Breakthrough Hypersensitivity Reactions to Gadolinium-based Contrast Agents and Strategies to Decrease Subsequent Reaction Rates: A Systematic Review and Meta-Analysis

Abstract

EVIDENCE-BASED PRACTICEG adolinium-based contrast agents (GBCAs) have been used clinically for decades and have an excellent safety record (1-3). Immediate hypersensitivity reactions to GB-CAs remain uncommon, estimated by meta-analysis to be approximately nine per 10 000 administrations, with severe reactions occurring in approximately five per 100 000 administrations (4). Limited studies have evaluated repeat GBCA administration in patients with a prior hypersensitivity reaction to a GBCA. The efficacy of corticosteroid premedication with or without antihistamines prior to repeat GBCA exposure remains unproven. Although commonly performed in clinical practice, the rationale for premedication prior to repeat GBCA administration is extrapolated from studies evaluating iodinated contrast media (5). Breakthrough reactions are immediate hypersensitivity reactions occurring despite appropriately dosed corticosteroid premedication. These reactions occur in up to one-third of patients in individual series that have studied GBCAs (6-8). Breakthrough reactions to GBCAs usually occur with the same severity as the original or index reaction, but escalation of breakthrough reaction severity to a GBCA has been reported (6-8). In patients with a prior severe hypersensitivity reaction to a GBCA, re-exposure to a GBCA (even with corticosteroid premedication) is contraindicated by the American College of Radiology (ACR) (9).

Hypersensitivity to Gadolinium-Based Contrast Media

“…It does not appear that premedication with corticosteroids prevents a future reaction. A 2019 systematic review and meta-analysis sought patients with immediate reactions to GBCAs who were undergoing repeated administration of GBCAs ( 40 ). The study concluded that in patients with a history of immediate reaction to GBCA, the repeated HRs to the same GBCA may occur in ~39%, despite the use of adequate premedication with corticosteroids.…”

Statement of the German Roentgen Society, German Society of Neuroradiology, and Society of German-speaking Pediatric Radiologists on Requirements for the Performance and Reporting of MR Imaging Examinations Outside of Radiology

“…The occurrence of allergic reactions depends on the type of contrast agent used, age, sex and admission status of the patients [13,14]. Patients who have already had allergic reactions to gadolinium (Gd)-based contrast agents are also at high risk (approximately 39 %) for a further allergic reaction with subsequent contrast agent applications, even with drug preparation [15]. Incorrect preparation of the intravenous injection of the contrast agent, which is usually applied by an injector, can lead to incorrect injections outside the vessel (so-called extravasations), the consequences of which can range from temporary pain to necrosis and permanent disability [16].…”

“…Bei Patienten, die bereits allergische Reaktionen auf Gadolinium (Gd) -basierte Kontrastmittel aufwiesen, besteht zudem ein hohes Risiko (ca. 39 %) auf eine weitere allergische Reaktion bei folgenden Kontrastmittelapplikationen, selbst bei medikamentöser Vorbereitung [15]. Eine fehlerhafte Vorbereitung der intravenösen Injektion des in der Regel maschinell applizierten Kontrastmittels kann zu Fehlinjektionen außerhalb des Gefäßes (sog.…”

Prevention of Allergic-like Reactions at Repeat CT: Steroid Pretreatment versus Contrast Material Substitution

“…However, the efficacy of this pretreatment has been questioned because most previous steroid studies have included highosmolarity ICMs that are no longer commonly used in clinical practice and had a higher rate of acute reactions than studies using low-and iso-osmolarity ICMs (4-10) and because previous studies have frequently included both high-risk and average-risk (ie, no previous ICM reaction) patients. Furthermore, breakthrough repeat reactions still occur in patients premedicated with a steroid at a rate of 2%-39% (11)(12)(13). As such, it is unclear whether steroid premedication remains a useful and effective means of preventing repeat allergic-like reactions in high-risk patients.…”