Complications of Contrast Media

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Chapter 2

Complications of Contrast Media

Gauravi K. Sabharwal

Allergic-Like Reactions

Introduction

Contrast media are an essential aid in diagnostic medical imaging. A multitude of radiologic examinations are performed daily using these agents. They are used primarily to enhance the visibility of blood vessels, organs, and pathology in the body. Contrast media are considered pharmacologic agents, and, like any other medication, they are not without adverse effects.

Incidence

Scant data are available regarding the incidence of contrast reactions in children for at least three reasons: (1) few clinical trials with children as subjects have been performed to obtain federal approval of an agent,¹ (2) assessing symptoms, particularly mild ones in very young children, is difficult, and (3) differentiating true contrast reactions from symptoms is difficult because of sedation, synchronous medications, anxiety, and other preexisting diseases.²

In the pediatric population, use of nonionic contrast media is discriminative and exclusive when administered intravenously.³ Administration of nonionic contrast is associated with a much lower incidence of contrast media–related adverse effects.² Dillman et al⁴ reported a 0.18% incidence of acute allergic-like reactions to intravenous (IV) administration of nonionic iodinated contrast material in children. This finding is very similar to an incidence of 0.23% in the adult population reported by Cochran et al.⁵ Most of the contrast reactions are mild in both children⁴ and adults.^2,5–7 Of all the reported allergic reactions in children, 15% (<0.03% overall) were severe in degree.⁴ Fatal reactions to contrast media have occurred, but they are very rare. A large Japanese study did not blame any fatalities on contrast media in more than 170,000 injections.⁶ The very low or negligible reported fatalities likely suggest aggressive preventive measures and advancement in management of these reactions.² Delayed reactions have been described in adults and may occur between 1 hour and 2 days after contrast administration. These reactions are predominantly cutaneous and usually resolve within 7 days.^8–10

Risk Factors

As with adults, children need to be appropriately screened before contrast media are administered. Screening includes a complete and specific history from the accompanying parents/responsible adults. Attempts should be made to identify any variables that may preclude the use of the contrast media or potentially increase the eventuality of an adverse reaction to this agent. The following list outlines a few of these factors.

1. Known prior reaction to contrast media, which markedly increases the risk of subsequent reactions.6,11–13

2. Known allergies to food products or medications; minor allergies do not pose a significant risk, but a prior anaphylactic reaction to any substance should heighten awareness of the possibility of a similar reaction to contrast media administration.

3. A history of asthma may increase the incidence of contrast reaction.6,13

4. Known renal disease; renal function in such patients can worsen after administration of contrast media.

5. Known heart disease, sickle cell disease, or diabetes mellitus; patients with these diseases may be at increased risk for contrast reactions.

Other disease entities, such as pheochromocytoma, dehydration, heart failure, severe hyperthyroidism, and β-blocker therapy, that are known risk factors in adults have not been studied in the pediatric population (Box 2-1).

Box 2-1 Risk Factors for Allergic-Like Contrast Reactions

Prior reaction to contrast media

Prior anaphylactic reaction

Moderate to severe allergies to food products or medications

History of asthma

Preexisting renal or heart disease

Diabetes mellitus or sickle cell disease

Concomitant use of certain medications

Pathogenesis

The exact pathogenesis of untoward events after the administration of contrast media remains obscure and poorly understood. Most of the symptoms resemble an allergic or anaphylactoid reaction to a medication or allergen. However, definitive evidence is lacking that these reactions are truly allergic reactions because antibodies and the typical allergic cascade to these agents have not been identified.¹³

Classification of Allergic-Like Contrast Reactions

Based on severity, contrast reactions can be classified as mild, moderate, or severe. Flushing and a sensation of warmth are considered physiologic responses (Box 2-2).

Mild reactions are usually of short duration and resolve without the need for any treatment. However, patients should be carefully observed until the symptoms resolve because the symptoms could progress to more severe reactions.

Moderate reactions require some form of treatment. More importantly, close observation is essential until the symptoms resolve. Vital signs should be monitored and IV access should be secured.

Severe reactions, which are rare, can be life threatening. They could present a worsening of mild or moderate reactions. Prompt and aggressive treatment may be required. The assistance of a rapid response or code team often may be necessary.

