INTRODUCTION — Health care providers who refer a patient for magnetic resonance imaging (MRI) must consider whether to request the examination with contrast. Intravenous administration of a gadolinium-based contrast agent (GBCA) is indicated in over one-third of MRI examinations to obtain the necessary information. While GBCA is well tolerated in most patients, it is associated with a small risk for nephrogenic systemic fibrosis (NSF) or acute adverse reaction. Long-term deposition of gadolinium in body tissues, including the brain, have also been noted following intravenous GBCA administration.
Both the referring provider and the radiologist share the clinical and legal responsibility for a patient who undergoes an imaging examination. However, most third-party payers require that contrast be specified at the time of examination ordering. Thus, the provider is asked to make the initial choice after considering both the risks and benefits of GBCA administration in each patient. If the choice is not obvious, a dialogue between the referring provider and the radiologist can be helpful.
Appropriate use of intravenous GBCA is necessary to obtain acceptable test performance with MRI. Omitting contrast when it is indicated can lead to diagnostic and treatment errors; giving it when it is not indicated can result in avoidable morbidity and cost. Added or repeated tests and delayed diagnoses are the potential adverse effects of an imaging examination performed suboptimally.
Standards for patient preparation and indications for giving GBCA vary among radiology practices. However, the guiding principles are described here. Related UpToDate content discusses:
●Pathogenesis, clinical manifestations, diagnosis, and treatment of NSF – (See "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease".)
●MRI safety evaluation in a patient with metallic or electrical implants, devices, or foreign bodies – (See "Patient evaluation for metallic or electrical implants, devices, or foreign bodies before magnetic resonance imaging".)
●Pathogenesis, diagnosis, and treatment of adverse reactions to intravenous contrast – (See "Diagnosis and treatment of an acute reaction to a radiologic contrast agent".)
TYPES OF CONTRAST MEDIA — Choice and dose of gadolinium-based contrast agents (GBCA) administered is primarily determined by the body part to be imaged and the clinical indication. While the radiology practice group, hospital, or health care system formularies determine the GBCAs available for use, many imaging sites have more than one type of GBCA on hand, as each differ in physiochemical properties, safety profiles, and imaging attributes. In general, an imaging service will administer one type of GBCA as the default, unless an alternative is clearly preferable in an individual case for reasons of patient safety or specific clinical indication.
All commercially available GBCAs are molecularly composed of gadolinium (Gd+3) bound to a chelating ligand. GBCAs are categorized as linear versus macrocyclic, based on the molecular structure of the ligand, and as nonionic versus ionic, based on whether they are charged in solution. As a rule of thumb, macrocyclic agents are more stable than linear, and ionic agents are more stable than nonionic. While free Gd+3 is highly toxic, chelation makes a GBCA safe for intravenous injection while maintaining the paramagnetic properties of the gadolinium for MRI [1,2]. Generic and brand names and the molecular properties of the commercially available GBCAs can be found in the American College of Radiology Manual on Contrast Media .
Most GBCAs are purely extracellular (gadopentetate, gadoterate, gadodiamide, gadoteridol, gadobutrol, gadoversetamide, and gadopiclenol), demonstrate no protein binding, and are excreted by glomerular filtration in urine [4,5]. Two agents (gadobenate and gadoxetate) demonstrate weak protein interactions and are taken up by the hepatocytes and excreted, in part, by the hepatobiliary system as well as the kidneys.
INDICATIONS FOR GIVING CONTRAST WITH MRI — The clinical indication of the examination determines the need for a gadolinium-based contrast agent (GBCA) (table 1).
The American College of Radiology's (ACR) Appropriateness Criteria describes consensus recommendations on the choice of imaging modality and contrast use for many clinical scenarios . UpToDate topics that recommend MRI for patient management may specify whether contrast is required, preferred, or not necessary for a given clinical situation.
