It may be possible for patients with renal insufficiency, including those with end-stage kidney disease (ESKD), to undergo MRI using potentially safer preparations of gadolinium-based contrast agents (GBCAs) with “very low, if any” risk of the feared nephrogenic systemic sclerosis (NSF). 1
In contrast to the so called “linear” chelates of gadolinium (eg, gadodiamide, gadopentetate), “cyclic” GBCA’s (eg, gadoteridol) have not been clearly associated with NSF. 2 A Veterans Administration study involving gadoteridol identified no cases of NSF among the 141 patients on hemodialysis following 198 exposures. 2 In fact, the 2017 American College of Radiology (ACR) Manual on Contrast Media reports the risk of NSF with cyclic chelates as “very low, if any”. 1 Even when a cyclic GBCA is used in patients with ESKD, however, hemodialysis is recommended as soon as possible after MRI. 3
GBCAs are chelates with 2 major components: gadolinium and either a linear or cyclic ligand. Cyclic ligands bind to gadolinium more avidly, resulting in lower probability of circulating renally-cleared free gadolinium which when deposited in tissue is thought to potentially trigger NSF.2
Although NSF is characterized by progressive fibrosis of skin and soft tissue, it may involve multiple organs with an estimated 30% mortality rate. 4
Bonus Pearl: Did you know NSF is really a new disease, with no evidence of its existence before 1997?
- “Nephrogenic Systemic Fibrosis”. In ACR Manual on Contrast Media; Version 10.3; May 31, 2017. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf
- Reilly RF. Risk for nephrogenic systemic fibrosis with gadoteridol (ProHance) in patients who are on long-term hemodialysis. Clin J Am Soc Nephrol 2008;3:747-51. https://www.ncbi.nlm.nih.gov/pubmed/18287249
- Wang Y, Alkasab TK, Nari O, et al. Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines. Radiology 2011;260:105-111. https://www.ncbi.nlm.nih.gov/pubmed/21586680
- Schlaudecker JD, Bernheisel CR. Gadolinium-associated nephrogenic systemic fibrosis. Am Fam Physician 2009;80:711-14. https://www.aafp.org/afp/2009/1001/p711.pdf
Contributed by Richard Newcomb, MD, Mass General Hospital, Boston, MA.
Multiple choice (choose 1 answer)
1. Which of the following classes of antibiotics is associated with peripheral neuropathy?
2. The best time to test for inherited thrombophilia in a patient with acute deep venous thrombosis is…
a. At least 1 week after stopping anticoagulants and a minimum of 3 months of anticoagulation
b. Just before initiating anticoagulants
c. Once anticoagulation takes full effect
d. Any time, if suspected
3. All the following is true regarding brain MRI abnormalities following a seizure, except…
a. They are observed following status epilepticus only
b. They are often unilateral
c. They may occasionally be associated with leptomeningeal contrast enhancement
d. Abnormalities may persist for weeks or months
4. Which of the following is included in the quick SOFA criteria for sepsis?
a. Heart rate
b. Serum lactate
5. All of the following regarding iron replacement and infection is true, except…
a. Many common pathogens such as E.coli and Staphylococcus sp. depend on iron for their growth
b. Association of IV iron replacement and increased risk of infection has not been consistently demonstrated
c. A single randomized-controlled trial of IV iron in patients with active infection failed to show increased infectious complications or mortality with replacement
d. All of the above is true
True or false
1. Constipation may precede typical manifestations of Parkinson’s disease by 10 years or more
2. Urine Legionella antigen testing is >90% sensitive in legionnaire’s disease
3. Spontaneous coronary artery dissection should be particularly suspected in males over 50 years of age presenting with acute chest pain
4. Urine dipstick for detection of blood is >90% sensitive in identifying patients with rhabdomyolysis and CK >10,000 U/L
5. Diabetes is an independent risk factor for venous thrombophlebitis
Multiple choice questions:1=d; 2=a;3=a;4=d;5=c
True or false questions:1=True; 2,3,4,5=False
Yes it can, and the MRI abnormalities could represent seizure’s effects on the brain, not the seizure’s structural cause. Seizure-related MRI changes are often associated with status epilepticus, but have also been reported in complex partial status epilepticus.1,2
T2-weighted MRI images may show increased signal intensity at the cortical gray matter, subcortical white matter, or hippocampus. The MRI changes are unilateral about one-half of the cases, while in about 8% of patients leptomeningeal contrast-enhancement may be observed. Partial simple and complex seizures are associated with hippocampal involvement.3
The increased signal intensity following seizures is thought to be due to increased metabolism at the epileptogenic area, which in turn results in increased oxygen consumption, hypoxia, hypercarbia, lactic acidosis, and ultimately vasodilation and edema.
