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Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment
Journal of Radiology Nursing xxx (2019) 1e7
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Article Review
Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment Nicolette L. Dumas, MD a,*, Kendall P. Crookston, MD, PhD b a b
Department of Radiology, University of New Mexico, Albuquerque, New Mexico, USA Department of Pathology, Department of Medicine, University of New Mexico, Albuquerque, New Mexico, USA
a b s t r a c t Keywords: Acute transfusion reaction Iodine contrast reaction Treatment of transfusion reaction Treatment of contrast reaction
Acutely ill patients receive many treatments, some of which can cause serious reactions. It is not unusual for a critically ill patient to receive blood products and low osmolar nonionic iodine-based contrast material in close proximity to one another. If the patient appears to develop a reaction during the administration of either iodine-based contrast or transfusion, it may be difficult to determine whether the patient is experiencing a transfusion reaction or a contrast reaction. This article explores different types of acute reactions resulting from administration of blood products or iodine-based contrast and how to differentiate between these reactions. Only iodine-based contrast reactions and acute transfusion reactions are discussed, as these are by far the most common and most serious types of reactions that will occur. Bedside management of both types of reactions is also explored. In conclusion, timely recognition of acute transfusion and iodine-based reactions, along with an understanding of the differences and similarities between these reactions, enables the clinical team to appropriately evaluate and treat the patient for these potentially life-threatening events. Published by Elsevier Inc. on behalf of the Association for Radiologic & Imaging Nursing. All rights reserved.
Introduction to Blood Transfusion Blood product transfusions are lifesaving and are performed millions of time each year, usually without incident. Common types of transfusions include packed red blood cells, plasma, platelets, and cryoprecipitate. Blood product transfusion may be considered a liquid transplant as it involves the introduction of active biologic products from a living donor to a patient. The patient may have a variety of complex reactions to these living cells and proteins. This article will focus on acute transfusion reactions, as those are more likely to be encountered, especially in conjunction with iodinebased contrast administration. Transfusion protocols are optimized to detect the potentially lethal acute hemolytic transfusion reaction, but the bedside nurse is more likely to see the more common transfusion reactions. Acute transfusion reactions include mild allergic reaction, febrile nonhemolytic reaction, transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), bacterial contamination, anaphylactic reactions, and acute hemolytic transfusion reactions. Mild allergic and febrile nonhemolytic transfusion * Corresponding author: Nicolette L. Dumas, Department of Radiology, MSC10 5530, 1 University of New Mexico, Albuquerque, NM 87131. E-mail address: [email protected] (N.L. Dumas).
reactions comprise most acute transfusion reactions that will be encountered at the bedside. Figure 1 demonstrates the relative frequencies of different transfusion reactions.
Pathophysiology of Common Acute Transfusion Reactions Acute transfusion reactions are generally immune-mediated reactions. The only acute transfusion reaction discussed in this article that is not immune mediated is TACO. A brief overview is given of common etiologies. Discussions that are more exhaustive are available elsewhere (Crookston, Koenig, & Reyes, 2015; Suddock & Crookston, 2018). Mild allergic reactions occur secondary to hypersensitivity to protein or other substance found in the blood product. Febrile nonhemolytic reactions are diagnosed if there is an unexplained 1 C increase in temperature while the blood product is being infused. This can occur because of cytokine buildup in the transfused blood or by recipient antibodies activating donor white blood cells, resulting in cytokine release. TACO results when administration of blood products can result in acute pulmonary edema because of excessive fluid transfusion. The elderly, neonates, and patients with heart failure,
https://doi.org/10.1016/j.jradnu.2019.11.003 1546-0843/$36.00/Published by Elsevier Inc. on behalf of the Association for Radiologic & Imaging Nursing. All rights reserved.
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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renal disease, and anemia are most susceptible to dyspnea secondary to volume overload. TRALI is defined as acute lung injury that occurs within 6 hr of blood product transfusion. This is a diagnosis of exclusion, as the lung injury cannot be attributed to other causes of lung injury, such as pneumonia. This is more often seen in blood products high in plasma content. The transfusion product contains antibodies that then activate the neutrophils causing the signs and symptoms of TRALI. The patient usually has a clinical condition where the pulmonary epithelium has become activated with increased numbers of neutrophils present (Vlaar et al., 2019). The chest radiograph and CAT scan will show pulmonary infiltrates similar in appearance to acute respiratory distress syndrome. Bacterial contamination is caused by administration of blood products contaminated with bacteria. This is most commonly seen in platelet transfusions. Anaphylactic reactions are severe allergic reactions caused by a patient antibody to a donor protein that activates cells such as mast cells and basophils, which then degranulate and cause the severe symptoms encountered (Reber, Hernandez, & Galli, 2017). Acute hemolytic reactions are caused by patient antibody reacting to donor red blood cell proteins, resulting in hemolysis of the donor cells. This usually is caused by ABO incompatibility.
Onset of Acute Transfusion Reactions Acute transfusion reactions typically occur during the first 24 hr after transfusion. Most occur during the transfusion itself. The typical time course for presentation of acute transfusion reactions is summarized in Figure 2. Common Symptoms of Transfusion Reaction Common symptoms that occur during transfusion reactions include (but are not limited to) fever, hypotension, rigors, urticaria, hypoxia, and dyspnea. The types of common acute transfusion reactions and their associated symptoms are summarized in Table 1. Fever, hypotension, and dyspnea are discussed further as they can be used to help distinguish between common acute transfusion reactions, which are summarized in Figure 3. Fever may indicate a transfusion reaction. It is normal to have slight temperature variations (± 0.5 C) while administering blood (Crookston et al., 2015). An increase in temperature of 1 C
Figure 1. Relative frequency of complications associated with blood transfusion. The approximate incidence is given per unit transfused. Note that some reactions are more likely to be associated with certain components (e.g., bacterial contamination / platelets; acute hemolytic reactions / RBC). The graph is not drawn to scale. Abbreviations: RBC ¼ red blood cell; TACO ¼ transfusion-associated circulatory overload; TRALI ¼ transfusion-related acute lung injury. Graphic design by Kimberly Crookston Hill. Reprinted with permission (Crookston et al., 2015).
Figure 2. Time course for the typical presentation of transfusion reactions. The bracket emphasizes those reactions that begin during transfusion or later on day 1. Refer to Table 1 for specific signs and symptoms associated with each reaction type. Abbreviations: TACO ¼ transfusion-associated circulatory overload; TRALI ¼ transfusionrelated acute lung injury; TA-GVHD = transfusion associated graft versus host disease. Graphic design by Kimberly Crookston Hill. Reprinted with permission (Crookston et al., 2015).
or more could indicate a simple febrile reaction or the more serious hemolytic or septic reactions. Hypotension may indicate a more serious, potentially lethal reaction, which includes acute hemolysis, anaphylaxis, bacterial contamination, and acute lung injury. Dyspnea during a transfusion may be the result of the patient's underlying condition, such as congestive heart failure. TACO is the most common reason for a transfusion recipient to become dyspneic although TRALI is also within the differential. It is very important to distinguish between TACO and TRALI, as TACO is treated with diuretics and diuretics can worsen TRALI (Crookston et al. 2015). Hives and/or itching are signs seen with the most common transfusion reaction, mild acute transfusion reaction. These symptoms are not restricted to mild acute transfusion reactions and can rapidly progress into anaphylactic reactions. It is difficult to distinguish at the time of onset of hives/itching whether this reaction will proceed to an anaphylactic reaction so the patient needs to be monitored closely.
