal dysfunction from any cause appears to slow or arrest the progression of the disease. Multiple authors have reported circumstances of cure or a reduction of symptoms after renal transplantation or recovery from an episode of acute renal failure (Grobner, 2006; Weigel & Broome, 2008; Marckmann et al., 2006).

Given the propensity of contractures to occur with Nephrogenic Systemic Fibrosis, physical therapy should be started early to maintain and improve the range of motion in the joints. Other therapies such as extracorporeal photopheresis, plasmapheresis, immunoglobulin therapy, steroids and immunosuppressive therapies have been used.

Management of Contrast Reactions

Allergic Type Reactions

Pretesting patients for potential major adverse reactions has been shown to be of no value in determining who will have an adverse reaction. Nonionic contrast media has mostly replaced ionic contrast media for most clinical practices in order to minimize the chance of allergic and other adverse contrast reactions.

Patients reporting allergic reactions to contrast media should be premedicated with prednisone and diphenhydramine. The prednisone is usually administered orally the night before and the morning of administration as well as oral diphenhydramine.

Pretreatment with corticosteroids is noted to be useful in reducing all types of contrast reactions except those predominantly characterized by hives. However, it is important to note that premedication may not prevent the occurrence of adverse reactions completely.

Treatment with H2 receptor blockers has not been shown to be valuable in preventing allergic reactions to contrast. However, the pretreatment of patients with known prior anaphylactic reactions to contrast with H1 receptors has been shown to be effective.

Contrast Induced Nephropathy

Interventions to prevent contrast nephropathy include pre and post hydration and the maintenance of increased urine output or flow which is usually greater than 200 mL/h. Some studies have shown N-acetylcysteine administration prior to intravenous contrast administration has been shown to reduce contrast induced nephropathy (King, 2011).

Patients at increased risk for contrast induced nephropathy include those patients with preexisting kidney impairment (serum creatinine ≥ 1.3 mg/dL or a GFR < 60 mL/min).  Other factors included are hypertension, hemodynamic instability, dehydration, older age (age > 75 years), congestive heart failure and higher doses of contrast media. Regarding preprocedural hydration, the fluids are administered orally or intravenously. However, the recommendation is to not use oral fluids alone in patients at increased risk for contrast-induced nephropathy.

Contrast Extravasation

Extravasated contrast material could potentially lead to compartment syndrome if enough contrast material leaks into surrounding tissue. Typical rates of contrast injections are 4 to 6 cc/s for vascular examinations.

Treatment for contrast extravasation includes elevation of the extremity and cold compresses. A thorough physical assessment should be performed including evaluation of capillary refill and distal pulses. A thorough neurological exam should also be performed.  Plastic surgery should be consulted as necessary, and this consultation is often initiated by the radiologist.

Patients taking Metformin

Patients who take metformin or metformin-containing medications and are scheduled for imaging studies are challenging to manage because they are at risk of developing lactic acidosis. Lactic acidosis has been reported to be fatal in some cases. Given that Metformin is excreted unchanged by the kidney, patients with renal dysfunction will have higher than expected serum levels and are at risk of developing lactic acidosis. In addition, individuals with very poor cardiac function or acute hepatic compromise have increased lactate production or impaired lactate breakdown and also are at risk of developing lactic acidosis. For all such patients, the use of metformin is contraindicated.

The Metformin package insert which was approved by the U.S. Food and Drug Administration states that metformin use should be stopped at the time an iodinated contrast agent is administered and that the patient should wait 48 hours before resuming use of metformin. There is no mandate to measure serum creatinine levels at that time. Instead, the patient should be reevaluated clinically, and a creatinine value should be obtained if there are any other reasons that the patient’s renal function may have been compromised, such as major surgery or cardiogenic shock.

The major point to remember is that metformin is contraindicated in patients with any compromise in renal function. It is surprising how often patients who take metformin and who have elevated serum creatinine levels are referred for a contrast agent study. In these patients, the imaging study should be delayed, and the referring physician should be notified (Bettmann, 2004).

Shellfish allergy and allergy to iodinated contrast agents: Truth or Myth?

Clinical providers including some radiologist have commonly believed that there is a link between an allergic reaction to shellfish and increased risk of allergic reaction to iodinated contrast agents. This connection between an allergy to shellfish and iodinated contrast agents was first reported in the 1970’s. The assumption is based on the fact that both shellfish and iodinated contrast contain significant amounts of iodine. This idea has led some providers to encourage premedication of patients who self-report a shellfish allergy prior to the administration of iodinated contrast agents.  Premedication is usually done with corticosteroids or antihistamines. So, providers have even gone as far as recommending that iodinated contrast media not be administered at all.