Management

In the event of any adverse reaction to contrast media, the IV contrast injection should be discontinued. All reactions and management of the reactions should be documented in the patient care notes, and notation of a contrast allergy should become part of the patient’s permanent medical record. The following protocols closely follow the American College of Radiology (ACR) guidelines for management of acute reactions in children.² The specific agents used in the management of an adverse reaction are determined by individual institutional pharmacy formulary and policy. Some institutions require the radiology personnel to call for assistance (e.g., a rapid response team) if they administer IV epinephrine for the management of these adverse reactions (given the rare incidence of these events and hence the lack of uniformity in preparedness for these reactions).^14,15 To be prepared for such reactions, weight-based dosages of the medications used for management should be posted in clearly visible areas where contrast media are administered to children. Regular review of treatment protocols and practice of contrast reaction scenarios should be performed by radiologists and staff. If at any time a patient does not respond to treatment or the situation seems troublesome, it is appropriate to seek additional medical support immediately. This support may be sought from another radiologist in the department or through activation of an institutional rapid response or code team.

Box 2-3

Management of Acute Reactions in Children

Urticaria

• No treatment is needed in most cases.

• For moderate itching, consider an H1-receptor blocker such as diphenhydramine (Benadryl), PO/IM or via a slow IV push, 1 to 2 mg/kg, up to 50 mg.

• If severe itching is present or the urticaria is widely disseminated, consider an α-agonist such as epinephrine (1 : 10,000), 0.1 mL/kg via a slow IV push over 2 to 5 minutes, up to 3 mL.

Facial Edema

• Secure the airway and administer O₂, 6 to 10 L/min (via mask, face tent, or blow-by stream). Monitor electrocardiogram, O₂ saturation (pulse oximeter), and blood pressure.

• Administer an α-agonist such as epinephrine (1 : 10,000), 0.1 mL/kg via a slow IV push over 2 to 5 minutes, up to 3 mL/dose. Repeat in 5 to 30 minutes as needed.

• Consider administering an H1-receptor blocker such as diphenhydramine (Benadryl) IM or via a slow IV push, 1 to 2 mg/kg, up to 50 mg.

• Note: If facial edema is mild and no reaction progression occurs, observation alone may be appropriate. If the patient is not responsive to therapy, call for assistance.

Bronchospasm

• Secure the airway and administer O₂, 6 to 10 L/min (via mask, face tent, or blow-by stream). Monitor electrocardiogram, O₂ saturation (pulse oximeter), and blood pressure.

• Administer an inhaled β-agonist (e.g., a bronchiolar dilator such as albuterol [Proventil or Ventolin]), 2 to 3 puffs from a metered dose inhaler. Repeat as necessary.

• If bronchospasm progresses, administer epinephrine (1 : 10,000), 0.1 mL/kg via a slow IV push over 2 to 5 minutes, maximum 3 mL/dose. Repeat in 5 to 30 minutes as needed. If the patient is not responsive to therapy, call for assistance for severe bronchospasm or if O₂ saturation <88% persists.

Laryngeal Edema

• Secure the airway and administer O₂, 6 to 10 L/min (via mask, face tent, or blow-by stream). Monitor electrocardiogram, O₂ saturation (pulse oximeter), and blood pressure.

• Administer epinephrine (1 : 10,000), 0 .1 mL/kg via a slow IV push over 2 to 5 minutes, maximum 3 mL/dose. Repeat in 5 to 30 minutes as needed.

Pulmonary Edema

• Secure the airway and administer O₂, 6 to 10 L/min (via mask, face tent, or blow-by stream). Monitor electrocardiogram, O₂ saturation (pulse oximeter), and blood pressure.

• Administer a diuretic: IV furosemide (Lasix), 1 to 2 mg/kg.

Hypotension with Tachycardia (Anaphylactic Shock)

• Secure the airway and administer O₂, 6 to 10 L/min (via mask). Monitor electrocardiogram, O₂ saturation (pulse oximeter), and blood pressure.

• Elevate the legs 60° or more (preferred) or use the Trendelenburg position.

• Keep the patient warm.

• Administer a rapid infusion of IV or IO normal saline solution or Ringer’s lactate.