Treatment of a Suspected Transfusion Reaction The single most important thing to do when a transfusion reaction is suspected is to stop the transfusion immediately and keep the line open. There are usually forms provided by the institution to document the transfusion reaction, with instructions about which post-transfusion blood specimens to draw for the blood bank investigation. Laboratory testing is helpful with diagnosing what caused the reaction. The blood bag, infusion set, and anything else attached to the set should be sent to the laboratory for further evaluation. Determining why the reaction occurred is very important, as it may affect treatment and whether the patient can receive blood products in the future. Furthermore, if the products were contaminated in any way, other blood components from that same donor need to be removed from the shelf. In general, once a transfusion is stopped, it should not be restarted. Treatment of the reaction depends on the type of reaction that is occurring. Diphenhydramine and acetaminophen are used for mild allergic and febrile nonhemolytic reactions. In more serious and
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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Table 1 Signs and symptoms typically seen during acute transfusion reactions Acute complications of transfusion Complication
Signs and symptoms
Mild allergic reaction Febrile nonhemolytic reaction Volume overload/transfusion-associated circulatory overload (TACO) Acute lung injury/transfusion-related acute lung injury (TRALI)
Urticaria and pruritis Fever and chills Dyspnea, orthopnea, tachycardia, congestive heart failure, headache Dyspnea, hypoxia, hypotension, can look similar to acute respiratory distress syndrome (ARDS) on imaging Findings of sepsis including rigors, fever, hypotension. Most commonly seen in platelet transfusions Respiratory distress, shock, hypotension Fever, chills, nausea, hypotension, back or chest pain, hematuria, shock
Bacterial contamination Anaphylaxis Acute hemolytic reaction
complicated cases, consulting an expert should be considered. In all cases of hemolytic transfusion reaction, baseline laboratory values should be obtained, with administration of intravenous (IV) fluids to protect the kidneys, as the increased free hemoglobin in the blood from red blood cell lysis may cause kidney damage. TACO may be treated with diuretics. TRALI is treated with oxygen and supportive care, which may include intubation. Bacterial contamination may require blood pressure support and antibiotics. Anaphylaxis is treated per hospital protocol, usually with epinephrine and diphenhydramine. It is controversial whether premedication with diphenhydramine and acetaminophen should be given to prevent mild transfusion reactions, as several controlled trials demonstrated that premedication does not prevent such reactions (Crookston et al. 2015). Introduction to radiological contrast media There are two basic types of iodine-based contrast: high osmolar and low osmolar. High osmolar contrast is rarely used anymore as it
has a significantly higher incidence of complications including a 6fold increase in contrast reactions. Higher incidence of renal toxicity is also associated with high osmolarity contrast media that has an osmolarity of 1,570 mosm/kg. Low osmolar nonionic iodine-based contrast is almost ubiquitously used today as it is associated with fewer reactions and less renal toxicity with an osmolarity of 290e672 mosm/kg and will be the subject of this discussion (Salijoughian, 2012). Iodine-based contrast is often used for computed tomography scans (CT scans) and during procedures performed in interventional radiology, cardiology, and gastroenterology. The volume administered during a CT scan varies from institution to institution, as there are weight-based and fixed contrast media dosing protocols. The volume of iodinated contrast used during interventional radiology, gastroenterology, and cardiology procedures varies widely and depends on the type and complexity of the procedure being performed. Reactions to IV iodinated contrast, whether it is used for a CT scan or for other procedures, have an incidence of 0.2e0.7%. Severe contrast reactions (e.g., anaphylaxis) occur in 0.1% of people receiving IV iodine contrast, with death occurring in approximately 1:170,000 receiving contrast injections (Beckett, Moriarity, and Langer, 2015). Acute reactions typically occur within 20e60 minutes of iodinebased administration of contrast media. Delayed reactions are those that occur outside of the 60-minute time interval. Risk factors for having a reaction to iodinated contrast media include previous reaction to iodinated contrast, other severe allergies, history of asthma, history of atopy (3- to 6-fold increase), history of cardiac disease, and a history of renal disease. Prior reaction to iodinated contrast media does not guarantee a future reaction but does increase the likelihood of a future reaction by 5- to 6-fold (Beckett, et al., 2015). Types of iodine-based contrast media reactions There are two basic types of reactions that occur with iodinebased contrast media: chemotoxic and allergic. Allergic reactions can further be broken down into true allergic reactions and allergiclike or anaphylactoid reactions (Bohm, Morelli, Nairz, Silva Hasembank Keller, & Heverhagen, 2017).
Figure 3. Transfusion reaction recognition at the bedside. Signs and symptoms help the clinical team differentiate a normal patient response to transfusion from a potential transfusion reaction. *The “normal” vital sign changes during transfusion are approximated for use as a “rule of thumb” to help in recognition of a possible transfusion reaction. When changes fall outside these parameters, special vigilance is needed to monitor for possible reactions. Abbreviations: TACO ¼ transfusionassociated circulatory overload; TRALI ¼ transfusion-related acute lung injury; T ¼ temperature; RR ¼ respiratory rate in respirations per minute (rpm); HR ¼ heart rate in beats per minute (bpm); BP ¼ either systolic or diastolic blood pressure in millimeters of mercury (mm Hg). Graphic design by Kimberly Crookston Hill. Reprinted with permission (Crookston et al., 2015).
Chemotoxic Reaction This is also known as physiologic type reaction. This type of reaction does not involve the immune system and is the body's response to a chemical in the system. The chemotoxic reaction is believed to be caused by a disruption of homeostasis of the body because of increased viscosity and osmolarity of the contrast as compared with serum. The higher osmolarity can cause fluid shifts,
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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leading to cell dehydration. Chemotoxic reactions are, in general, more often seen after interventional procedures where large amounts of iodine-based contrast media may be used (Beckett et al., 2015). Chemotoxic reactions may be classified as mild, moderate, or severe. These may have a variety of symptoms including feeling of warmth, nausea, vomiting, vasovagal reaction, hypertension, headache, chest pain, and seizure. It is important to note that the feeling of warmth is not a true fever. These are further summarized in Table 2. Allergic Reaction True allergic reactions to iodinated contrast occur when the contrast molecule causes a release of the antibody, IgE. This causes a biochemical cascade that can ultimately lead to the signs and symptoms of anaphylaxis. To determine whether the patient is truly having an allergic reaction to iodine-based contrast media, a skin test can be performed; this is rarely performed, as true allergic reactions to iodinated contrast are rare. A positive skin test indicates that a true allergic reaction to iodinated contrast has occurred (Bohm, et al., 2017). These reactions have the typical signs and symptoms of anaphylaxis, including respiratory distress, shock, and hypotension (Brockow, et al., 2005). Allergic-Like Reactions These reactions are also known as anaphylactoid reactions in some literature. These are considered a pseudoallergy because IgE antibody is not released. Despite the name and the lack of antibody response, these reactions can be very severe, even life-threatening. Because these reactions are not antibody mediated, they can occur without prior exposure to iodinated contrast. It has been hypothesized that as the iodine-based contrast moves through the lungs, mast cells become activated, causing these cells to release a large amount of histamine into the blood. The large amount of histamine causes the symptoms that are commonly seen with anaphylactoid reactions, such as hives, dyspnea, hypertension, and hypotension. Other pathways are hypothesized to also become involved in these reactions, such as kinin and complement systems (Dillman, Trout, & Davenport, 2018). Allergic-like contrast reactions may be classified as mild, moderate, or severe. The symptoms include urticaria, pruritus,
hypertension, hoarseness, throat tightness, wheezing, hypoxia, and facial edema. These findings are further summarized on Table 2. Myths Regarding Iodine-Based Contrast Media Reactions It is important to dispel a couple of common myths involving iodine-based contrast media reactions. Concurrent seafood allergies, specifically shellfish allergies, do not increase iodine-based contrast media reactions. It is safe to give a patient with a seafood or shellfish allergy iodine-based contrast media (assuming they have not had a reaction to iodinated contrast media in the past). Topical iodine allergies also do not cross-react with iodinated contrast media allergies. In summary, as long as the patient has not had a previous iodine-based contrast reaction then it is safe to administer iodine-based contrast media to a patient with a topical iodine allergy or seafood allergy (Bohm, et al., 2017; Salijoughian, 2012).
