MR Gadolinium Contrast PRINT

Uniform Guidelines for Use of Gadolinium-Based Contrast Agents 

Objective: Provide consistent guidelines for the administration of gadolinium-based contrast agents (GBCA) while maintaining the balance between high quality diagnostic studies and reducing patient risk. It is important to note that these are guidelines only – they are not strict protocols. Physicians are encouraged to assess each patient in light of the clinical situation and apply these guidelines or employ alternative methods as deemed appropriate by the monitoring/treating physician according to his/her clinical judgment. Special considerations for breastfeeding, pregnant women, and pediatric patients are included at the end of this document.

Facility and Staff: Staff should be prepared to identify and respond to contrast reactions and understand the facility processes for requesting additional help and/or emergency personnel. All patients receiving GBCA should be offered a written medication guide prior to contrast administration. A radiologist or designated physician should be immediately available when contrast is administered. Emergency medications and equipment should be available in the department.

Nephrogenic Systemic Fibrosis: In 2006, it was recognized that patients with renal failure who were exposed to GBCA were at increased risk of developing a potentially fatal disorder known as nephrogenic systemic fibrosis (NSF). In response, the FDA issued a “black box” warning for all GBCA with respect to assessing renal function prior to GBCA administration. This warning, coupled with a concerted international effort to limit GBCA exposure to patients at increased risk of NSF due to renal failure, has successfully eliminated the incidence of NSF cases with any agent anywhere in the world since 2008.
Further research has shown a variable propensity for the development of NSF depending upon the type of GBCA. Specifically, almost all unconfounded cases have been reported after exposure to gadodiamide (Omniscan), gadopentetate dimeglumine (Magnevist), and/or gadoversetamide (Optimark). As a result, the FDA, and American College of Radiology (ACR) Committee on Drugs and Contrast Media, and other organizations have classified GBCAs based on reported association with NSF in vulnerable patients. The ACR classification is provided here, with these guidelines mirroring those established by the ACR:

 

Further research has shown a variable propensity for the development of NSF depending upon the type of GBCA. Specifically, almost all unconfounded cases have been reported after exposure to gadodiamide (Omniscan), gadopentetate dimeglumine (Magnevist), and/or gadoversetamide (Optimark). As a result, the FDA, and American College of Radiology (ACR) Committee on Drugs and Contrast Media, and other organizations have classified GBCAs based on reported association with NSF in vulnerable patients. The ACR classification is provided here, with these guidelines mirroring those established by the ACR: 

 

 

Gadolinium tissue deposition: Recent studies have shown gadolinium deposition in the brain and other tissues including bone and skin; this may be dose dependent and can occur in patients with no clinical evidence of kidney or liver disease. The clinical relevance of Gadolinium retention, if any, currently is not known. There have been no reports to date to suggest brain deposits are associated with histologic changes that would suggest neurotoxicity. Rarely, patients have reported pains, tiredness, and skin, muscle, or bone ailments, but these symptoms have not been directly linked to gadolinium. The term, Symptoms Associated with Gadolinium Exposure (SAGE), has been suggested to describe such complaints without prematurely attributing them to a specific disease. The amount of deposited gadolinium varies between GBCA and appears to be related to the stability of the chelate, likely related to molecular structure (linear vs macrocyclic). Deposition is greater after injection of linear agents such as Omniscan or OptiMARK followed by the other linear agents Eovist, Magnevist, or MultiHance. Deposition is the least after administration of macrocyclic agents such as Clariscan, Dotarem, Gadavist, or ProHance. All patients receiving GBCA should be offered an FDA approved written medication guide, specific to the agent being used, prior to contrast administration.

 

Choice of contrast agents: Due to decreased risk of NSF, a streamlined screening process, and decreased brain deposition, Group II GBCA are strongly encouraged for routine use at our imaging centers and our partner hospitals. With unique partial biliary and renal excretion, use of Eovist, a Group III agent, is encouraged for appropriate indications, as determined by body section guidelines. The type and dosage of GBCA must be documented by the technologist on each case. Dosage is weight-based, and care should be used to always use the lowest dose possible to achieve diagnostic results. 

