Volume 88, Issue 11 , Pages 1465-1467, November 2007
Allergic Reactions to Gadodiamide Following Interventional Spinal Procedures: A Report of 4 Cases
Article Outline
Abstract
O’Donnell CJ, Cano WG. Allergic reactions to gadodiamide following interventional spinal procedures: a report of 4 cases.
Gadodiamide is currently considered a safe alternative for use in interventional spinal procedures in persons with a documented allergic response to iodine-based contrast dyes and with adequate renal function. The most common reactions to gadodiamide are nausea, emesis, and headache. These reactions usually are self-limited and are reported to occur in less than 1% of patients. We report the cases of 4 patients who developed an allergic reaction to gadodiamide, 3 of whom presented within the same week, after minimally invasive interventional spinal procedures at an outpatient private practice facility. Furthermore, 3 of the 4 patients had previously been exposed to gadodiamide during prior interventional spinal procedures without reaction, and the fourth patient had a reaction on the first exposure. The clinical presentation was manifested as a rash in 3 of the 4 patients, whereas the fourth patient experienced fevers and rigors along with rash. Because the injections of gadodiamide were not administered in succession, different vials of gadodiamide were used in each patient, and the injections were given by different clinicians at different spinal levels, we hypothesize that these patients experienced an allergic reaction, rather than contamination of the gadodiamide solution. These cases may call into question the safety of gadodiamide as an alternative contrast agent.
Key Words: Allergy, Case report, Gadolinium, Injections, epidural, Rehabilitation, Spine
TRADITIONALLY, GADOLINIUM-BASED radiographic contrast dyes have been used in patients with a previous allergic response to an iodine-based contrast dye and normal renal function. There are 5 gadolinium-based contrast agents commonly used in the United States: gadopentetate dimeglumnine (Magnevist), gadoteridol (ProHance), gadobente dimeglumine (MultiHance), gadodiamide (Omniscan), and gadoversetamide (Optimark).1 The reported rates of side effects and reactions to these agents have been low. The most common adverse reactions are nausea, headache, and emesis, which are reported to be at approximately 1% or less.1, 2
The following case reports are of 4 patients who underwent interventional spinal procedures in an outpatient, private practice setting using gadodiamide as a contrast agent secondary to a documented allergic reaction to an iodine-based contrast dye, and who subsequently developed allergic reactions to gadodiamide.
Case Descriptions
Case 1
Patient 1 was a 34-year-old man with no known medication allergies who underwent fluoroscopically guided zygoapophyseal joint corticosteroid injections secondary to low back pain using an iodine-based contrast dye. After the procedure, the patient developed an erythematous rash on the upper chest and right upper limb while in the recovery room (≈5min after the procedure). He did not have any urticaria, wheezing, or shortness of breath. He was treated with 50mg of diphenhydramine intramuscularly with resolution of his symptoms. On follow-up, the patient stated that his pain resolved 100% for approximately 1 week; however, it returned once he resumed his hobbies of soccer and Tae Kwon Do. The decision was made to progress with a second set of zygoapophyseal joint injections, this time using gadodiamide and an alcohol-based skin preparation. The patient underwent the second set of injections without complications. The patient received only temporary relief after the second injections and, despite a comprehensive course of physical therapy and medication management, he elected to go forward with diagnostic medial branch blocks prior to proceeding with medial branch thermal denervation. After the medial branch blocks, again using gadodiamide and an alcohol-based skin preparation, the patient developed a macular type rash on the anterior chest and abdomen prior to leaving the office, without any other symptoms. He was given 25mg of diphenhydramine intramuscularly and his symptoms resolved.
Case 2
Patient 2 was a 47-year-old woman with a documented iodine allergy who underwent an L5 transforaminal epidural steroid injection using gadodiamide and an alcohol-based skin preparation without complications. Her pain improved by 80% after the first injection and she elected to go forward with the second injection to further alleviate her pain. After the second injection, she experienced an episode of skin flushing, without urticaria or shortness of breath while in the postprocedure recovery room. She was immediately treated with 25mg of diphenhydramine intramuscularly, and her symptoms resolved without further incident. The patient underwent a third epidural injection using gadodiamide and an alcohol-based skin preparation approximately 4 weeks later; she was premedicated with 25mg of diphenhydramine by mouth approximately 1 hour before the procedure. She tolerated the procedure well, and did not have any evidence of an allergic reaction after the injection.