Drug Contraindications Of note, patients who are taking metformin may require the drug to be held 48 hr after administration of iodinated contrast as this combination can potentially cause severe lactic acidosis (Baerlocher, Asch, & Myers, 2013). In general, patients with no evidence of acute kidney injury before the administration of iodinebased contrast do not require metformin to be withheld after contrast administration (Goergen, Rumbold, Compton, & Harris, 2010). Those patients who are known to have acute or chronic kidney disease before administration of metformin should hold the medication for 48 hr after administration of iodine-based contrast. Reinstitution is often only performed after renal function has been re-evaluated. Refer to the local institutional protocol, as these are general guidelines and may vary. Metformin is typically prescribed for diabetics to help control blood sugar. It has been proposed that metformin causes reduced gluconeogenesis in the liver, which then prevents uptake of lactate by the liver, leading to increased lactic acid within the blood stream. Any other process that can lead to increased lactic acid within the body can then potentially lead to lactic acidosis. Renal impairment can lead to decreased clearance of metformin from the body with the higher levels of metformin leading to further decrease in gluconeogenesis and increased lactic acid in the blood stream. There is potential that IV iodine-based contrast could cause transient decrease in renal function, leading to higher levels of
Table 2 Signs and symptoms typically seen during iodine-based contrast reactions Acute complications of iodine-based contrast reactions Physiologic type reaction
Symptoms
Mild
General: flushing, warmth, sneezing, rhinorrhea Cardiovascular (CV): mild hypertension Gastrointestinal (GI): mild nausea or vomiting Central nervous system (CNS): anxiety, vasovagal reaction requiring no treatment, headache CV: chest pain without EKG changes, hypertensive urgency GI: moderate nausea or vomiting CNS: vasovagal reaction requiring treatment CV: hypertensive crisis, arrhythmia, possible EKG changes CNS: seizures, unresponsive/unconscious
Moderate
Severe Allergic type reaction
Symptoms
Mild
General: urticaria, pruritus, rhinorrhea, sneezing, nasal congestion CV: mild hypertension GI: nausea, mild vomiting. General: generalized erythema, urticaria, pruritis, edema Pulmonary: hoarseness, throat tightness, possible mild hypoxia, wheezing General: Severe facial and laryngeal edema. Pulmonary: hypoxia CV: hypotension
Moderate Severe
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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metformin in the blood, and potentially leading to lethal levels of lactic acid (Goergen et al., 2010). The following medications contain metformin; the generic name is followed by common brand name(s) in parentheses: metformin (Glucophage, Glucophage XR, Fortamet, Riomet, Glumetza); glyburide/metformin (Glucovance); glipizide/metformin (Metaglip); linagliptin/metformin (Jentadueto); pioglitazone/metformin (Prandimet); rosiglitazone/metformin (Avandamet); saxagliptin/metformin (Kombiglyze XR); sitagliptin/metformin (Janumet, Janumet XR). Recognition and treatment of iodine-based contrast reactions It is important to closely monitor vital signs during a suspected iodine-based contrast reaction, whether chemotoxic, allergic, or allergic-like. Unlike during blood transfusions, patients who are receiving iodinated contrast media may or may not be under careful vital sign monitoring. If an iodinated contrast reaction is suspected, particularly if it might be moderate or severe, then vital sign monitoring needs to be promptly initiated.
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diphenhydramine can be administered by mouth or intravenously. A nonsedating antihistamine such as fexofenadine can be considered for patients who may need to drive themselves home. Moderate/Severe Monitor vital signs and preserve IV access. Consider 25e50 mg of diphenhydramine (note that diphenhydramine may cause hypotension). Diffuse Erythema For all forms, preserve IV access, monitor vital signs, and administer oxygen. Normotensive with erythema Monitor the patient's vital signs. No other treatment is normally needed Hypotensive with erythema Administer IV saline rapidly. If profound hypotension or unresponsive to fluid resuscitation, then consider administering epinephrine and calling the emergency response team.
Management of Iodine-Based Contrast Reactions
Bronchospasm
Treatment and bedside management of iodinated contrast reactions depend on the presentation and the severity of the reactions that are occurring (Maddox, 2002; Morzycki, Bhatia, & Murphy, 2017). Alerting the clinical team and obtaining vital signs are key first steps. Maintaining the airway and placing the patient on oxygen should be performed for all moderate and severe reactions. Maintaining an IV line or obtaining new access is also critical for moderate and severe reactions. The patient may have stridor and/or expiratory wheezes in which case talking to the patient may make these symptoms more apparent. The patient may describe severe anxiety or crushing chest pain. Differentiating between physiologic, allergic, and allergic-like contrast reactions is not necessarily important at the time of presentation because treatment of the symptoms takes precedence. For any reaction that is deemed to originate from iodinated contrast media, it is critical to update the patient's chart to reflect the reactiondthis is typically listed in the allergy section. It is also important to list the symptoms that occurred during the reaction. This helps guide future decision-making if the patient needs iodinated contrast later, whether contrast may ever be given again, and whether pretreatment with diphenhydramine or steroids might be of benefit. Of note, steroids are not useful in acute treatment of any reaction. Steroids may be used to help prevent shortterm recurrence of an allergic-like reaction (Beckett, et al., 2015). If the patient starts showing symptoms of an acute reaction to iodinated contrast media during a procedure, then the risks and benefits of continuing the procedure must be weighed. Any severe reaction should cause the procedure to be terminated. A clinician may choose to treat mild and potentially moderate reaction symptoms using medications if a critical procedure is underway that cannot be halted.
For all forms, preserve IV access, monitor vital signs, and administer oxygen.
Hives
Hypertensive Crisis
Mild Scattered or transient hives often do not require any treatment. The patient may be observed and no intervention may be needed if the symptoms resolve. If symptoms persist, then 25e50 mg of
Preserve IV access, monitor vital signs, administer oxygen, and administer IV labetalol. The dose can be doubled every 10 minutes. Nitroglycerin may be used in lieu of labetalol. Administer a diuretic such as furosemide. Call emergency response team.
Mild Administer beta agonist inhaler and consider calling the emergency response team if the response to the inhaler in inadequate. Moderate Administer beta agonist inhaler. This can be repeated up to three times. Consider administering epinephrine and calling the emergency response team. Severe Administer epinephrine and IV fluids. If possible, administer beta agonist inhaler. Call the emergency response team. Laryngeal Edema Preserve IV access, monitor vital signs, administer oxygen, call the emergency response team, and administer epinephrine. Hypotension Preserve IV access, monitor vital signs, administer oxygen, elevate legs, and administer fluids (~1,000 mL in adults). If there is hypotension with bradycardia, then this is likely a vasovagal reaction. If the patient remains symptomatic despite the aforementioned measures, consider administering epinephrine. Consider calling the emergency response team.
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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Pulmonary Edema Preserve IV access, monitor vital signs, administer oxygen, elevate head of bed (if possible), administer a diuretic such as furosemide, and call the emergency response team. Seizures Observe and protect the patient. Turn the patient on their side to avoid aspiration, observing cervical spine precautions if necessary and suction airway if needed. Preserve IV access, monitor vital signs, and administer oxygen. Call the emergency response team. If the seizure is unremitting then consider administration of a benzodiazepine such as lorazepam. Differentiating between radiologic contract reactions and transfusion reactions In acutely ill patients, blood products and iodine-based contrast media may sometimes need to be administered simultaneously or in close proximity to one another. For instance, an ICU patient may have just received blood products before being transported to radiology. The blood products and contrast media can both lead to adverse reactions. Rapid recognition of a potential reaction is critical to timely intervention to minimize patient harm. The key is to realize that a reaction is occurring and to take appropriate action. There are several signs and symptoms that can be seen in both iodinated contrast and transfusion reactions, such as hives, chills, dyspnea, and hypotension. Immediately, the acute symptoms need to be managed with a detailed investigation into what is causing the reaction. Acute iodine-based contrast reactions usually occur within 1 hr of administration. If it has been longer than 1 hr since contrast administration and blood products are concurrently being given then the reaction is more likely due to the blood. Blood products are also statistically more likely to cause a reaction, when compared with iodine-based contrast media. When a severe reaction occurs and the cause is in doubt (blood transfusion vs iodine-based contrast reaction), then reaching out to both a radiologist and transfusion specialist is warranted. The medical team can work with both experts to determine the cause of the reaction. Most of the reactions are treated symptomatically but TRALI needs to be identified quickly, as it is treated differently than other acute transfusion or iodinated contrast reactions (Crookston et al., 2015). Common Signs and Symptoms That May Be Seen in Transfusion and Iodine-Based Contrast Reactions Figure 4 illustrates signs and symptoms that may be seen in both transfusion and contrast reactions and the most likely causes. Hives and/or itching can be seen in mild acute transfusion reactions, mild and moderate allergic-like contrast media reactions, and mild physiologic contrast media reactions. These entities are treated the same despite their origin (e.g., consider administration of diphenhydramine). If blood is being administered, then stop the transfusion. The blood product and associated tubing should to be sent to the laboratory for further investigation until it is discovered whether the blood products or an iodinated contrast reaction caused the symptoms. Fever is seen almost exclusively with transfusion reactions. Patients with iodine-based contrast media reactions may experience flushing and warmth but do not typically have increased temperatures.