Shellfish allergy remains one of the most common food allergies among adults and also remains a common cause of anaphylactic reactions related to food consumption. Shellfish are separated into two groups; the crustaceans also known as arthropods and the molluscs. Examples of arthropods include; crab, lobster, prawn and shrimp while molluscs include; clams, mussels and oysters. Like most other allergic reactions, the treatment for shellfish allergies is antihistamines, corticosteroids and epinephrine if needed.

Allergies to shellfish are mainly due to tropomyosins and iodine has been shown to have no contributory effects to the allergic reactions. Additionally, iodine plays a significant role in the human survival because and used by the thyroid gland for functions essential to human life.

Reactions to iodinated contrast are not true allergic reactions in that they are not mediated by IgE but rather they occur by direct stimulation of mast cells and basophils. The stimulation of these cell types yields a pseudo-allergy like reaction also known as anaphylactoid reactions whereas a true allergic reaction would produce allergy specific immunoglobulin E (IgE) following exposure making the patient sensitized to the allergen. Finally, the anaphylactoid reaction that occurs with iodinated contrast media does not occur due to iodine but rather occurs due to the hyperosmolality of the contrast media compared to blood. Even though a large number of providers continue to specifically inquire about shellfish allergy as a way to screen for allergies to iodinated contrast, there is no evidence to support the practice, and it is recommended that the practice is discontinued (ACR, 2016).

Contrast agent use in breastfeeding women

The half-life of intravenously administered iodinated contrast agents is around 2 hours by which time almost 100% of the agent is cleared from the bloodstream in patients with normal baseline renal function (provided it was last measured in the previous 24-hour period).

Given that iodinated contrast agents have low lipid solubility, less than 1% of the agents administered are excreted into breast milk. Of the amount of contrast agents ingested by breastfeeding babies, less than 1% is absorbed from the infant’s gastrointestinal tract. In effect, the dose presumably absorbed by a breastfeeding infant via their mother’s milk is less than 0.01% of the dose administered intravascular to the mother.

In comparison, this dose is less than 1% of the standard dose which would be prescribed to a similar infant for the performance of an iodinated contrast enhanced imaging study. The standard dose is usually 1.5 to 2 mL/kg for infants.

The risk to the infant are direct toxicity and allergic sensitization or potentially an allergic reaction. It is important to note that these risks remain theoretical and have not been reported in literature. There is also a risk that if the contrast agent is secreted in the mother’s milk, it may alter the taste of the milk.

The American College of Radiology recognizes that an informed decision to temporarily stop breastfeeding is one which is made by the mother. However, their recommendation is it is safe for the mother and the infant to continue breastfeeding during the administration of iodinated contrast agents given that the available data supports this position. If the mother still has concerns after reviewing the available data, she could defer breastfeeding for 24 to 48 hours after the administration of the iodinated contrast agent (ACR, 2016).

Case Scenario

You are a nurse working on a medical surgical floor when you get an order for a CT of the abdomen and pelvis with IV and oral contrast in a patient with suspected diverticulitis. The patient has a shellfish allergy with the documented allergic response being anaphylaxis. In addition, the patient has a documented allergy to “Iodine” with no specific reaction listed. As the nurse on the floor, the patient raises concerns about receiving iodinated contrast given that they have a severe allergy to contrast. How should you address this dilemma?

Discussion:

The first step is to clarify the patient’s allergy list especially when you have certain allergies with undocumented allergic responses. In this case, the patient has an allergy to Iodine with an undocumented response. The first thing to realize is an iodine allergy is incompatible with life because the thyroid gland uses iodine to make thyroid hormone which is necessary for life. The bodies need for iodine is true even for patients with congenital hypothyroidism. So, an allergy to iodine is just like saying you are allergic to calcium which is an essential element for life. Consequently, the allergy to iodine should be deleted from the patient's record. Now the patient may have an allergy to some iodine containing substances, and that should be clarified and documented accordingly. For example, a patient could be allergic to betadine due to sensitization, and this should be documented properly in the record, but an allergy to betadine does not necessarily imply an allergy to iodinated intravenous contrast agents. Most of the time, the allergy is to other substances in the iodine rich materials and not to the iodine itself.

Finally, an allergy to shellfish does not confer a related allergy to iodinated contrast agents. This belief has been erroneously promulgated in medical literature and among the healthcare community, especially among the nursing community. Allergies to shellfish are true IgE mediated allergic reactions due to tropomyosins whereas the anaphylactoid reaction to iodinated contrast agents is secondary to the hyperosmolality of the contrast media compared to blood and are mediated by mast cells and basophils.