Case 3
Patient 3 was a 43-year-old woman without any history of drug allergies who underwent a left L4 transforaminal epidural steroid injection using an iodine-based contrast dye. The patient received partial relief, and elected to go forward with left L4 and 5 transforaminal epidural steroid injections about 1 month later. After a total of 3 epidural steroid injections, she received relief from her leg symptoms, but returned approximately 1 month later complaining of primarily left buttock pain. She underwent a fluoroscopically guided left sacroiliac joint injection, again using an iodine-based contrast dye. After this injection, the patient developed a macular rash along the “beltline,” without pruritus, urticaria, or shortness of breath prior to leaving the office. She was treated with 25mg of oral diphenhydramine and her symptoms resolved. She returned on follow-up stating that she did not receive any significant change in her pain, and the decision was made to go forward with diagnostic lumbar medial branch blockade. Because of the previous reaction, the procedure was performed using an alcohol-based skin preparation solution and gadodiamide. While in the postprocedure recovery room after the procedure, she developed a macular rash on the abdominal and lumbar regions without pruritus, urticaria, or shortness of breath. She was again treated with 25mg of oral diphenhydramine with resolution of her symptoms, and was discharged home in stable condition.
Case 4
Patient 4 was a 38-year-old woman without any known allergies who underwent right L4 and 5 transforaminal epidural steroid injections using an iodine-based contrast dye. Immediately after the injection, the patient was noted to have an erythematous rash at the lumbar paraspinal and anterior thoracic regions. She did not have any urticaria, wheezing, or shortness of breath. She was treated with 50mg of diphenhydramine intramuscularly with resolution of her symptoms. The patient responded well to the first injection; however, she returned approximately 8 weeks later complaining of a flare-up of her previous symptoms. She then underwent a right L4 transforaminal epidural steroid injection using gadodiamide and an alcohol-based skin preparation. The patient tolerated the procedure well, and noted resolution of her leg symptoms, but had persistent axial symptoms. The patient elected to go forward with a third epidural steroid injection. She again underwent right L4 and 5 transforaminal epidural steroid injections using gadodiamide and an alcohol-based skin preparation. While in the postprocedure recovery room, the patient developed a mild fever of 37.8°C (100°F), without other signs of an allergic response, including rash. She was monitored in the recovery room and was discharged home in stable condition. The patient telephoned the office about 4 days later stating that she had been experiencing intermittent fevers of 38.3°C (101°F), a chest rash, and an increase in her low back pain without any shortness of breath or neurologic deficit. She was immediately sent for a complete blood count with differential, an erythrocyte sedimentation rate, and was evaluated in the office. Her laboratory results were normal, without any signs of active infection. On examination, she was afebrile, but had a macular-papular rash on the anterior chest and back with associated dermatographism. Her injection site was nontender and well healed without signs of infection. Furthermore, her neurologic examination was normal. She was diagnosed with an allergic reaction to the gadodiamide contrast dye and was prescribed a tapering dose of the oral corticosteroid methylprednisolone (Medrol DosePack) with oral diphenhydramine as needed. On follow-up about a week later, she reported complete resolution of her symptoms.
Discussion
Our office uses multiple-use vials of gadodiamide as a contrast agent in approximately 30 to 40 cases per month. Prior to these cases, we had not experienced any allergic reactions associated with its use. Because 3 of 4 patients in our series had reactions to gadolinium within the same week in late August 2006, gadolinium contamination cannot be ruled out. There were, however, 5 other patients that week who received gadodiamide during an interventional spine procedure who did not have a postprocedure reaction, resulting in a 38% reaction rate for that week. This rate is far greater than the 1% published in the literature. Because of this, we have contacted the manufacturer of the agent, and, to date, they have not received any reports of similar episodes from other facilities, including vials from the lot number we used (no. 10355904). Furthermore, review of our records indicates that, aside from being performed in the same office with different vials of gadodiamide, these 3 patients’ procedures were not performed by the same clinician or in a sequential manner, arguing against an iatrogenic etiology, contamination of the anesthetic, or corticosteroid solutions. Although unlikely, gadodiamide contamination cannot be completely ruled out. To our knowledge, however, subsequent injections of patients at our facility using gadodiamide from the same lot number have not resulted in adverse reactions.
Despite these case reports, multiple studies have established that gadolinium-based contrast agents are a safe alternative to iodine-based contrast agents in patients without renal impairment, although variability exists in the rates of reactions among the different gadolinium-based formulations. Runge et al3 conducted a study in mice analyzing the potential for tissue toxicity as a result of extravasation of these agents. They found that gadopentetate dimeglumnine and gadoversetamide had a statistically higher rate of tissue necrosis and inflammation when compared with gadoteridol and gadodiamide, and are therefore more likely to produce an adverse reaction.