Figure 4. Recognition and differentiation of transfusion reactions and iodine-based contrast reactions at the bedside. Signs and symptoms help the clinical team to recognize reactions and to formulate a differential diagnosis of possible reactions types. Abbreviations: TACO ¼ transfusion-associated circulatory overload; TRALI ¼ transfusion-related acute lung injury; Rxn ¼ reaction. Graphic design by Kimberly Crookston Hill.
Chills may be seen with either mild or moderate physiologic contrast reactions or mild, moderate, or severe allergic-like contrast reactions as a nonspecific symptom. It can also be seen in acute transfusion reactions, especially with bacterial contamination. Bacterial contamination is most common in platelet transfusion and should be high on the differential with any signs of sepsis. If this occurs then stop the transfusion and the tubing and bag must be sent to the laboratory. Treat the symptoms as necessary. Hypotension is a nonspecific symptom that is seen in both iodinated contrast and acute transfusion reactions. Regardless of origin, hypotension is treated with fluids. Again, when any transfusion reaction is suspected, discontinue the transfusion and send the blood bag and administration set to the laboratory for further testing. Dyspnea is another nonspecific symptom that can be seen with either acute transfusion or iodinated contrast reactions. This is most common with severe allergic-like reactions and can be seen in acute hemolytic, TRALI, or TACO-type transfusion reactions. Determining the cause of dyspnea is crucial as these entities are all treated differently. Inspiratory or expiratory wheezes suggest an anaphylactic reaction and need to be treated appropriately, whether the reaction is caused by a transfusion or iodinated contrast reaction. Occasionally, iodinated contrast can be given in enough volume to give symptoms of volume overload in susceptible populations. This can be treated the same as TACO, with diuretics. Again, it is important to identify TRALI as it is not treated with any of the other previously described medications and can be exacerbated by diuretics (Vlaar et al., 2019). The other symptoms that are common in iodine-based contrast media reactions are not specific to these reactions but can occasionally overlap with symptoms of the patient's acute illness and unusual presentations of transfusion reactions. Conclusion Blood product transfusion and iodine-based contrast may need to be given in close proximity to one another in the acutely ill
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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patient. Both of these entities can cause a variety of reactions, some of which may be life-threatening. Basic knowledge of the most common types of reactions for both entities increases the likelihood of prompt identification of the reaction and initiation of proper treatment. Statistically, acute blood transfusions are more likely to occur than acute iodine-based contrast media reactions. Most reactions to iodinated contrast occur within 1 hour of administration. At bedside, it is critical to identify that a reaction is occurring, as most reactions, whether caused by a transfusion or from iodinated contrast media, are treated symptomatically. If a transfusion is running, then stop the transfusion immediately and keep the line open. The remaining blood that has not yet been administered needs to be saved to be taken to the laboratory for further testing. Vital signs must be monitored closely, with oxygen administration needed for most reactions. Once the patient is stabilized then a detailed investigation into the cause of the reaction needs to be initiated. There is significant overlap in the symptoms of both transfusion and iodine-based contrast media reactions that can make bedside identification difficult. In those cases, there will need to be communication between the medical team, transfusion service, and radiology to identify the cause of the reaction. Useful web links American College of Radiology Manual on Contrast Media: https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Con trast_Media.pdf European Society Of Urogenital Contrast Agent Guidelines: http://www.esur-cm.org/index.php/ Journal of Applied Radiology Review of common and uncommon contrast media reactions: https://appliedradiology.com/articles/ review-of-common-and-uncommon-contrast-media-reactions University of California, San Francisco Department of Radiology and Biomedical ImagingdManagement of Acute Reactions to Contrast Media in Adults: https://radiology.ucsf.edu/patientcare/patient-safety/contrast/iodinated/reactions-adults
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University of California, San Francisco Department of Radiology and Biomedical ImagingdTreatment of Acute Reactions to Contrast Media in Children: https://radiology.ucsf.edu/patientsafety/contrast/iodinated/reactions-children UpToDate ReviewdDiagnosis and treatment of an acute reaction to a radiologic contrast agent: https://www.uptodate.com/ contents/diagnosis-and-treatment-of-an-acute-reaction-to-aradiologic-contrast-agent
References Baerlocher, M.O., Asch, M., & Myers, A. (2013). Five things to know about…metformin and intravenous contrast. CMAJ, 185, E78. Beckett, K.R., Moriarity, A.K., & Langer, J.M. (2015). Safe use of contrast media: what the radiologist needs to know. Radiographics, 35, 1738-1750. Bohm, I., Morelli, J., Nairz, K., Silva Hasembank Keller, P., & Heverhagen, J.T. (2017). Myths and misconceptions concerning contrast media-induced anaphylaxis: a narrative review. Postgraduate Medical Journal, 129, 259-266. Brockow, K., Christiansen, C., Kanny, G., Clement, O., Barbaud, A., Bircher, A., et al. (2005). Management of hypersensitivity reactions to iodinated contrast media. Allergy, 60, 150-158. Crookston, K.P., Koenig, S.C., & Reyes, M.D. (2015). Transfusion reaction identification and management at the bedside. Journal of Infusion Nursing, 38, 104-113. Dillman, J.R., Trout, A.T., & Davenport, M.S. (2018). Allergic-like contrast media reaction management in children. Pediatric Radiology, 48, 1688-1694. Goergen, S.K., Rumbold, G., Compton, G., & Harris, C. (2010). Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology, 254, 261-269. Maddox, T.G. (2002). Adverse reactions to contrast material: recognition, prevention, and treatment. American Family Physician, 66, 1229-1234. Morzycki, A., Bhatia, A., & Murphy, K.J. (2017). Adverse reactions to contrast material: a Canadian update. Canadian Association of Radiologists Journal, 68, 187-193. Reber, L.L., Hernandez, J.D., & Galli, S.J. (2017). The pathophysiology of anaphylaxis. The Journal of Allergy and Clinical Immunology, 140, 335-348. Salijoughian, M. (2012) Intravenous radiocontract media: a review of allergic reactions. U.S. Pharmacist, 37, HS-14-HS-16. Retrieved from: https://www. uspharmacist.com/article/intravenous-radiocontrast-media-a-review-of-allergicreactions. Suddock, J.T., & Crookston, K.P. (2018). Transfusion Reactions. Treasure Island, FL: StatPearls. Vlaar, A.P.J., Toy, P., Fung, M., Looney, M.R., Juffermans, N.P., Bux, J., Bolton-Maggs, P., Peters, A.L., Silliman, C.C., Kor, D.J., & Kleinman, S. (2019). A consensus redefinition of transfusion-related acute lung injury. Transfusion, 59, 2465-2476.