Some general principles for determining when GBCA might be given are as follows:
●Central nervous system – A GBCA is administered for most brain MRI examinations and for most spine MRI examinations performed for indications other than back pain. Disruption of the blood brain barrier by a lesion (eg, neoplasm, infection, or active inflammation) is readily detected with GBCA and facilitates differentiation of edema from other pathology .
●Breast – A GBCA is routinely administered in breast MRI for cancer detection, treatment planning, and for follow-up after treatment [8,9]. Clinical indications for gadolinium contrast administration in MRI. (See "MRI of the breast and emerging technologies".)
●Cardiac – A GBCA is administered in cardiac MRI to evaluate for ischemic and nonischemic cardiomyopathies, to assess myocardial perfusion, and to characterize tumor . (See "Clinical utility of cardiovascular magnetic resonance imaging" and "Cardiac tumors", section on 'Cardiac magnetic resonance imaging and computed tomography'.)
●Musculoskeletal – The majority of MRI examinations of the musculoskeletal system (ie, joints, bones, and soft tissue of the upper and lower extremities) are performed without a GBCA administration. A GBCA is administered for MRI of suspected or known osteomyelitis or soft tissue neoplasm. Dilute intra-articular GBCA is sometimes injected into a joint capsule for arthrography . (See "Imaging techniques for evaluation of the painful joint", section on 'MR arthrography'.)
●Abdomen and pelvis – Abdominal and/or pelvic MRI performed to evaluate the liver, kidneys, pancreas, bowel, and pelvic organs (eg, bladder, uterus, ovaries, prostate) often involve GBCA administration.
●Blood vessels – GBCA may be administered for magnetic resonance angiography (MRA), as contrast administration significantly improves image quality when compared with noncontrast MRA [11,12].
Each individual GBCA is approved by the United States Food and Drug Administration (FDA) for specific MRI indications. Thus, some of the indications for which GBCA is commonly used may be considered "off-label" uses for some of the commercially available agents.
APPROACH TO PREVENTING NEPHROGENIC SYSTEMIC FIBROSIS — Nephrogenic systemic fibrosis (NSF), while rare, has been strongly associated with gadolinium administration in patients with severely impaired kidney function [13-15].
NSF manifests as progressive fibrosis, primarily of the skin and subcutaneous tissues. However, other organs such as the lungs, esophagus, heart, and skeletal muscles can also be involved. Diagnosis is made on histopathology of a biopsy specimen from a clinically involved site. The disease can develop and progress rapidly, and is sometimes fatal. The likelihood of developing NSF depends on the molecular type of gadolinium-based contrast agent (GBCA), and some agents have been associated with no or very few unconfounded cases. Screening of kidney function in patients receiving a GBCA and increased use of these GBCAs have contributed to the decreased cases of NSF since 2007 . (See "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease".)
Thermodynamic stability of the chelating ligand is thought to be an important variable that determines why certain GBCAs are associated with higher incidence of NSF. The favored hypothesis is that delayed excretion due to severe renal compromise promotes the release of free gadolinium (Gd+3) within the body, thereby serving as the initial step in the pathogenesis of the disease [16,17].
Gadolinium group and risk for nephrogenic systemic fibrosis — While GBCA classification schemes slightly differ based on the regulatory agency describing it, they all categorize GBCAs based upon their associated risk of NSF [3,18,19]. The American College of Radiology (ACR) describes three GBCA groups: I, II, and III . Reported NSF cases are categorized as confounded or unconfounded. Unconfounded cases are those where the implicated gadolinium agent was the only type that the patient received before the diagnosis of NSF.
●Group I – Associated with the largest number of NSF cases (gadodiamide, gadopentetate, gadoversetamide). These agents all contain linear ligands and nearly all reported cases of NSF have been associated with them. Gadodiamide, gadopentetate, and gadoversetamide are associated with 70, 20, and 4.8 percent of NSF cases, respectively . These GBCAs are no longer marketed in the United States or Europe.