Reversibility of MRI changes following seizures has been noted between 15 and 150 days (average, 62 days). A structural abnormality is more likely the cause of a seizure when the MRI changes do not resolve during this period.3 Therefore, seizure-induced brain-MRI abnormalities remain a diagnosis of exclusion.
- Kim JA, Chung JI, Yoon PH, et al. Transient MR signal changes in patients with generalized tonicoclonic seizure or status epilepticus: periictal diffusion-weighted imaging. Am J Neuroradiol 2001; 22:1149–1160 http://www.ajnr.org/content/22/6/1149.long
- Henry TR, Brunberg DI, Pennell PB, et al. Focal cerebral magnetic resonance changes associated with partial status epilepticus. Epilepsia 1994; 35:35–41 http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.916.5237&rep=rep1&type=pdf
- Cianfoni A, Caulo M, Cerase A, et al. Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities. Eur J Radiol. 2013; 82(11):1964-72. http://www.ejradiology.com/article/S0720-048X(13)00271-4/fulltext
Contributed by Johan H.L. Boneschansker, MD, Mass General Hospital, Boston, MA.
Not as strong as one might expect with an increasing number of investigators questioning the causative role of IV contrast in precipitating CIN.
A 2013 meta-analysis involving observational—mostly retrospective— studies concluded that the risks of AKI, death, and dialysis were similar between IV contrast and non-contrast patients, including those with diabetes or underlying renal insufficiency1.
Two retrospective studies2,3 designed to control for a variety of factors that may affect the risk of AKI by propensity matching found divergent results with the larger and better designed study finding no significant difference in AKI between the 2 groups3. A 2017 retrospective cohort analysis of emergency department patients utilizing a similar propensity-score analysis also failed to find a difference in post-CT AKI between those receiving and not receiving IV contrast4.
Further shedding doubt on the role of IV contrast in causing AKI, a study involving patients with chronic kidney disease found no difference in the rates of excretion of 2 biomarkers of AKI (neutrophil gelatinase-associated lipocalin-NGAL, and kidney injury molecule-1-KIM-1) between patients with and without presumed CIN5. Some have even criticized experimental animal studies supporting the existence of CIN due to their poor applicability to human renal disease1.
This is not to say that IV CIN does not exist. Rather, we should keep an open mind about the pathophysiology and epidemiology of CIN. Stay tuned!
Fun pearl: Did you know that the first case of CIN was described in a patient with multiple myeloma undergoing IV pyelography (before the CT era)?
- McDonald JS, McDonald RJ, Comin J, et al. Frequency of acute kidney injury following intravenous contrast medium administration: a systematic review and meta-analysis. Radiology. 2013;267(1):119-128. https://www.ncbi.nlm.nih.gov/pubmed/23319662
- Davenport MS, Khalatbari S, Dillman JR, et al. Contrast material-induced nephrotoxicity and intravenous low-osmolality iodinated contrast material. Radiology. 2013;267(1):94-105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606541/pdf/121394.pdf
- McDonald RJ, McDonald JS, Bida JP, et al. Intravenous contrast material-induced nephropathy: causal or coincident phenomenon? Radiology 2013;267:106-18. https://www.ncbi.nlm.nih.gov/pubmed/23360742
- Hinson JS, Ehmann MR, Fine DM, et al. Risk of acute kidney injury after intravenous contrast media administration. Ann Emerg Med 2017; 69:577-586. https://www.ncbi.nlm.nih.gov/pubmed/28131489
- Kooiman J, van de Peppel WR, Sijpkens YWJ, et al. No increase in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion following intravenous contrast enhanced-CT. Eur Radio 2015;25:1926-34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457910/pdf/330_2015_Article_3624.pdf
Contributed by Ginger Jiang, Medical Student, Harvard Medical School
Water-soluble contrast agents (WCAs) (eg, meglumine diatrizoate or Gastrografin) are often ordered as the initial radiographic test for evaluation of esophageal perforation or leaks, followed by barium swallow if the test is negative because small leaks are better detected with the more radiopaque barium1. Such practice, however, is based on extrapolation of data on the deleterious effect of barium when extravasated into the peritoneal cavity, not the mediastinum1. In fact, clinical evidence linking mediastinitis to extravasated barium is lacking, and even in experimental studies, injection of barium into the mediastinum of cats have failed to cause clinically significant mediastinitis2.