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Contents lists available at ScienceDirect
Journal of Radiology Nursing journal homepage: www.sciencedirect.com/journal/ journal-of-radiology-nursing
Article Review
Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment Nicolette L. Dumas, MD a,*, Kendall P. Crookston, MD, PhD b a b
Department of Radiology, University of New Mexico, Albuquerque, New Mexico, USA Department of Pathology, Department of Medicine, University of New Mexico, Albuquerque, New Mexico, USA
a b s t r a c t Keywords: Acute transfusion reaction Iodine contrast reaction Treatment of transfusion reaction Treatment of contrast reaction
Acutely ill patients receive many treatments, some of which can cause serious reactions. It is not unusual for a critically ill patient to receive blood products and low osmolar nonionic iodine-based contrast material in close proximity to one another. If the patient appears to develop a reaction during the administration of either iodine-based contrast or transfusion, it may be difficult to determine whether the patient is experiencing a transfusion reaction or a contrast reaction. This article explores different types of acute reactions resulting from administration of blood products or iodine-based contrast and how to differentiate between these reactions. Only iodine-based contrast reactions and acute transfusion reactions are discussed, as these are by far the most common and most serious types of reactions that will occur. Bedside management of both types of reactions is also explored. In conclusion, timely recognition of acute transfusion and iodine-based reactions, along with an understanding of the differences and similarities between these reactions, enables the clinical team to appropriately evaluate and treat the patient for these potentially life-threatening events. Published by Elsevier Inc. on behalf of the Association for Radiologic & Imaging Nursing. All rights reserved.
Introduction to Blood Transfusion Blood product transfusions are lifesaving and are performed millions of time each year, usually without incident. Common types of transfusions include packed red blood cells, plasma, platelets, and cryoprecipitate. Blood product transfusion may be considered a liquid transplant as it involves the introduction of active biologic products from a living donor to a patient. The patient may have a variety of complex reactions to these living cells and proteins. This article will focus on acute transfusion reactions, as those are more likely to be encountered, especially in conjunction with iodinebased contrast administration. Transfusion protocols are optimized to detect the potentially lethal acute hemolytic transfusion reaction, but the bedside nurse is more likely to see the more common transfusion reactions. Acute transfusion reactions include mild allergic reaction, febrile nonhemolytic reaction, transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), bacterial contamination, anaphylactic reactions, and acute hemolytic transfusion reactions. Mild allergic and febrile nonhemolytic transfusion * Corresponding author: Nicolette L. Dumas, Department of Radiology, MSC10 5530, 1 University of New Mexico, Albuquerque, NM 87131. E-mail address: [email protected] (N.L. Dumas).
reactions comprise most acute transfusion reactions that will be encountered at the bedside. Figure 1 demonstrates the relative frequencies of different transfusion reactions.
Pathophysiology of Common Acute Transfusion Reactions Acute transfusion reactions are generally immune-mediated reactions. The only acute transfusion reaction discussed in this article that is not immune mediated is TACO. A brief overview is given of common etiologies. Discussions that are more exhaustive are available elsewhere (Crookston, Koenig, & Reyes, 2015; Suddock & Crookston, 2018). Mild allergic reactions occur secondary to hypersensitivity to protein or other substance found in the blood product. Febrile nonhemolytic reactions are diagnosed if there is an unexplained 1 C increase in temperature while the blood product is being infused. This can occur because of cytokine buildup in the transfused blood or by recipient antibodies activating donor white blood cells, resulting in cytokine release. TACO results when administration of blood products can result in acute pulmonary edema because of excessive fluid transfusion. The elderly, neonates, and patients with heart failure,
https://doi.org/10.1016/j.jradnu.2019.11.003 1546-0843/$36.00/Published by Elsevier Inc. on behalf of the Association for Radiologic & Imaging Nursing. All rights reserved.
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renal disease, and anemia are most susceptible to dyspnea secondary to volume overload. TRALI is defined as acute lung injury that occurs within 6 hr of blood product transfusion. This is a diagnosis of exclusion, as the lung injury cannot be attributed to other causes of lung injury, such as pneumonia. This is more often seen in blood products high in plasma content. The transfusion product contains antibodies that then activate the neutrophils causing the signs and symptoms of TRALI. The patient usually has a clinical condition where the pulmonary epithelium has become activated with increased numbers of neutrophils present (Vlaar et al., 2019). The chest radiograph and CAT scan will show pulmonary infiltrates similar in appearance to acute respiratory distress syndrome. Bacterial contamination is caused by administration of blood products contaminated with bacteria. This is most commonly seen in platelet transfusions. Anaphylactic reactions are severe allergic reactions caused by a patient antibody to a donor protein that activates cells such as mast cells and basophils, which then degranulate and cause the severe symptoms encountered (Reber, Hernandez, & Galli, 2017). Acute hemolytic reactions are caused by patient antibody reacting to donor red blood cell proteins, resulting in hemolysis of the donor cells. This usually is caused by ABO incompatibility.
Onset of Acute Transfusion Reactions Acute transfusion reactions typically occur during the first 24 hr after transfusion. Most occur during the transfusion itself. The typical time course for presentation of acute transfusion reactions is summarized in Figure 2. Common Symptoms of Transfusion Reaction Common symptoms that occur during transfusion reactions include (but are not limited to) fever, hypotension, rigors, urticaria, hypoxia, and dyspnea. The types of common acute transfusion reactions and their associated symptoms are summarized in Table 1. Fever, hypotension, and dyspnea are discussed further as they can be used to help distinguish between common acute transfusion reactions, which are summarized in Figure 3. Fever may indicate a transfusion reaction. It is normal to have slight temperature variations (± 0.5 C) while administering blood (Crookston et al., 2015). An increase in temperature of 1 C
Figure 1. Relative frequency of complications associated with blood transfusion. The approximate incidence is given per unit transfused. Note that some reactions are more likely to be associated with certain components (e.g., bacterial contamination / platelets; acute hemolytic reactions / RBC). The graph is not drawn to scale. Abbreviations: RBC ¼ red blood cell; TACO ¼ transfusion-associated circulatory overload; TRALI ¼ transfusion-related acute lung injury. Graphic design by Kimberly Crookston Hill. Reprinted with permission (Crookston et al., 2015).
Figure 2. Time course for the typical presentation of transfusion reactions. The bracket emphasizes those reactions that begin during transfusion or later on day 1. Refer to Table 1 for specific signs and symptoms associated with each reaction type. Abbreviations: TACO ¼ transfusion-associated circulatory overload; TRALI ¼ transfusionrelated acute lung injury; TA-GVHD = transfusion associated graft versus host disease. Graphic design by Kimberly Crookston Hill. Reprinted with permission (Crookston et al., 2015).
or more could indicate a simple febrile reaction or the more serious hemolytic or septic reactions. Hypotension may indicate a more serious, potentially lethal reaction, which includes acute hemolysis, anaphylaxis, bacterial contamination, and acute lung injury. Dyspnea during a transfusion may be the result of the patient's underlying condition, such as congestive heart failure. TACO is the most common reason for a transfusion recipient to become dyspneic although TRALI is also within the differential. It is very important to distinguish between TACO and TRALI, as TACO is treated with diuretics and diuretics can worsen TRALI (Crookston et al. 2015). Hives and/or itching are signs seen with the most common transfusion reaction, mild acute transfusion reaction. These symptoms are not restricted to mild acute transfusion reactions and can rapidly progress into anaphylactic reactions. It is difficult to distinguish at the time of onset of hives/itching whether this reaction will proceed to an anaphylactic reaction so the patient needs to be monitored closely.