• If severe, administer an α-agonist such as epinephrine (1 : 10,000), 0.1 mL/kg via a slow IV push over 2 to 5 minutes, up to 3 mL/ dose. Repeat in 5 to 30 minutes as needed. If the patient is not responsive to therapy, call for assistance (e.g., cardiopulmonary arrest response team or 911).

Hypotension with Bradycardia (Vagal Reaction)

• Secure the airway and give O₂, 6 to 10 L/min (via mask). Monitor electrocardiogram, O₂ saturation (pulse oximeter), and blood pressure.

• Elevate the legs 60° or more (preferred) or use the Trendelenburg position.

• Keep the patient warm.

• Administer a rapid infusion of IV or IO normal saline solution or Ringer’s lactate. Caution should be used to avoid hypervolemia in children with myocardial dysfunction.

• Administer atropine IV, 0.02 mg/kg if the patient does not respond quickly to steps 2, 3, and 4. Use a minimum initial dose of 0.1 mg. The maximum initial dose is 0.5 mg (for an infant/child) or 1.0 mg (for an adolescent). May repeat every 3 to 5 minutes up to maximum dose up to 1.0 mg (for an infant/child) or 2.0 mg (for an adolescent). If the patient is not responsive to therapy, call for assistance.

IO, Intraosseous; IM, intramuscular; IV, intravenous; PO, by mouth.

From American College of Radiology Committee on Drugs and Contrast Media. ACR manual on contrast media, 7th ed. 2010. Available at http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/Contrast%20Manual/FullManual.pdf. Accessed June 26, 2012.

Delayed Reactions

Delayed reactions appear to occur more frequently than acute/immediate reactions to administration of contrast media. The incidence ranges from 2% to 12%.8,9 No definite data are available on the incidence and symptoms of delayed reactions in children. In adults, rash, itching and other cutaneous manifestations predominate.⁹ Other symptoms include fevers, chills, nausea, vomiting, headaches, abdominal pain, drowsiness, and dizziness.⁹ These symptoms can manifest any time from 1 hour to 2 days after administration of the contrast agent and usually resolve spontaneously by 7 days.^8–10

Prevention

Before any study requiring administration of IV contrast media is begun, it is imperative to identify patients who would be at high risk for adverse reactions. If risk factors are identified, the need for the examination should be reassessed with the ordering clinician. Other modalities that may offer the same level of diagnosis but do not require administration of contrast agents should be considered. The possibility of performing the same test without the use of contrast media also should be entertained.

Ultimately, if the examination is considered absolutely necessary, the patient with known risk factors for adverse reactions should be premedicated with a combination of an antihistamine and corticosteroids. The regimen suggested by the ACR ² is described in Table 2-1.

Table 2-1

Pediatric Premedication Regimen for Prevention of Contrast Reaction

Medication	Dosage	Timing
Prednisone	0.5-0.7 mg/kg PO (up to 50 mg)	13, 7, and 1 hour before contrast injection
Diphenhydramine	1.25 mg/kg PO (up to 50 mg)	1 hour before contrast injection

PO, by mouth.

Extravasation

Extravasation is a well-recognized complication of contrast-enhanced imaging that occurs in approximately 0.7% of all injections.16–19

Risk Factors

Extravasation is more prone to occur in patients who are unable to verbalize their symptoms, such as infants, younger children, and severely ill and unconscious patients.20,21 Increased rates also are noted in patients receiving chemotherapy, likely because of increased friability of the vein wall.^21,22,23

Other risk factors include the site of injection, IV access type, and the method of injection.²¹ Wang et al¹⁶ noted that although the antecubital fossa was the single most common extravasation site, most of these events occurred in patients with venous access elsewhere. Increased incidents have been noted with injections at the dorsum of the hand.²⁴ Other risk factors also include venous thrombosis, extremity edema, multiple venous access attempts, and use of a tourniquet.^2,20,21 Extravasations are more frequent where preexisting catheters are used as access sites for administration of the contrast media.²² At least two studies did not note any significant difference in the incidence of extravasation with the use of power injectors (Box 2-4).^24,25

Presentation

The immediate symptoms of extravasation can be quite variable. Some patients present with a burning sensation, whereas others remain asymptomatic. Close attention should be paid to young children and unconscious patients because they may not be able to express these sensations. On physical examination, the extravasation site may be red, swollen, and tender.²