●Group II – Associated with few or no verified unconfounded NSF cases (gadobenate, gadobutrol, gadoteridol, gadoterate meglumine). However, there have been many cases of NSF reported with group I agents that are confounded by use of a group II agent. Most group II agents contain macrocyclic ligands except for gadobenate, which contains a linear ligand.
•In a 2019 review, group II exposures were reported in 23 of 405 patients diagnosed with NSF . Of these, only two were unconfounded [21,22], while two additional patients with NSF were given a group II GBCA with another unknown GBCA, precluding an assessment of confounding .
•In a systematic review and meta-analysis composed of 4931 patients, no patient with stage 4 or 5 chronic kidney disease (CKD; estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2) developed NSF after group II GBCA administration .
●Group III – Limited data due to insufficient number of administrations. The group III GBCA gadoxetate disodium, which is primarily used for the detection and characterization of focal liver lesions, has not been associated with an unconfounded case of NSF .
The health care provider should be familiar with the GBCA group routinely administered by the imaging service and their institutional policies as these will, in certain patients, determine whether an eGFR needs to be calculated before the examination or whether a different imaging strategy that avoids GBCA needs to be pursued. The MRI may be delayed if eGFR requires measurement when the patient presents for imaging or if the result requires that the imaging procedure be modified or rescheduled.
Evaluation to identify those patients who may be at risk for NSF differ based upon which agents are to be given [3,26]. As an example, an eGFR may need to be checked in those at risk for kidney function impairment if a group I or III agent is to be given, but not if a group II agent is to be administered (see 'Which patients need an assessment of eGFR?' below). Additionally, in patients on dialysis or with acute kidney injury (AKI), a discussion with a radiologist on alternative imaging strategies is necessary before referring them for MRI. In these patients, group I agents are contraindicated, whereas group II agents can be given if no other diagnostic options are available (algorithm 1). (See 'Patients on dialysis' below and 'Patients with eGFR <30 mL/min/1.73 m2 or with acute kidney injury' below.)
Patient risk factors for nephrogenic systemic fibrosis — Patients with the following conditions are at risk for nephrogenic systemic fibrosis (NSF) (algorithm 1):
●End-stage kidney disease on dialysis of any type.
●Acute kidney injury (AKI) (table 2). Diagnostic criteria for AKI are described elsewhere in UpToDate. (See "Definition and staging criteria of acute kidney injury in adults".)
●CKD with eGFR<30 mL/min per 1.73 m2.
The degree of renal impairment, rather than the duration or etiology of kidney disease, is the primary factor determining the risk of NSF. Most cases have been reported in patients with end-stage kidney disease on dialysis [14,15]. In patients with stage 4 or 5 CKD, the risk of developing NSF after one or more exposures to certain GBCAs is estimated at 1 to 7 percent. A review of 519 patients with NSF noted that 80.9 percent were dialysis-dependent, 7.8 percent had stage 4 and 5 CKD, and 11.3 percent had AKI [27,28]. Only one case of NSF in a patient with stage 3 CKD (eGFR 30 to 59 mL/min per 1.73 m2) has been reported and none in patients with eGFR above 60 mL/min per 1.73 m2 .
AKI, with or without underlying CKD, is also a risk factor for NSF. In a series of 83,121 patients from two centers, the incidence of NSF following gadodiamide exposure was 19 percent in patients with AKI or those with rising creatinine levels who were not dialyzed within 48 hours of the GBCA exposure .
A patient with renal impairment should be considered at risk for NSF even if GBCA has never been previously administered. NSF cases after a single exposure to a standard dose (ie, 0.1 mmol/kg) of GBCA have been reported [31,32]. However, most cases of NSF have been associated with patients who received multiple doses of GBCA and often at larger than standard doses.
The risk of developing NSF has also been associated with higher doses of GBCAs, either as a single dose or cumulatively over multiple administrations [33,34]. In one series, 90 percent (163/182) of patients with NSF had received greater than the standard dose . The incidence of NSF was higher in patients exposed to larger doses of GBCA compared with standard dose for magnetic resonance angiogram (MRA) .