Treatment of a Suspected Transfusion Reaction The single most important thing to do when a transfusion reaction is suspected is to stop the transfusion immediately and keep the line open. There are usually forms provided by the institution to document the transfusion reaction, with instructions about which post-transfusion blood specimens to draw for the blood bank investigation. Laboratory testing is helpful with diagnosing what caused the reaction. The blood bag, infusion set, and anything else attached to the set should be sent to the laboratory for further evaluation. Determining why the reaction occurred is very important, as it may affect treatment and whether the patient can receive blood products in the future. Furthermore, if the products were contaminated in any way, other blood components from that same donor need to be removed from the shelf. In general, once a transfusion is stopped, it should not be restarted. Treatment of the reaction depends on the type of reaction that is occurring. Diphenhydramine and acetaminophen are used for mild allergic and febrile nonhemolytic reactions. In more serious and
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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Table 1 Signs and symptoms typically seen during acute transfusion reactions Acute complications of transfusion Complication
Signs and symptoms
Mild allergic reaction Febrile nonhemolytic reaction Volume overload/transfusion-associated circulatory overload (TACO) Acute lung injury/transfusion-related acute lung injury (TRALI)
Urticaria and pruritis Fever and chills Dyspnea, orthopnea, tachycardia, congestive heart failure, headache Dyspnea, hypoxia, hypotension, can look similar to acute respiratory distress syndrome (ARDS) on imaging Findings of sepsis including rigors, fever, hypotension. Most commonly seen in platelet transfusions Respiratory distress, shock, hypotension Fever, chills, nausea, hypotension, back or chest pain, hematuria, shock
Bacterial contamination Anaphylaxis Acute hemolytic reaction
complicated cases, consulting an expert should be considered. In all cases of hemolytic transfusion reaction, baseline laboratory values should be obtained, with administration of intravenous (IV) fluids to protect the kidneys, as the increased free hemoglobin in the blood from red blood cell lysis may cause kidney damage. TACO may be treated with diuretics. TRALI is treated with oxygen and supportive care, which may include intubation. Bacterial contamination may require blood pressure support and antibiotics. Anaphylaxis is treated per hospital protocol, usually with epinephrine and diphenhydramine. It is controversial whether premedication with diphenhydramine and acetaminophen should be given to prevent mild transfusion reactions, as several controlled trials demonstrated that premedication does not prevent such reactions (Crookston et al. 2015). Introduction to radiological contrast media There are two basic types of iodine-based contrast: high osmolar and low osmolar. High osmolar contrast is rarely used anymore as it
has a significantly higher incidence of complications including a 6fold increase in contrast reactions. Higher incidence of renal toxicity is also associated with high osmolarity contrast media that has an osmolarity of 1,570 mosm/kg. Low osmolar nonionic iodine-based contrast is almost ubiquitously used today as it is associated with fewer reactions and less renal toxicity with an osmolarity of 290e672 mosm/kg and will be the subject of this discussion (Salijoughian, 2012). Iodine-based contrast is often used for computed tomography scans (CT scans) and during procedures performed in interventional radiology, cardiology, and gastroenterology. The volume administered during a CT scan varies from institution to institution, as there are weight-based and fixed contrast media dosing protocols. The volume of iodinated contrast used during interventional radiology, gastroenterology, and cardiology procedures varies widely and depends on the type and complexity of the procedure being performed. Reactions to IV iodinated contrast, whether it is used for a CT scan or for other procedures, have an incidence of 0.2e0.7%. Severe contrast reactions (e.g., anaphylaxis) occur in 0.1% of people receiving IV iodine contrast, with death occurring in approximately 1:170,000 receiving contrast injections (Beckett, Moriarity, and Langer, 2015). Acute reactions typically occur within 20e60 minutes of iodinebased administration of contrast media. Delayed reactions are those that occur outside of the 60-minute time interval. Risk factors for having a reaction to iodinated contrast media include previous reaction to iodinated contrast, other severe allergies, history of asthma, history of atopy (3- to 6-fold increase), history of cardiac disease, and a history of renal disease. Prior reaction to iodinated contrast media does not guarantee a future reaction but does increase the likelihood of a future reaction by 5- to 6-fold (Beckett, et al., 2015). Types of iodine-based contrast media reactions There are two basic types of reactions that occur with iodinebased contrast media: chemotoxic and allergic. Allergic reactions can further be broken down into true allergic reactions and allergiclike or anaphylactoid reactions (Bohm, Morelli, Nairz, Silva Hasembank Keller, & Heverhagen, 2017).
Figure 3. Transfusion reaction recognition at the bedside. Signs and symptoms help the clinical team differentiate a normal patient response to transfusion from a potential transfusion reaction. *The “normal” vital sign changes during transfusion are approximated for use as a “rule of thumb” to help in recognition of a possible transfusion reaction. When changes fall outside these parameters, special vigilance is needed to monitor for possible reactions. Abbreviations: TACO ¼ transfusionassociated circulatory overload; TRALI ¼ transfusion-related acute lung injury; T ¼ temperature; RR ¼ respiratory rate in respirations per minute (rpm); HR ¼ heart rate in beats per minute (bpm); BP ¼ either systolic or diastolic blood pressure in millimeters of mercury (mm Hg). Graphic design by Kimberly Crookston Hill. Reprinted with permission (Crookston et al., 2015).
Chemotoxic Reaction This is also known as physiologic type reaction. This type of reaction does not involve the immune system and is the body's response to a chemical in the system. The chemotoxic reaction is believed to be caused by a disruption of homeostasis of the body because of increased viscosity and osmolarity of the contrast as compared with serum. The higher osmolarity can cause fluid shifts,
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leading to cell dehydration. Chemotoxic reactions are, in general, more often seen after interventional procedures where large amounts of iodine-based contrast media may be used (Beckett et al., 2015). Chemotoxic reactions may be classified as mild, moderate, or severe. These may have a variety of symptoms including feeling of warmth, nausea, vomiting, vasovagal reaction, hypertension, headache, chest pain, and seizure. It is important to note that the feeling of warmth is not a true fever. These are further summarized in Table 2. Allergic Reaction True allergic reactions to iodinated contrast occur when the contrast molecule causes a release of the antibody, IgE. This causes a biochemical cascade that can ultimately lead to the signs and symptoms of anaphylaxis. To determine whether the patient is truly having an allergic reaction to iodine-based contrast media, a skin test can be performed; this is rarely performed, as true allergic reactions to iodinated contrast are rare. A positive skin test indicates that a true allergic reaction to iodinated contrast has occurred (Bohm, et al., 2017). These reactions have the typical signs and symptoms of anaphylaxis, including respiratory distress, shock, and hypotension (Brockow, et al., 2005). Allergic-Like Reactions These reactions are also known as anaphylactoid reactions in some literature. These are considered a pseudoallergy because IgE antibody is not released. Despite the name and the lack of antibody response, these reactions can be very severe, even life-threatening. Because these reactions are not antibody mediated, they can occur without prior exposure to iodinated contrast. It has been hypothesized that as the iodine-based contrast moves through the lungs, mast cells become activated, causing these cells to release a large amount of histamine into the blood. The large amount of histamine causes the symptoms that are commonly seen with anaphylactoid reactions, such as hives, dyspnea, hypertension, and hypotension. Other pathways are hypothesized to also become involved in these reactions, such as kinin and complement systems (Dillman, Trout, & Davenport, 2018). Allergic-like contrast reactions may be classified as mild, moderate, or severe. The symptoms include urticaria, pruritus,
hypertension, hoarseness, throat tightness, wheezing, hypoxia, and facial edema. These findings are further summarized on Table 2. Myths Regarding Iodine-Based Contrast Media Reactions It is important to dispel a couple of common myths involving iodine-based contrast media reactions. Concurrent seafood allergies, specifically shellfish allergies, do not increase iodine-based contrast media reactions. It is safe to give a patient with a seafood or shellfish allergy iodine-based contrast media (assuming they have not had a reaction to iodinated contrast media in the past). Topical iodine allergies also do not cross-react with iodinated contrast media allergies. In summary, as long as the patient has not had a previous iodine-based contrast reaction then it is safe to administer iodine-based contrast media to a patient with a topical iodine allergy or seafood allergy (Bohm, et al., 2017; Salijoughian, 2012).