When ordering a contrast swallow study, no medium should be considered totally safe or effective in detecting esophageal perforations or leaks and WCAs are no different. Potential disadvantages of WCAs include: 1. Inferior sensitivity (as low as 50%)—due to decreased radio-opacity—when compared to barium3; 2. Risk of pulmonary edema—occasionally lethal— when aspirated into the lung due to high osmolality (analogous to salt water drowning) and intense inflammatory reaction4,5; 3. Contraindication in the setting of tracheoesophageal fistula,6; 4. Risk of serious allergic reaction due to reabsorption of iodinated compounds1; and 5. Added exposure to radiation and cost of testing when the swallow study is repeated with barium. For these reasons, the standard practice of an initial WCA followed by a barium swallow`study if the former is negative, has been questioned, with some centers foregoing the WCA study altogether in favor of barium swallow in certain patients 1,6.
In short, when evaluating for esophageal perforation, WCAs should not categorically be considered a “better” or “safer” alternative to barium; in certain situations, barium may be the preferred agent. When in doubt, input from a thoracic surgeon is recommended.
- Gollub MJ, Bains MS. Barium sulfate: a new (old) contrast agent for diagnosis of postoperative esophageal leaks. Radiology 1997;202:360-62. https://www.ncbi.nlm.nih.gov/pubmed/9015057
- James AE, Montali RJ, Chaffee V, et al. Barium or gastrografin: which contrast media for diagnosis of esophageal tears? Gastroenterology 1975;68:1103-1113. https://www.ncbi.nlm.nih.gov/pubmed/1126592
- Berry BE, Ochsner JL. Perforation of the esophagus: a 30 year review. J Thorac Cardiovasc Surg 1973;65:1-7. http://www.jpedsurg.org/article/0022-3468(73)90248-0/abstract
- Trulzsch DV, PenmetsaA, Karim A, et al. Gastrografin-induced aspiration pneumonia: A lethal complication of computed tomography. South Med J 1992;85:1255-56. https://www.ncbi.nlm.nih.gov/pubmed/1470976
- Tuladhar R, Patole S, Whitehall J. Gastrografin aspiration in a neonate with tracheoesophageal fistula. J Paediatr Child Health 2000; 36:94-6. https://www.ncbi.nlm.nih.gov/pubmed/10723703
- FDA https://www.drugs.com/pro/gastrografin.html.
- Roh S, Iannettoni MD, Keech JC, et al. Role of barium swallow in diagnosing clinically significant anastomotic leak following esophagectomy. Korean J Thorac Cardiovasc Surg 2016;49:99-109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825910/pdf/kjtcv-49-099.pdf
The nonadhesive backing of some medicated or transdermal patches (TPs) contain aluminum or other metals that can become heated during an MRI1. FDA is aware of skin burns at the patch site in several patients wearing an aluminized TP during an MRI2.
The following TPs have been reported by the FDA to have aluminized backing: Androderm (testosterone transdermal system); 2. Catapres-TTS (clonidine transdermal system); 3. Nicoderm (nicotine transdermal system); 4. Nicotrol (nicotine transdermal system); 5. Prostep (nicotine transdermal system);6. Habitrol (nicotine transdermal system); 7. Nicotine transdermal system (generic nicotine transdermal system); 8. Transderm Nitro (nitroglycerin transdermal system); 9. Trasnsderm Scop (scopolamine transdermal system).