A history of a prior kidney transplant is not considered an independent risk factor for developing NSF .
Patients with hepatorenal syndrome or those in the perioperative liver transplantation period were once thought to be at an increased risk for NSF . However, multiple studies have refuted this association [38,39]. Thus, these variables are no longer considered independent risk factors for NSF.
Other proposed risk factors include exposure to lanthanum carbonate, high-dose erythropoietin treatment, metabolic acidosis, proinflammatory conditions, and elevated iron or phosphate levels . However, none of these has demonstrated a definitive association or a causal relationship, and we do not advise screening for them.
Which patients need an assessment of eGFR? — Clinical history and, in some patients, an eGFR are used to screen for impaired kidney function (calculator 1). Criteria for requiring an eGFR measurement vary with each practice. Ours is described here (algorithm 1). (See "Assessment of kidney function".)
If a group II GBCA is to be given, an eGFR does not need to be obtained. If group I or III GBCA is to be given, eGFR is obtained in patients with risk factors for renal impairment. These include:
●Kidney disease (eg, history of dialysis or renal cancer, kidney transplant or surgery, single kidney)
●Hypertension requiring medical treatment
The eGFR is not useful in assessing kidney function status prior to giving GBCA in patients:
●With AKI (table 2). Diagnostic criteria for AKI are described elsewhere in UpToDate. (See "Definition and staging criteria of acute kidney injury in adults".)
How recent does the eGFR assessment need to be? — Medical judgement should be used to determine if an eGFR is likely to reflect that patient's kidney function. eGFR may be misleading in patients with rapidly changing kidney function or in patients with extremes in body type. However, in general, in most patients an eGFR determined within the prior 30 days in an outpatient setting and within 48 hours in an inpatient setting is likely to suffice.
Patients with known or presumed normal eGFR
●Patients not on dialysis, without AKI, and with no risk factors for renal impairment – MRI can be safely performed using a group I, II, or III GBCA. (See 'Which patients need an assessment of eGFR?' above.)
●Patients with an eGFR measuring ≥60 mL/min per 1.73 m2 – Gadolinium-enhanced MRI can be safely performed using any group I, II, or III GBCA. There have been no proven cases of NSF in patients with an eGFR ≥60 mL/min per 1.73 m2.
Patients with eGFR 30 to 59 mL/min/1.73 m2 — Gadolinium-enhanced MRI can be performed. Many practices consider any type of GBCA to be safe. Some practices avoid using group I GBCA.
The ACR suggests that all GBCA agents can be given to patients with an eGFR between 30 to 59 mL/min per 1.73 m2 without special precautions  (although group I GBCAs are no longer marketed in the United States). In addition, all group I agents and one group II agent (gadobenate dimeglumine for nonhepatobiliary imaging) have been withdrawn from clinical use in Europe primarily related to concerns for gadolinium retention; the European Society of Urogenital Radiology (ESUR) restricts options to only the remaining GBCAs .
An unconfounded case of NSF associated with a group I GBCA has been reported in a patient with an eGFR between 30 to 59 mL/min per 1.73 m2 . Additional cases have been reported to the Food and Drug Administration (FDA), but these cases are considered unconfirmed as they do not document kidney function at the time of GBCA administration nor the method by which NSF was diagnosed .
Patients with eGFR <30 mL/min/1.73 m2 or with acute kidney injury — Avoid gadolinium contrast administration, if possible. Consider alternative diagnostic strategies including noncontrast MRI and other imaging modalities. A discussion with the radiologist will likely be helpful in decision making.
If a gadolinium-enhanced MRI is considered a medical necessity, group II agents should be used preferentially. Group I agents are contraindicated [3,18,40].
