New Canadian guidance for contrast media hypersensitivity reactions

A joint collaborative working group of the Canadian Association of Radiologists and the Canadian Society of Allergy and Clinical Immunology has issued practice guidance and consensus-based recommendations on hypersensitivity reactions to contrast media.Contrast media, including iodinated contrast media and gadolinium-based contrast agents, are commonly administered products with excellent safety profiles. However, some patients may experience a hypersensitivity reaction following intravenous administration. These reactions can be immediate or delayed, and range from mild (e.g., urticaria) to severe (e.g., anaphylaxis). Uncertainty exists regarding the safety of a repeat contrast media injection in patients with a history of a hypersensitivity reaction, and the efficacy of premedication in preventing future reactions. Emerging evidence suggests that longstanding pretreatment protocols involving diphenhydramine and corticosteroids are ineffective, have the potential for side effects and other harms, and their use is based on weak and outdated evidence. Although withholding intravenous contrast media altogether will ensure there will be no hypersensitivity reaction, doing so can substantially limit the diagnostic performance of computed tomography (CT) and magnetic resonance imaging (MRI).The new guidance document discusses five main issues related to contrast media hypersensitivity:Provides an overview of the epidemiology, physiology, risk factors, and types of hypersensitivity reactions to contrast mediaOutlines the evidence for pretreatment strategies that minimize the risk of a breakthrough hypersensitivity reaction for iodinated contrast media and gadolinium-based contrast agentsReviews the allergy investigations used to evaluate patients with a history of severe hypersensitivity reactionProvides an overview of existing guidelinesAppraises the evidence and establishes management recommendations (based on consensus).Reactions to contrast mediaThere are two main types of reactions to contrast media:Physiologic (or chemotoxic) reactions are most common. They are concentration- and dose-dependent side effects related to the specific molecular attributes of the medium. They may include vasovagal reaction, altered taste sensation, restlessness, headache, nausea, dizziness and paresthesia. Patients may experience warmth, cold or pain at the injection site. These reactions are usually self-limiting, but cardiotoxicity, neurotoxicity and nephrotoxicity may occur rarely.Hypersensitivity reactions, which are less common, are acute or immediate hypersensitivity reactions occurring within one hour of exposure and leading to symptoms ranging from mild urticaria to anaphylaxis. Delayed hypersensitivity reactions occur hours to days after exposure; they are usually mild and typically manifest as isolated skin reactions (e.g., a maculopapular exanthem). However, severe cutaneous reactions (e.g., generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms [DRESS], and Stevens-Johnson syndrome/toxic epidermal necrolysis [SJS/TEN]) can occur rarely.Note that hypersensitivity reactions to iodinated contrast media do not occur secondary to iodine, but rather to the contrast molecule itself. Therefore, the term “allergy to iodine” in reference to contrast media hypersensitivity reactions should not be used. Recommendations for contrast media hypersensitivity reactions:Document the dose and precise name of any contrast media in the patient’s electronic health record. If a patient experiences a hypersensitivity reaction, document the precise name of the offending contrast agent in the patient’s radiology report, which is also sent to the referring healthcare provider. Record the onset and nature of the reaction, as well as treatment provided.Patients should only be considered at risk for a hypersensitivity reaction if they had a previous hypersensitivity reaction to the same type of contrast agent. Evidence is insufficient to support routine screening of other risk factors. It is important to distinguish between a true hypersensitivity reaction and a physiologic reaction.For patients with a history of a mild, moderate or severe hypersensitivity reaction to an iodinated or gadolinium-based contrast agent, switching to a chemically different contrast agent is the single best protective measure to avoid a breakthrough reaction. If a patient develops a mild or moderate reaction after contrast switching, a third agent should be administered.If a patient has a history of a hypersensitivity reaction to an iodinated contrast media, but the offending agent is unknown, management is based on the date of the reaction (i.e., before or after the year 2000; see algorithm in the guidance document for details).In patients with a history of hypersensitivity reaction to low-osmolality iodinated contrast media, premedication with a corticosteroid is not supported by high quality research and is not recommended.In patients with a history of hypersensitivity reaction to gadolinium-based contrast agents, premedication with a corticosteroid is not recommended. Evidence supporting corticosteroid premedication to prevent a breakthrough reaction is mixed, but overall shows little benefit, with risk of potential harm.Second-generation antihistamines (e.g., cetirizine, desloratadine, fexofenadine, loratadine) can protect patients with a history of mild hypersensitivity reaction from a breakthrough reaction. The added benefit of an antihistamine after contrast switching is less clear and can be considered optional. Ideally, an oral second-generation antihistamine should be given at least one hour before initiation of contrast. First-generation antihistamines (e.g., chlorpheniramine, diphenhydramine, doxepin, hydroxyzine) can cause adverse effects, including sedation, poor sleep quality, cardiac toxicity, respiratory depression, coma and death. They are no longer recommended for use. Second-generation antihistamines minimally cross the blood-brain barrier, have no anticholinergic effects, and have significantly improved cardiac side effects.Currently, evidence is insufficient to recommend one low-osmolality contrast media product over another to reduce hypersensitivity reactions. Emerging evidence suggests that contrast switching may be guided by the molecular structure of an agent; however, evidence is insufficient to make specific recommendations at this time.Some evidence suggests differences in hypersensitivity reactions for different gadolinium-based contrast agents, but these differences are small and the overall risk of hypersensitivity reactions to gadolinium-based contrast agents is very low. The optimal choice of gadolinium-based contrast agent should be based on other factors, including cost, clinical indication and T1 relaxivity.For patients with a history of anaphylaxis to contrast media, the risk of a breakthrough reaction can be limited by switching to a different imaging modality, if diagnostically acceptable. If not, switching to a different contrast agent is recommended. The patient should be monitored during and after the contrast media injection. Premedication is not recommended.Once a patient who experiences anaphylaxis is stabilized, collection of serum tryptase may help to determine if the reaction was an immediate hypersensitivity reaction. Collect serum tryptase 30–120 minutes after the onset of symptoms. Consider referring to an allergy specialist, when possible.For patients with a history of hypersensitivity reaction to nonvascular contrast, contrast switching without premedication is recommended for future administrations of nonvascular or vascular contrast. Based on a lack of evidence and overall rarity of these events, expert consensus recommends against a pre-medication protocol.Patients should not be instructed to fast prior to receiving intravascular contrast media, unless required for the specific imaging examination (e.g., CT or MR enterography).The guidance document includes two algorithms (flowcharts) for minimizing the risk of a breakthrough reaction in patients with a history of hypersensitivity reaction to a known iodinated contrast medium or gadolinium-based contrast agent, and unknown iodinated contrast medium. The working group hopes that the recommendations in the guidance document will assist healthcare providers with updating departmental policies and protocols for contrast media hypersensitivity reactions.Reference:Byrne A, Macdonald B, Kirkpatrick IDC, et al. CAR/CSACI practice guidance for contrast media hypersensitivity. Can Assoc Radiol J 2025; published online Jan. 11, 2025. (accessed January 20, 2025).

New Canadian guidance for contrast media hypersensitivity reactions

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