Summary

Adverse reactions to contrast agents are an understandable cause for concern for both patients and clinical providers. A thorough understanding of true allergies to contrast agents and how to manage these reactions is necessary for clinicians in today’s practice. With the increasing ubiquitous use of electronic medical records, a history of an allergy to contrast agents either real or perceived could easily get promulgated in the medical record. It is important for all clinicians to fully understand the typical adverse reactions to contrast agents especially nurses who are often responsible for documenting allergies in the medical record. When documenting allergies in the medical record, it is imperative to clarify what the exact allergy is. The patient should be educated about side effects of each contrast agent being administered given that inaccurately documented allergies to contrast agents may limit the ability for providers to get appropriate diagnostic tests in the future. Finally, it is imperative for clinical providers to understand that an allergy to a certain contrast agent does not imply automatic contraindication to that agent. Clinical decisions should be made on each patient’s case, based on the risk-benefit ratio of the ordered test. For example, if a patient needs a lifesaving cardiac catheterization procedure, a mild adverse reaction to intravenous iodinated contrast agents becomes negligible.

References:

ACR. (2016) “ACR Manual on Contrast Media Version 10.2” American College of Radiology. ACR committee on Drugs and Contrast Media. (Visit Source)

Baig, M. (2014). Shellfish allergy and relation to iodinated contrast media: United Kingdom survey. World Journal of Cardiology,6(3), 107. doi:10.4330/wjc.v6.i3.107

Bettmann, M. A. (2004). Frequently Asked Questions: Iodinated Contrast Agents. RadioGraphics,24(Suppl_1). doi:10.1148/rg.24si045519

Broome, D. R., Girguis, M. S., Baron, P. W., Cottrell, A. C., Kjellin, I., & Kirk, G. A. (2007). Gadodiamide-Associated Nephrogenic Systemic Fibrosis: Why Radiologists Should Be Concerned. American Journal of Roentgenology,188(2), 586-592. doi:10.2214/ajr.06.1094

Di Carli, M. F., Solomon, S. D., & Kwong, R. Y. (2015). Noninvasive Cardiac Imaging: Echocardiography, Nuclear Cardiology, and Magnetic Resonance/Computed Tomography Imaging. In D. Kasper, J. Loscalzo, J. Jameson, A. Fauci, S. Hauser, & D. Longo (Authors), Harrison's Principles of Internal Medicine, 19e (19th ed.). New York, NY: McGraw-Hill.

Grobner, T. (2006). Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrology Dialysis Transplantation,21(6), 1745-1745. doi:10.1093/ndt/gfl294

King, S. B., Iii. (2011). Cardiac Catheterization, Cardiac Angiography, and Coronary Blood Flow and Pressure Measurements. In V. Fuster, R. A. Walsh, R. A. Harrington, & M. J. Kern (Authors), Hurst's The Heart (13th ed.). New York, NY: McGraw-Hill.

Marckmann, P., Rossen, K., & Slov, L. (2006). Nephrogenic Systemic Fibrosis: Suspected Causative Role of Gadodiamide Used for Contrast-Enhanced Magnetic Resonance Imaging. Journal of the American Society of Nephrology,17(9), 2359-2362. doi:10.1681/asn.2006060601

Mukundan, S. L., Jacobson, F., Sodickson, A., Ross, J. J., Dressler, D. D., & Scheurer, D. B. (2017). Patient Safety Issues in Radiology. In S. C. McKean (Author), Principles and Practice of Hospital Medicine, (2nd ed.). New York, NY: McGraw-Hill.

Prince, M. R., Zhang, H. L., Roditi, G. H., Leiner, T., & Kucharczyk, W. (2009). Risk factors for NSF: A literature review. Journal of Magnetic Resonance Imaging,30(6), 1298-1308. doi:10.1002/jmri.21973

Prince, M. R., Zhang, H., Morris, M., Macgregor, J. L., Grossman, M. E., Silberzweig, J., . . . Valeri, A. M. (2008). Incidence of Nephrogenic Systemic Fibrosis at Two Large Medical Centers. Radiology,248(3), 807-816. doi:10.1148/radiol.2483071863

Sadowski, E. A., Bennett, L. K., Chan, M. R., Wentland, A. L., Garrett, A. L., Garrett, R. W., & Djamali, A. (2007). Nephrogenic Systemic Fibrosis: Risk Factors and Incidence Estimation. Radiology,243(1), 148-157. doi:10.1148/radiol.2431062144

Weigle, J. P., & Broome, D. R. (2008). Nephrogenic systemic fibrosis: Chronic imaging findings and review of the medical literature. Skeletal Radiology,37(5), 457-464. doi:10.1007/s00256-008-0464-1

Zaer, N. F., Amini, B., & Elsayes, K. M. (2015). Overview of Diagnostic Modalities and Contrast Agents. In K. M. Elsayes & S. A. Oldham (Authors), Introduction to Diagnostic Radiology. New York, NY: McGraw-Hill.


This course is applicable for the following professions:

Advanced Registered Nurse Practitioner (ARNP), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Registered Nurse (RN)

Topics:

Advance Practice Nurse Pharmacology Credit, CPD: Practice Effectively, Medical Surgical


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