Both the ACR and ESUR suggest that the lowest possible dose of GBCA be used to address the diagnostic question [3,40]. If multiple doses are required to be given over a short time frame, the ACR recommends using a group II agent while the ESUR advises to refrain from giving a repeat GBCA dose in the following seven days. Whether dialysis is protective of NSF is uncertain. Advice on whether or not dialysis should be initiated, or whether the risks of dialysis may outweigh the possible benefits, is not consistent amongst recommendations from various organizations [3,40]. Approach toward dialysis in this setting is discussed elsewhere. (See "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease", section on 'Prevention'.)
Patients on dialysis — Avoid gadolinium contrast administration, if possible. Consider alternative diagnostic strategies including noncontrast MRI and other imaging modalities. If the patient is anuric and there is no anticipation of recovery of kidney function, an iodinated contrast-enhanced computed tomography (CT) is safe and can sometimes be substituted, depending on the clinical indication for imaging. A discussion with the radiologist will likely be helpful in decision making.
If a gadolinium-enhanced MRI is considered a medical necessity, a group II agent should be used. Group I agents are contraindicated [3,18,40]. Both the ACR and ESUR advise that the lowest possible dose of GBCA be used to address the diagnostic question and the ESUR further recommends that no additional doses of GBCA be given for seven days [3,40].
In patients on chronic hemodialysis, both the ACR and FDA recommend timing the GBCA-enhanced MRI as close as possible to the next hemodialysis session, in order to help clear the agent [3,41]. The protective role of hemodialysis on NSF, however, is unproven.
PATIENT WITH HISTORY OF REACTION TO GADOLINIUM CONTRAST
Acute reaction — Acute adverse reactions to gadolinium-based contrast agents (GBCAs) are defined as those that occur within one hour of contrast administration . If contrast-enhanced MRI is clinically indicated in these patients, the signs and symptoms associated with the index reaction and the molecular GBCA type that was given are all relevant to deciding whether contrast can be safely readministered (algorithm 2).
In any patient with a history of an acute reaction to contrast, the health care provider should verify that the reaction was to a GBCA given for MRI rather than to an iodinated contrast agent used for computed tomography (CT), radiography, fluoroscopy, or angiography. A prior reaction to an enterally administered (ie, oral or rectal) contrast is not usually relevant as these are rarely gadolinium-based. The details of the index reaction, such as symptoms, their duration, and any required therapy should also be elicited. If possible, the chemical or trade name of the contrast that elicited the index reaction should also be ascertained.
A history of an adverse reaction to a GBCA increases the risk of developing a subsequent reaction to GBCA. Recurrence rate of an immediate allergic-like reaction to GBCA is approximately 30 percent, which is nearly 200-fold above the baseline rate . A prior adverse reaction to gadopentetate dimeglumine is associated with an eightfold increase in developing a subsequent reaction .
A history of an uneventful prior GBCA administration does not guarantee lack of future risk. In one series, 28 of 82 patients (ie, 34 percent) who had an allergic-like reaction to gadobutrol had previously received a GBCA without a reaction .
Determine the clinical features of the index reaction — The index contrast reaction is classified based on symptom severity (mild, moderate, or severe) and underlying physiology (allergic-like or physiologic). This classification predicts the likelihood and probable severity of a recurrent reaction. Based on this assessment, decisions are made on whether GBCA can be safely readministered and, if so, the precautionary measures needed before readministration (algorithm 2).
Allergic-like reactions are idiosyncratic as they are not related to dose, may occur in patients without prior exposure, and do not predictably recur after each antigen exposure. Symptoms and signs of allergic-like reactions are:
●Urticaria or pruritus
●Sneezing, conjunctivitis or rhinorrhea, or facial edema
●Hoarseness or stridor, with or without hypoxia (ie, upper airway compromise)
●Bronchospasm or wheezing, with or without hypoxia (ie, lower airway compromise)
●Anaphylactoid shock (ie, hypotension and tachycardia)
Physiologic reactions are dose-dependent and are thought to vary with the individual chemical properties of the contrast agent. Symptoms and signs of physiologic reactions are:
●Transient warmth or chills
●Nausea or vomiting
●Vasovagal reaction (ie, hypotension and bradycardia)
Reactions with both allergic-like and physiologic features should be classified as allergic-like. Cardiopulmonary arrest is a nonspecific result of either a severe allergic-like or physiologic reaction. An allergic-like reaction should be assumed if the categorization is unclear.