Drug Contraindications Of note, patients who are taking metformin may require the drug to be held 48 hr after administration of iodinated contrast as this combination can potentially cause severe lactic acidosis (Baerlocher, Asch, & Myers, 2013). In general, patients with no evidence of acute kidney injury before the administration of iodinebased contrast do not require metformin to be withheld after contrast administration (Goergen, Rumbold, Compton, & Harris, 2010). Those patients who are known to have acute or chronic kidney disease before administration of metformin should hold the medication for 48 hr after administration of iodine-based contrast. Reinstitution is often only performed after renal function has been re-evaluated. Refer to the local institutional protocol, as these are general guidelines and may vary. Metformin is typically prescribed for diabetics to help control blood sugar. It has been proposed that metformin causes reduced gluconeogenesis in the liver, which then prevents uptake of lactate by the liver, leading to increased lactic acid within the blood stream. Any other process that can lead to increased lactic acid within the body can then potentially lead to lactic acidosis. Renal impairment can lead to decreased clearance of metformin from the body with the higher levels of metformin leading to further decrease in gluconeogenesis and increased lactic acid in the blood stream. There is potential that IV iodine-based contrast could cause transient decrease in renal function, leading to higher levels of
Table 2 Signs and symptoms typically seen during iodine-based contrast reactions Acute complications of iodine-based contrast reactions Physiologic type reaction
Symptoms
Mild
General: flushing, warmth, sneezing, rhinorrhea Cardiovascular (CV): mild hypertension Gastrointestinal (GI): mild nausea or vomiting Central nervous system (CNS): anxiety, vasovagal reaction requiring no treatment, headache CV: chest pain without EKG changes, hypertensive urgency GI: moderate nausea or vomiting CNS: vasovagal reaction requiring treatment CV: hypertensive crisis, arrhythmia, possible EKG changes CNS: seizures, unresponsive/unconscious
Moderate
Severe Allergic type reaction
Symptoms
Mild
General: urticaria, pruritus, rhinorrhea, sneezing, nasal congestion CV: mild hypertension GI: nausea, mild vomiting. General: generalized erythema, urticaria, pruritis, edema Pulmonary: hoarseness, throat tightness, possible mild hypoxia, wheezing General: Severe facial and laryngeal edema. Pulmonary: hypoxia CV: hypotension
Moderate Severe
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metformin in the blood, and potentially leading to lethal levels of lactic acid (Goergen et al., 2010). The following medications contain metformin; the generic name is followed by common brand name(s) in parentheses: metformin (Glucophage, Glucophage XR, Fortamet, Riomet, Glumetza); glyburide/metformin (Glucovance); glipizide/metformin (Metaglip); linagliptin/metformin (Jentadueto); pioglitazone/metformin (Prandimet); rosiglitazone/metformin (Avandamet); saxagliptin/metformin (Kombiglyze XR); sitagliptin/metformin (Janumet, Janumet XR). Recognition and treatment of iodine-based contrast reactions It is important to closely monitor vital signs during a suspected iodine-based contrast reaction, whether chemotoxic, allergic, or allergic-like. Unlike during blood transfusions, patients who are receiving iodinated contrast media may or may not be under careful vital sign monitoring. If an iodinated contrast reaction is suspected, particularly if it might be moderate or severe, then vital sign monitoring needs to be promptly initiated.
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diphenhydramine can be administered by mouth or intravenously. A nonsedating antihistamine such as fexofenadine can be considered for patients who may need to drive themselves home. Moderate/Severe Monitor vital signs and preserve IV access. Consider 25e50 mg of diphenhydramine (note that diphenhydramine may cause hypotension). Diffuse Erythema For all forms, preserve IV access, monitor vital signs, and administer oxygen. Normotensive with erythema Monitor the patient's vital signs. No other treatment is normally needed Hypotensive with erythema Administer IV saline rapidly. If profound hypotension or unresponsive to fluid resuscitation, then consider administering epinephrine and calling the emergency response team.
Management of Iodine-Based Contrast Reactions
Bronchospasm
Treatment and bedside management of iodinated contrast reactions depend on the presentation and the severity of the reactions that are occurring (Maddox, 2002; Morzycki, Bhatia, & Murphy, 2017). Alerting the clinical team and obtaining vital signs are key first steps. Maintaining the airway and placing the patient on oxygen should be performed for all moderate and severe reactions. Maintaining an IV line or obtaining new access is also critical for moderate and severe reactions. The patient may have stridor and/or expiratory wheezes in which case talking to the patient may make these symptoms more apparent. The patient may describe severe anxiety or crushing chest pain. Differentiating between physiologic, allergic, and allergic-like contrast reactions is not necessarily important at the time of presentation because treatment of the symptoms takes precedence. For any reaction that is deemed to originate from iodinated contrast media, it is critical to update the patient's chart to reflect the reactiondthis is typically listed in the allergy section. It is also important to list the symptoms that occurred during the reaction. This helps guide future decision-making if the patient needs iodinated contrast later, whether contrast may ever be given again, and whether pretreatment with diphenhydramine or steroids might be of benefit. Of note, steroids are not useful in acute treatment of any reaction. Steroids may be used to help prevent shortterm recurrence of an allergic-like reaction (Beckett, et al., 2015). If the patient starts showing symptoms of an acute reaction to iodinated contrast media during a procedure, then the risks and benefits of continuing the procedure must be weighed. Any severe reaction should cause the procedure to be terminated. A clinician may choose to treat mild and potentially moderate reaction symptoms using medications if a critical procedure is underway that cannot be halted.
For all forms, preserve IV access, monitor vital signs, and administer oxygen.
Hives
Hypertensive Crisis
Mild Scattered or transient hives often do not require any treatment. The patient may be observed and no intervention may be needed if the symptoms resolve. If symptoms persist, then 25e50 mg of
Preserve IV access, monitor vital signs, administer oxygen, and administer IV labetalol. The dose can be doubled every 10 minutes. Nitroglycerin may be used in lieu of labetalol. Administer a diuretic such as furosemide. Call emergency response team.
Mild Administer beta agonist inhaler and consider calling the emergency response team if the response to the inhaler in inadequate. Moderate Administer beta agonist inhaler. This can be repeated up to three times. Consider administering epinephrine and calling the emergency response team. Severe Administer epinephrine and IV fluids. If possible, administer beta agonist inhaler. Call the emergency response team. Laryngeal Edema Preserve IV access, monitor vital signs, administer oxygen, call the emergency response team, and administer epinephrine. Hypotension Preserve IV access, monitor vital signs, administer oxygen, elevate legs, and administer fluids (~1,000 mL in adults). If there is hypotension with bradycardia, then this is likely a vasovagal reaction. If the patient remains symptomatic despite the aforementioned measures, consider administering epinephrine. Consider calling the emergency response team.
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Pulmonary Edema Preserve IV access, monitor vital signs, administer oxygen, elevate head of bed (if possible), administer a diuretic such as furosemide, and call the emergency response team. Seizures Observe and protect the patient. Turn the patient on their side to avoid aspiration, observing cervical spine precautions if necessary and suction airway if needed. Preserve IV access, monitor vital signs, and administer oxygen. Call the emergency response team. If the seizure is unremitting then consider administration of a benzodiazepine such as lorazepam. Differentiating between radiologic contract reactions and transfusion reactions In acutely ill patients, blood products and iodine-based contrast media may sometimes need to be administered simultaneously or in close proximity to one another. For instance, an ICU patient may have just received blood products before being transported to radiology. The blood products and contrast media can both lead to adverse reactions. Rapid recognition of a potential reaction is critical to timely intervention to minimize patient harm. The key is to realize that a reaction is occurring and to take appropriate action. There are several signs and symptoms that can be seen in both iodinated contrast and transfusion reactions, such as hives, chills, dyspnea, and hypotension. Immediately, the acute symptoms need to be managed with a detailed investigation into what is causing the reaction. Acute iodine-based contrast reactions usually occur within 1 hr of administration. If it has been longer than 1 hr since contrast administration and blood products are concurrently being given then the reaction is more likely due to the blood. Blood products are also statistically more likely to cause a reaction, when compared with iodine-based contrast media. When a severe reaction occurs and the cause is in doubt (blood transfusion vs iodine-based contrast reaction), then reaching out to both a radiologist and transfusion specialist is warranted. The medical team can work with both experts to determine the cause of the reaction. Most of the reactions are treated symptomatically but TRALI needs to be identified quickly, as it is treated differently than other acute transfusion or iodinated contrast reactions (Crookston et al., 2015). Common Signs and Symptoms That May Be Seen in Transfusion and Iodine-Based Contrast Reactions Figure 4 illustrates signs and symptoms that may be seen in both transfusion and contrast reactions and the most likely causes. Hives and/or itching can be seen in mild acute transfusion reactions, mild and moderate allergic-like contrast media reactions, and mild physiologic contrast media reactions. These entities are treated the same despite their origin (e.g., consider administration of diphenhydramine). If blood is being administered, then stop the transfusion. The blood product and associated tubing should to be sent to the laboratory for further investigation until it is discovered whether the blood products or an iodinated contrast reaction caused the symptoms. Fever is seen almost exclusively with transfusion reactions. Patients with iodine-based contrast media reactions may experience flushing and warmth but do not typically have increased temperatures.