 

Patient selection and screening: Screening questions include: 

• Allergic reaction to GBCA, and other drugs. The premedication regimen is outlined below. Switching to a new type of GBCA may be prudent, but has not been shown to reduce the likelihood of a repeat reaction. A previous reaction to iodinated contrast media does not necessitate premedication for GBCA, as there is no cross-reactivity between the two agents. 
• Renal impairment. The routine screening for renal failure and laboratory testing of serum creatinine (Cr) is no longer required for patients when a Group II GBCA will be used. When a Group II is not used (Group I GBCA are no longer recommended, Group III GBCA are used occasionally), the following risk factors can be used to identify patients who have impaired renal function:
  • Personal history of renal disease, including:
    • Recent or remote history of acute kidney injury (AKI). AKI is an abrupt reduction in kidney function often with decreased urine output (increase of serum creatinine by >0.3 mg/dL within 48 hours OR an increase in serum creatinine by 50% within 7 days).  Among many causes are dehydration, NSAID and other nephrotoxic medications, heart failure, sepsis, hypotension, and urinary obstruction.
    • Known chronic kidney disease (CKD)
    • Kidney surgery, kidney cancer or ablation, kidney transplant, single kidney
  • Diabetes mellitus

Creatinine screening:

• For outpatients: If a patient answers “no” to all of the above questions OR a Group II agent will be administered, then there is no need to draw a serum Cr.  If a patient answers “yes” to any of these questions AND a Group I or Group III agent will be administered, then a serum Cr must be obtained with calculated eGFR (mL/min/1.73m²).  In stable outpatients, an eGFR result within the past 30 days is adequate.  Point of care (POC) testing devices may be used if they are subject to appropriate quality control monitoring and results are recorded.
• For ED and inpatients: If a Group II agent will be administered, then there is no need to draw a serum Cr.  If a Group I or Group III agent will be administered, then an eGFR result within 48 hours should be available regardless of renal risk factors.
• Patients on dialysis or with documented acute kidney injury (AKI) do not require eGFR as it is not accurate in these situations; however, the need for a GBCA should be discussed with a radiologist (see below).

 

 

GBCA administration in patients with renal dysfunction, strategies to prevent NSF:

• Confirm that contrast is necessary for the study and clinical problem
  • Patients on dialysis, or with eGFR <30, or known AKI are at increased risk of NSF. If a Group I or Group III agent is being considered in a patient at increased risk of NSF, the radiologist and referring provider should be consulted to discuss the risks and benefits, and informed consent of the patient should be obtained.  If a Group II agent is used, the radiologist should be consulted to confirm that contrast is needed, although a risk-benefit discussion between the radiologist and referring provider is not necessary, and informed consent of the patient is not required.  In some acute clinical situations, the use of GBCA may be necessary regardless of NSF risk and documentation of the rationale is recommended.  Consider non-contrast examination or alternative imaging modality.
• Unlike iodinated contrast media, GBCA are not considered nephrotoxic at dosages approved for MR imaging. Therefore, prophylaxis such as hydration is not indicated for the prevention of NSF.  Risk mitigation strategies include the use of Group II GBCA and awaiting kidney function recovery. 
• The lowest dose of GBCA required to obtain the needed clinical information should be used in at-risk patients, and it should generally not exceed the recommended single dose.
• Acute kidney injury (AKI)
  • Group I should be avoided.
  • Group II agents are strongly preferred. Confirm the need for contrast with a radiologist.
  • Group III agents are used only if critical for diagnosis, with risk/benefit per radiologist, and informed consent of the patient.
• Chronic kidney disease (CKD) stages 1-3, eGFR 30-119
  • No special precautions, any Group GBCA may be used.

• CKD stage 4 or 5, eGFR <30, not on chronic dialysis
  • Group I agents contraindicated, do not use.
  • Group II agents preferred. For inpatients, confirm the need for contrast with a radiologist.
  • Group III agents used only if critical for diagnosis, with risk/benefit per radiologist, and informed consent of the patient.
• End stage renal disease (ESRD) on chronic dialysis
  • Consider CT with contrast instead, if similar diagnostic yield
  • Group I agents contraindicated, do not use.
  • Group II agents may be used, if necessary for diagnosis (confirm with radiologist), with hemodialysis (HD) performed as closely following the injection as possible. Peritoneal dialysis may provide less risk reduction than HD, though this has not been well studied.
  • Group III agents used only if critical for diagnosis, with risk/benefit per radiologist, informed consent of the patient, and dialysis performed as soon as possible.
• Children
  • Follow same guidelines for NSF risk reduction as adults

Strategies to Prevent Allergic Contrast Reactions:

