A Case Report on a Severe Anaphylaxis Reaction to Gadolinium-Based MR Contrast Media

Since the approval of gadolinium-based magnetic resonance (MR) contrast media by the U.S. Food and Drug Administration three decades ago, MR was thought to be a safer alternative for patients who are allergic to iodinated contrast media for computed tomography (CT) scan (1). Despite their relative safety profile, immediate hypersensitivity reactions to gadolinium-based MR contrast media are an area of pressing concern in clinical practice (2). Previous studies investigated the safety of MR contrast media and reported an incidence of acute adverse reactions in the range of 0.17% to 2.40%, which is much lower than that after the use of low-osmolar nonionic iodinated contrast media for CT (3). The incidence of severe acute adverse reactions to gadolinium-based MR contrast media is reported to be even lower, in the range of 0.002% to 0.01% (1, 2, 3, 4, 5). Here we report a case of a severe immediate adverse reaction to MR contrast media in order to inform the readers about the diagnosis and proper management of a severe anaphylaxis adverse reaction associated with the use of gadolinium-based MR contrast media. This case report was approved by the Institutional Review Board of our institution, and the requirement for obtaining informed consent was waived.

A 66-year-old woman was diagnosed with lacunar infarction involving the right thalamus in 2003, and she was being followed up at the neurology department of our hospital. She also had a history of left thyroid lobectomy in 1994 and was on medication for tension-type headache, hypertension, and hypercholesterolemia. Her medication list included the following drugs: atorvastatin, atenolol, aspirin, tibolone, and ibuprofen/arginine. Previously, the patient had undergone five CT examinations of the chest and kidneys from 2005 to 2013 using various types of contrast media including iopromide (Neovist®, Daewoong Pharma, Seoul, Korea) in 2013 and iopamidol (Pamiray®, Dongkook Ph-arma, Seoul, Korea) in 2012. The specific names of low molecular non-ionic iodinated contrast media used for CT examinations in 2005, 2010, 2011 were not documented. She had also undergone three MR examinations during the past 12 years, but none of them were performed with intravenous administration of gadolinium contrast media–two were non-contrast MRs and the other was MR arthrography. She denied any history of allergic reaction during previous examinations using contrast media.

The patient was scheduled for brain MRI and MRA and received 6 mL of gadobutrol (Gadovist®, Bayer Schering, Berlin, Germany). The timeline of the patient's clinical course is depicted in Fig 1. Three minutes after the injection, the patient started exhibiting a generalized tonic-clonic type seizure with upward deviation of both eyes and unconscious voiding. She also lost consciousness but soon recovered it within a few minutes. However, she showed delirious features and complained of an extreme urge to defecate. Her blood pressure dropped from the baseline level of 139/71 mm Hg to 90/40 mm Hg eight minutes after the injection. Considering the marginal range of blood pressure, 4 mg of chlorpheniramine was administered. Her blood pressure remained at 90/50 mm Hg with O₂ saturation of 95% eighteen minutes after the injection. The patient was transferred promptly to the emergency room under close monitoring. After transfer to the ER department, her systolic blood pressure dropped to 60 mm Hg, and 0.1 mg of 1:10000 epinephrine was administered via the intravenous route. After temporal recovery of the blood pressure to 119/99 mm Hg, it fell again to 70/41 mm Hg with a heart rate of 44 bpm, and 0.3 mg of 1:1000 epinephrine was administered intramuscularly. Her blood pressure still remained at 66/51 mm Hg. Therefore, continuous infusion of 8 mg of norepinephrine and 92 mL of 5% dextrose water at 6 cc/hr was started. Then, 0.1 mg of 1:10000 epinephrine was administered again via the intravenous route. Continuous infusion of norepinephrine was stopped once the blood pressure had stabilized. Approximately two hours after the seizure, her blood pressure was steady at 120/70 mm Hg with O₂ saturation of 98%. The patient was placed on close observation overnight in the ER department and discharged the next day without any sequelae.