Other TPs that have metal backing but not necessarily carrying FDA warning include Flector (diclofenac), estradiol, Duragesic (fentanyl), Synera (lidocaine and tetracaine), methyl salicylate and menthol (over the counter), Oxytrol (oxybutynin), Exelon (rivastigmine), Neupro (rotigotine), and Emsam (selegiline)3.
In short, it is advisable that TPs with metal backing (either listed above or others) be removed prior to MRI.
- Kuehn B. FDA warning: remove drug patches before MRI to prevent burns to skin. JAMA. 2009;301:1328
- https://www.accessdata.fda.gov/scienceforums/forum06/k-26.htm , accessed April 19, 2017.
- http://www.pharmacytimes.com/contributor/alexander-kantorovich-pharmd-bcps/2016/08/transdermal-patches-that-must-be-removed-before-mri , accessed April 19,2017.
It cannot be overemphasized that up 50% of patients with spinal epidural abscess (SEA) have no known risk factors, one-half may have no fever, and 20-40% lack leukocytosis1. In fact, the “classic triad” of back pain, fever, and neurological deficits is found only in the minority of patients! No wonder that up to 75% of patients SEA are misdiagnosed on their initial healthcare encounter1!
Potential “red flags” for infectious causes of low back pain include age >50 y, night pain, unremitting pain even when supine, duration > 6 weeks, fever, chills, night sweats, weight loss, conditions associated with Staphylococcus aureus bacteremia (eg intravenous drug use), incontinence, saddle anesthesia, and severe or rapidly progressive neurologic deficits1,2.
ESR and C-reactive protein (CRP) are almost uniformly elevated in SEA1 and can serve as a good starting point in excluding this condition when in doubt. In patients ≥50 y of age with low back pain, obtaining ESR routinely has been suggested for detection of systemic disease (eg cancer, infection)3. Similarly, in a recent algorithm of severe back pain, routine measurements of ESR and CRP, even in the absence of any neurological findings, has been recommended1; elevation of either may necessitate consideration of MRI.
- Bond, A, Manian FA. Spinal epidural abscess: a review with special emphasis on earlier diagnosis. BioMed Res International 2016; https://www.hindawi.com/journals/bmri/2016/1614328/http://dx.doi.org/10.1155/2016/1614328
- Della-Giustina. Acute low back pain: recognizing the “red flags” in the workup. Consultant 2013;53:436-440. http://www.consultant360.com/article/acute-low-back-pain-recognizing-%E2%80%9Cred-flags%E2%80%9D-workup
- Jarvik JG, Deyo RA. Diagnostic evaluation of low back pain with emphasis on imaging. Ann Intern Med 2002;137:586-597. http://annals.org/aim/article/715687/diagnostic-evaluation-low-back-pain-emphasis-imaging
Disclosure: The author of this post (FAM) also coauthored reference 1.
Patients with shellfish allergy appear not to have a significantly higher rate of allergic reactions to iodinated contrast media compared to patients with history of atopy, such as asthma or other food allergies 1,2. When true shellfish allergy occurs, it is caused by an immunological reaction to the protein, not iodine, content of the food ingested. “Iodine allergy” cannot exist because iodine is found throughout our bodies and is essential to life.
The typical IV contrast-related adverse reaction is caused by non-IgE-mediated mast cell and basophil degranulation due to the high osmolality of these agents. Because the resultant “anaphylactoid” reaction is not associated with prior immune system memory, its risk is not increased by previous exposure to IV contrast. Premedication with corticosteroids and diphenhydramine may be effective in reducing the risk of such reactions, but is not routinely recommended in patients with isolated history of shellfish allergy2.
- Schabelman E, Witting M. The relationship of radioconstrast, iodine, and seafood allergies: a medical myth exposed. J Emerg Med 2010;39: 701-707.
- Westermann-Clark E, Pepper AN, Talreja N, Lockey RF. Debunking myths about “allergy” to radioconstrast media in an academic institution. Postgrad Med 2015;127:295-300.