• Confirm that contrast is necessary for the study and clinical problem
  • If there is a history of prior moderate or severe allergic reaction to GBCA (see categories below), the radiologist and referring provider should be consulted to discuss the risks and benefits. Consider non-contrast examination, alternative imaging modality, or premedication.
• If the prior contrast agent is known, then switch to another agent
  • Switching to a new type of GBCA may be prudent, but there are no published studies that confirm a reduction in the likelihood of a repeat reaction.
• Premedication
  • Indicated for prior allergic reactions to GBCA of any severity
  • Not indicated for asthma and allergies to shellfish, topical iodine, or iodinated contrast media
  • Not indicated for physiologic reactions (nausea, vomiting, flushing/warmth, vasovagal reaction)
• Patients with a history of moderate and severe allergic reactions to GBCA should have their exams performed at a hospital with on-site availability of ACLS advanced airway equipment and an anesthesiologist or emergency physician

Premedication Regimens:

• Steroids: Medrol (methylprednisolone) 32mg PO 12 hours and 2 hours before procedure or Prednisone 50mg PO 13hrs, 7hrs and 1 hour before procedure.  For patients who cannot take oral steroids, 200mg hydrocortisone IV may be substituted for each dose of oral prednisone.  There is no value to giving first dose of steroids within 3 hours of procedure.
• Antihistamines: Benadryl 50mg IV or PO 1 hour prior to procedure (must be combined with steroids above). 
• Accelerated IV Premedication (only for emergent examinations): Methylprednisolone sodium succinate (e.g., Solu-Medrol®) 40 mg IV or hydrocortisone sodium succinate (e.g., Solu-Cortef®) 200 mg IV immediately, and then every 4 hours until GBCA administration, plus diphenhydramine 50 mg IV 1 hour before contrast medium administration.  Minimum pretreatment duration is 5 hours.

 

 

Contrast Allergic Reaction Categories:

Mild

Limited urticaria / pruritis

Cutaneous edema

Limited “itchy”/”scratchy” throat

Nasal congestion

Sneezing / conjunctivitis / rhinorrhea

 

Moderate

Diffuse urticaria / pruritis

Diffuse erythema, stable vital signs

Facial edema without dyspnea

Throat tightness or hoarseness without dyspnea

Wheezing / bronchospasm, mild or no hypoxia

 

Severe

Diffuse edema, or facial edema with dyspnea

Diffuse erythema with hypotension

Laryngeal edema with stridor and/or hypoxia

Wheezing / bronchospasm, significant hypoxia

Anaphylactic shock (hypotension + tachycardia)

 

 

Multiple doses of GBCA:  In patients not at risk of NSF, there are no contraindications to multiple, closely spaced, doses if the examination is determined to be necessary.  The risk of multiple closely spaced doses has not been evaluated in patients with eGFR <30, although if there is an urgent indication that requires closely spaced doses, the exam should not be delayed for fear of NSF.  If not urgent, delaying the subsequent dose(s) >24 hours or performing intercurrent dialysis can promote GBCA clearance.  Group II agents are strongly recommended, with care to use the lowest dose necessary for a diagnostic scan.

 

Breastfeeding: The expected systemic dose to the infant is less than 0.0004% of the dose to the mother. Any potential risks are theoretical, with no complications having been reported. It is considered safe to continue breastfeeding, though if a mother is concerned for any potential ill effects, breast feeding may be withheld for 12-24 hours, discarding breast milk during that time. The radiology staff should help her make an informed decision.

 

Pregnancy: There are currently no known deleterious effects of MR imaging on the fetus, and we consider MRI to be a safe imaging modality for pregnant patients. However, it is unclear how GBCA will affect the fetus, and should be only administered if usage of GBCA is considered critical, and the potential benefits justify the potential unknown risk to the fetus. If GBCA is deemed absolutely necessary, informed consent should be completed, and the following documented in the chart:

• The information requested from MRI cannot be determined without IV contrast.
• The information needed affects the care of the patient and/or fetus during pregnancy.
• The referring physician is of the opinion that it is not prudent to wait for this information until after the patient is no longer pregnant.

 

Pediatric Patients:

• Use weight-based dosing.
• Strongly consider alternative imaging methods in the rare case of children with MRI contrast allergy. Any steroid pre-treatment must be ordered by a pediatrician. Allergic patients should only be given contrast when a PALS certified pediatric anesthesiologist or emergency physician is informed, on site and available.
• Follow the same renal function precautions as adults for prevention of NSF.

 

Reference: 

ACR Manual on Contrast Media, 2021 (https://www.acr.org/Clinical-Resources/Contrast-Manual)

Weinreb JC, Rodby RA, Yee J, et al., Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Diease: Consensus Statements from the American College of Radiology and the National Kidney Foundation. Radiology 2021; 298:28-35. https://doi.org/10.1148/radiol.2020202903