Likewise, a Chinese study4 compared the adverse systemic effects of intravenous gadopentetate (Magnevist) and gadodiamide (Omniscan) in 2049 subjects. Of the 2049 patients, 309 (15%) experienced some degree of side effects from the infusion. Of the patients who received gadopentetate, 22% had an adverse reaction, whereas only 12.6% of those receiving gadodiamide had an adverse reaction. An adverse reaction was defined as: “mild nonallergic reaction” (nausea or vomiting), “mild reactions resembling allergy” (skin irritation, erythema, or edema), “mild local reaction” (symptoms resembling thrombophlebitis), or “nonspecific adverse events” (headache, dizziness). When comparing the data for the reactions resembling an allergic response, only 1 patient in the gadodiamide group (.07%) had an allergic response, whereas 10 patients in the gadopentetate group (1.8%) had an allergic response.
In reference to its clinical applications, Murphy et al5 conducted a survey of neuroradiology fellowships in the United States and Canada regarding reactions to intravenous gadolinium-based contrast agents during magnetic resonance imaging (MRI) in patients with previous reactions to iodine-based agents. Of 72,275 patients injected with gadodiamide, they found 11 “nonallergic” reactions (nausea or vomiting) and 12 “mild reactions resembling allergy” (hives, diffuse erythema, skin irritation, or all 3) and no “moderate reactions resembling allergy” (respiratory symptoms) or “life-threatening reactions resembling allergy” (respiratory distress and facial or airway edema). That equates to .015% experiencing a nonallergic reaction and .016% experiencing a mild allergic response. A large, multicenter study6 was also conducted in Europe assessing the safety and efficacy profile of intravenous gadodiamide for use in MRI. A total of 2102 patients completed the study, and the most common adverse event was the sensation of local warmth or coldness at the site of injection (1.6%) followed by nausea at 1.1%. All other adverse reactions, including skin reactions (0.2%) and febrile episodes (.05%) were less than 1%.
It should be noted that the amount of contrast material used for MRI typically exceeds the amount injected for an interventional spinal procedure. For fluoroscopically guided spinal procedures, the typical dose is between 1 to 2mL, but the dose for MRI typically does not exceed 0.1mmol/kg (typically, 10mL), although doses up to 0.3mmol/kg have been given.1
A majority of the published studies on gadolinium reactions have been in reference to MRI studies, and few studies are available regarding reactions after interventional spinal procedures. Safriel et al7 published a consecutive case series of 127 patients undergoing interventional spinal procedures using gadodiamide secondary to a previous reaction to an iodine-based agent. They found no adverse reactions in this group of patients. They did add, however, that on assessing an additional 400 procedures, there were 2 patients who experienced seizures that necessitated hospital admission. These patients had undergone a cervical procedure within 1 hour of each other, and the possibility of gadodiamide contamination or intravascular lidocaine injection could not be ruled out by the authors. Despite these 2 reactions, none of the remaining 527 patients experienced any signs or symptoms of an allergic reaction after the use of gadodiamide. We therefore believe that this case report is among the first to report a series of allergic reactions after the administration of gadodiamide in interventional spine procedures.
Conclusions
In general, gadolinium-based contrast agents are considered a safe alternative for use in patients who have an allergy to an iodine-based contrast dye and normal renal function. Previous studies report allergic reactions to gadodiamide in less than 1% of patients. Despite this, we encountered 4 allergic reactions within a 4-week time span but have not noted any further reactions since then. All 4 were successfully treated as outpatients without sequelae. Because these allergic reactions were isolated to a short period of time and because we have not had any similar reactions, gadodiamide contamination cannot be completely ruled out. In the interest of patient safety, we therefore encourage any clinician experiencing similar episodes to report the event to the manufacturer of the contrast agent in an effort to minimize any future occurrences.
Acknowledgments
We thank Gregory Chapis, MD, Shawn Dalton-Bethea, MD, and Christopher Dankmyer, MD, for their clinical contribution to this report.
References
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- . Safety of magnetic resonance image contrast agents. J Magn Reson Imaging. 1999;10:477–484
- . Local tissue toxicity in response to extravascular extravasation of magnetic resonance contrast media. Invest Radiol. 2002;37:393–398
- . Incidence of adverse events after I.V. injection of MR contrast agents in a Chinese population: a comparison between gadopentetate and gadodiamide. Acta Radiol. 2000;41:662–666
- . Occurrence of adverse reactions to gadolinium-based contrast material and management of patients at increased risk: a survey of the American Society of Neuroradiology Fellowship Directors. Acad Radiol. 1999;6:656–664
- . Evaluation of the clinical safety of gadodiamide injection, a new nonionic MRI contrast medium for the central nervous system: a European perspective. Neuroradiology. 1996;38:537–541
- . Gadolinium use in spine procedures for patients with allergy to iodinated contrast—experience of 127 procedures. AJNR Am J Neuroradiol. 2006;27:1194–1197
No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any organization with which the author(s) is/are associated.
PII: S0003-9993(07)01339-1
doi:10.1016/j.apmr.2007.08.002
© 2007 American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
Volume 88, Issue 11 , Pages 1465-1467, November 2007