Fig. 1
Timeline of the patient's clinical course including clinical events, medication and vital signs. bpm = beats per minute, Chlor = chlorpheniramine, Epi = epinephrine, ER = emergency room, HR = heart rate, NE = norepinephrine, PD = prednisolone, SBP = systolic blood pressure, Sz = seizure

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The gadolinium-based MR contrast media have been considered safer compared to their counterparts used for CT scan; thus, MR imaging has been widely utilized for patients who are allergic to iodinated contrast media used for CT scan. Historically, the rate of acute adverse reactions was reported to be in the range of 5% to 15% with the use of high-osmolar contrast media for CT (4). With the advent of low-osmolar contrast media, the rate of acute adverse reactions dropped significantly to 3.1% (4). The incidence of acute hypersensitivity reactions to gadolinium-based MR contrast media is reported to be much lower than that after the use of CT contrast media, in the range of 0.17% to 2.40% (3). However, with the increasing number of contrast-enhanced MR examinations being performed these days, there has been a rising concern about acute adverse reactions after the use of MR contrast media. Although most adverse reactions to MR contrast media are mild, a severe anaphylaxis reaction can occur, as seen in our case. According to our unpublished data, the incidence rate of severity of adverse reactions to MR contrast media during the one-year period, from February 2014 to January 2015, at our institution is 0.390%, with 149 cases out of 38168 cases that underwent MR examinations showing adverse reactions. The number of mild, moderate and severe adverse reactions during this period was 132 (0.346%), 16 (0.042%), and 1 (0.003%), respectively. These findings are in accordance with previous studies, which reported an incidence of adverse reaction rates in the range of 0.17% to 2.40% (3) and an incidence of severe adverse reactions in the range of 0.002% to 0.01% (1, 2, 3, 4, 5).

Due to the rarity of adverse reactions to MR contrast media, the contributing risk factors are not well understood, although various factors including female sex, previous allergic reaction to MR contrast media, history of asthma and higher creatinine levels are suggested (4). Dillman et al. (1) reported that although the difference is statistically insignificant, female patients experienced more acute allergic-like reactions, while Jung et al. (4) reported that the proportion of male patients experiencing immediate hypersensitivity reactions increased as the severity of the reactions increased. Additionally, a history of asthma and various allergies are suggested to be the risk factors for adverse reactions (6, 7). A previous study also indicated that the creatinine level tended to be higher in patients with more severe immediate hypersensitivity reactions (4). However, our patient did not have asthma or any type of allergies and the creatinine level was 0.75 mg/dL, which is far below the reported value of around 1 mg/dL.

Management of moderate to severe acute adverse reactions to gadolinium-based contrast media is similar to management of moderate to severe acute adverse reactions to iodinated contrast media (8). Management depends on the type of acute adverse reaction and it has been well-summarized in several guidelines including those from the American College of Radiology (ACR) and the European Society of Urogenital Radiology (ESUR) (9, 10). To briefly summarize the management, a mild or moderate adverse reaction should be treated according to the specific symptoms: antiemetics for gastrointestinal symptoms such as nausea and vomiting, β₂ agonist inhaler for bronchospasm, and antihistamine for cutaneous manifestation. However, immediate administration of epinephrine is the mainstay for the management of most types of severe adverse reactions, including hypotension, diffuse erythema, bronchospasm, laryngeal edema, unresponsiveness and pulselessness. Epinephrine 1:1000 dilution for intramuscular administration or epinephrine 1:10000 dilution for intravascular administration are proposed in the ACR guideline (9), whereas only 1:1000 epinephrine intramuscular administration is suggested in the ESUR guideline (10). Intramuscular administration seems to be more practical in the clinical setting of a radiology department, considering the side effects of intravenously administered epinephrine. Side effects including pulmonary edema, seizures/convulsions, hypoglycemia, and panic attack sh-ould be managed accordingly. Steroids can be given to prevent a delayed rebound reaction (9).

On retrospective review of the case, it was observed that some aspects of the management did not comply with the current gui-deline. Although the attending doctor considered the blood pressure of 90/50 mm Hg as a marginal level, epinephrine should have been administered sooner considering other associated symptoms such as loss of consciousness. In addition, epinephrine can be given either intravenously or intramuscularly. However, no time should be wasted in trying to establish the intravenous route if it is not readily available, and intramuscular injection is preferred considering the possible side effects of intra-venously administered epinephrine. Lastly, more detailed moni-toring of the patient's vital signs was necessary, especially for a severe anaphylaxis reaction.

Another consideration in acute adverse reactions related to MR contrast media is a longer MRI scan time. Contrary to CT, a longer scan time is required after administration of contrast media, which means that an acute adverse reaction can occur while patients are lying on the table for imaging. Radiologists and radiologic technicians should be aware of this and should monitor patients with monitoring devices while performing post-contrast MRI, because early detection is essential to proper management.

As demonstrated in our case, although rare, acute adverse reactions to MR contrast media do occur and severe reactions can be life-threatening. Radiologists should be aware of the potential adverse reaction to gadolinium-based contrast media and should be educated and prepared for the management of an adverse reaction.