Figure 4. Recognition and differentiation of transfusion reactions and iodine-based contrast reactions at the bedside. Signs and symptoms help the clinical team to recognize reactions and to formulate a differential diagnosis of possible reactions types. Abbreviations: TACO ¼ transfusion-associated circulatory overload; TRALI ¼ transfusion-related acute lung injury; Rxn ¼ reaction. Graphic design by Kimberly Crookston Hill.
Chills may be seen with either mild or moderate physiologic contrast reactions or mild, moderate, or severe allergic-like contrast reactions as a nonspecific symptom. It can also be seen in acute transfusion reactions, especially with bacterial contamination. Bacterial contamination is most common in platelet transfusion and should be high on the differential with any signs of sepsis. If this occurs then stop the transfusion and the tubing and bag must be sent to the laboratory. Treat the symptoms as necessary. Hypotension is a nonspecific symptom that is seen in both iodinated contrast and acute transfusion reactions. Regardless of origin, hypotension is treated with fluids. Again, when any transfusion reaction is suspected, discontinue the transfusion and send the blood bag and administration set to the laboratory for further testing. Dyspnea is another nonspecific symptom that can be seen with either acute transfusion or iodinated contrast reactions. This is most common with severe allergic-like reactions and can be seen in acute hemolytic, TRALI, or TACO-type transfusion reactions. Determining the cause of dyspnea is crucial as these entities are all treated differently. Inspiratory or expiratory wheezes suggest an anaphylactic reaction and need to be treated appropriately, whether the reaction is caused by a transfusion or iodinated contrast reaction. Occasionally, iodinated contrast can be given in enough volume to give symptoms of volume overload in susceptible populations. This can be treated the same as TACO, with diuretics. Again, it is important to identify TRALI as it is not treated with any of the other previously described medications and can be exacerbated by diuretics (Vlaar et al., 2019). The other symptoms that are common in iodine-based contrast media reactions are not specific to these reactions but can occasionally overlap with symptoms of the patient's acute illness and unusual presentations of transfusion reactions. Conclusion Blood product transfusion and iodine-based contrast may need to be given in close proximity to one another in the acutely ill
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003
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patient. Both of these entities can cause a variety of reactions, some of which may be life-threatening. Basic knowledge of the most common types of reactions for both entities increases the likelihood of prompt identification of the reaction and initiation of proper treatment. Statistically, acute blood transfusions are more likely to occur than acute iodine-based contrast media reactions. Most reactions to iodinated contrast occur within 1 hour of administration. At bedside, it is critical to identify that a reaction is occurring, as most reactions, whether caused by a transfusion or from iodinated contrast media, are treated symptomatically. If a transfusion is running, then stop the transfusion immediately and keep the line open. The remaining blood that has not yet been administered needs to be saved to be taken to the laboratory for further testing. Vital signs must be monitored closely, with oxygen administration needed for most reactions. Once the patient is stabilized then a detailed investigation into the cause of the reaction needs to be initiated. There is significant overlap in the symptoms of both transfusion and iodine-based contrast media reactions that can make bedside identification difficult. In those cases, there will need to be communication between the medical team, transfusion service, and radiology to identify the cause of the reaction. Useful web links American College of Radiology Manual on Contrast Media: https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Con trast_Media.pdf European Society Of Urogenital Contrast Agent Guidelines: http://www.esur-cm.org/index.php/ Journal of Applied Radiology Review of common and uncommon contrast media reactions: https://appliedradiology.com/articles/ review-of-common-and-uncommon-contrast-media-reactions University of California, San Francisco Department of Radiology and Biomedical ImagingdManagement of Acute Reactions to Contrast Media in Adults: https://radiology.ucsf.edu/patientcare/patient-safety/contrast/iodinated/reactions-adults
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University of California, San Francisco Department of Radiology and Biomedical ImagingdTreatment of Acute Reactions to Contrast Media in Children: https://radiology.ucsf.edu/patientsafety/contrast/iodinated/reactions-children UpToDate ReviewdDiagnosis and treatment of an acute reaction to a radiologic contrast agent: https://www.uptodate.com/ contents/diagnosis-and-treatment-of-an-acute-reaction-to-aradiologic-contrast-agent
References Baerlocher, M.O., Asch, M., & Myers, A. (2013). Five things to know about…metformin and intravenous contrast. CMAJ, 185, E78. Beckett, K.R., Moriarity, A.K., & Langer, J.M. (2015). Safe use of contrast media: what the radiologist needs to know. Radiographics, 35, 1738-1750. Bohm, I., Morelli, J., Nairz, K., Silva Hasembank Keller, P., & Heverhagen, J.T. (2017). Myths and misconceptions concerning contrast media-induced anaphylaxis: a narrative review. Postgraduate Medical Journal, 129, 259-266. Brockow, K., Christiansen, C., Kanny, G., Clement, O., Barbaud, A., Bircher, A., et al. (2005). Management of hypersensitivity reactions to iodinated contrast media. Allergy, 60, 150-158. Crookston, K.P., Koenig, S.C., & Reyes, M.D. (2015). Transfusion reaction identification and management at the bedside. Journal of Infusion Nursing, 38, 104-113. Dillman, J.R., Trout, A.T., & Davenport, M.S. (2018). Allergic-like contrast media reaction management in children. Pediatric Radiology, 48, 1688-1694. Goergen, S.K., Rumbold, G., Compton, G., & Harris, C. (2010). Systematic review of current guidelines, and their evidence base, on risk of lactic acidosis after administration of contrast medium for patients receiving metformin. Radiology, 254, 261-269. Maddox, T.G. (2002). Adverse reactions to contrast material: recognition, prevention, and treatment. American Family Physician, 66, 1229-1234. Morzycki, A., Bhatia, A., & Murphy, K.J. (2017). Adverse reactions to contrast material: a Canadian update. Canadian Association of Radiologists Journal, 68, 187-193. Reber, L.L., Hernandez, J.D., & Galli, S.J. (2017). The pathophysiology of anaphylaxis. The Journal of Allergy and Clinical Immunology, 140, 335-348. Salijoughian, M. (2012) Intravenous radiocontract media: a review of allergic reactions. U.S. Pharmacist, 37, HS-14-HS-16. Retrieved from: https://www. uspharmacist.com/article/intravenous-radiocontrast-media-a-review-of-allergicreactions. Suddock, J.T., & Crookston, K.P. (2018). Transfusion Reactions. Treasure Island, FL: StatPearls. Vlaar, A.P.J., Toy, P., Fung, M., Looney, M.R., Juffermans, N.P., Bux, J., Bolton-Maggs, P., Peters, A.L., Silliman, C.C., Kor, D.J., & Kleinman, S. (2019). A consensus redefinition of transfusion-related acute lung injury. Transfusion, 59, 2465-2476.
Please cite this article in press as: Dumas NL, Crookston KP, Radiologic Contrast Reactions and Transfusion Reactions: Recognition, Differentiation, and Treatment, Journal of Radiology Nursing, https://doi.org/10.1016/j.jradnu.2019.11.003