Most incidents are self-limiting and resolve spontaneously within 1 to 2 days. These incidents usually are restricted to the skin and subcutaneous tissue.² The injuries can range from transient tightness of the skin to tissue ulceration and necrosis to acute compartment syndromes. Severe reactions have been observed with both small and large volumes of extravasated contrast. However, the majority of severe reactions have been observed with larger volumes (Box 2-5).²⁶

Box 2-5 Signs and Symptoms of Contrast Extravasation

Pain, erythema, burning and/or tingling, tightness, swelling at the affected extremity

Blisters, skin ulceration, soft tissue necrosis

Compartment syndrome

Altered tissue perfusion

Paresthesia

Diminished arterial pulses

Management

A definite treatment approach has not been accepted because of a lack of consensus on the appropriate management of extravasation.20,27,28 Minor symptoms can be treated with elevation of the affected extremity above the level of the heart to help reduce edema by promoting resorption of the fluid.^2,21 Sufficient data are lacking to support either warm or cold compresses over the affected limb.² Hyaluronidase injected subcutaneously may help speed resorption, but insufficient evidence exists to suggest routine use. Regardless, close monitoring of the patient is warranted. These events should be documented in the patient’s medical records and appropriate directions should be provided to seek medical attention in the event of worsening symptoms.

Severe extravasation injuries require a surgical consultation. Such injuries may present as worsening of pain or swelling, skin blistering, decreased capillary refill, diminished pulses, and a change in sensation of the affected extremity.2,20 Wang et al¹⁶ noted in their observations that compartment syndrome can develop even with less than 100 mL of extravasated fluid. Thus it is prudent to conclude that signs and symptoms, rather than the volume extravasated, should be used as a scale for seeking surgical consultation (Box 2-6).

Box 2-6 Management of Contrast Extravasation

Elevation of extremity

Cold/warm compresses

Frequent monitoring of capillary refill, arterial pulses

Frequent questioning for progression of symptoms

Surgical consult

Contrast-Induced Nephropathy

Limited data are available on the nephrotoxic effects of iodinated contrast media in children. The ACR recommends following the principles used for adults in the prevention and management of contrast-induced nephropathy (CIN).² Risk factors for the development of CIN include preexisting renal insufficiency, diabetes mellitus, and multiple contrast media administrations during the same day.

CIN has been described as either an absolute increase in serum creatinine by at least 0.5 mg/dL within 48 hours of contrast injection ²⁹ or an increase of more than 25% within 72 hours of contrast administration.³⁰ However, serum creatinine cannot be reliably used as a measure of renal function in this setting in the pediatric population.² The estimated glomerular filtration rate (GFR) is used widely for this purpose. The National Kidney Disease Education Program has provided information regarding the measurement of GFR at its website (http://www.nkdep.nih.gov/lab-evaluation/gfr-calculators.shtml) and advocates use of the bedside isotope dilution mass spectrometry–traceable Schwartz GFR calculator for children equation³¹:

A GFR of less than 30 mL/min is associated with an increased risk of CIN. Cystatin C, a protein that is produced by all nucleated cells and is exclusively eliminated by glomerular filtration, has been suggested as a better indicator of GFR than serum creatinine.

No significant studies have been conducted to understand the nephrotoxic effects, risk factors, or prevention of CIN in children. Hence when CIN is a concern for a pediatric patient, the clinician ordering the test and the radiologist must carefully consider the need for the study and the potential use of other modalities or unenhanced imaging.

Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis is a disease characterized primarily by skin fibrosis, but it may involve multiple organs. Its association with gadolinium-based contrast agents has been realized and was first documented in 2006.³² Nine pediatric cases have been reported as of 2008, with the patients ranging in age from 8 to 19 years.³³ Not enough data exist in the pediatric population to provide guidelines for the prevention of nephrogenic systemic fibrosis in children. The ACR² recommends following adult guidelines for identifying patients at risk and the use of gadolinium-based contrast media. The suggested risk factors are acute renal failure, decreased renal function with GFR less than 30 mL/min, high doses of administered gadolinium, and postsurgical status.^32,34,35 Only a limited number of gadolinium-based contrast agents have been studied and approved by the Food and Drug Administration for use in children younger than 2 years.³³ Gadolinium agents should be used with caution in infants and preterm babies because their renal function is immature.³³