Hypersensitivity reactions to GBCA are considered allergic-like because an antigen-antibody response often cannot be identified. True allergic reactions to GBCA, as confirmed by skin testing, are rare but have been reported . (See "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease".)
Mild, moderate, and severe reactions — An acute reaction to GBCA is classified as mild, moderate, or severe based on the nature of the symptoms, their duration, and the requirement for therapy (algorithm 2).
Reactions are classified by severity as follows:
●Mild – Reaction is self-limited, does not progress, and rarely requires treatment
●Moderate – Reaction usually requires treatment and may progress to a severe reaction if untreated
●Severe – Reaction is life-threatening and can cause significant morbidity
Severity of the index reaction is a factor in deciding whether GBCA can be safely readministered. In patients with a history of a severe reaction, we avoid gadolinium administration. In patients with a history of a mild or moderate reaction, contrast-enhanced MRI can be performed if alternative diagnostic tests (eg, MRI without contrast, CT, observation) are not a viable option [3,26]. However, precautionary measures prior to contrast readministration are necessary. (See 'Measures to prevent or anticipate a recurrent reaction' below.)
The majority of reactions are mild. The overall likelihood of a moderate or severe allergic-like reaction to GBCA is <1 in 1,000 administrations. Approximately 0.08 to 0.67 percent of GBCA administrations elicit an acute allergic-like reaction [42,45-52]. Among allergic-like reactions, mild, moderate, and severe reactions comprise 81, 13, and 6 percent of all adverse events . For physiologic reactions, a study of 28,078 gadoteridol administrations reported mild (eg, nausea, vomiting) and severe (eg, chest pain, seizure) reactions that corresponded to 25 percent and <0.01 percent, respectively, of the 187 observed acute reactions .
Contrast agent associated with the index reaction — The referring provider should try to identify the specific name of the GBCA that caused the reaction and communicate this to the radiologist. The medical record from the index reaction, including the imaging report itself, will likely document this information. Commercially available contrast agents and their molecular and trade names are found in the American College of Radiology Manual on Contrast Media. If contrast-enhanced MRI is deemed necessary, some imaging practices will give a different GBCA, if available. However, there is no evidence that substitution of a different molecular type of GBCA decreases the likelihood of an acute reaction.
The rates of acute allergic-like reaction associated with GBCAs vary with the physiochemical properties of the ligand . In a single-center retrospective study of 281,945 GBCA injections in 158,100 patients and a systematic review and meta-analysis of nine studies with a total of 716,698 GBCA administrations, higher acute reaction rates were associated with agents that are ionic, are protein-binding, and have a macrocyclic structure [53-55]. However, the rates are small for all of the agents. In one study of 6163 patients, for example, there were 15 immediate-type adverse reactions in 10 patients (0.16 percent) .
Measures to prevent or anticipate a recurrent reaction — The health care provider should consult the radiology service when referring a patient with a history of an acute reaction for contrast-enhanced MRI. The discussion should be aimed at deciding whether imaging can be modified to avoid contrast and, if GBCA administration is deemed necessary, whether premedication prophylaxis should be administered. These choices are unique to each scenario as the risks of a potential recurrent reaction need to be weighed against the potential benefits of obtaining the diagnostic information from the imaging examination.
If contrast administration is planned, preparations should be made to perform the examination in a setting where medical expertise is available to treat a reaction.
Some practices administer a corticosteroid with or without antihistamine in patients with a history of an allergic-like reaction. This premedication regimen is analogous to the one used for iodinated contrast (table 3). However, there is no evidence to indicate that this prophylaxis decreases the risk of a recurrent reaction to GBCA. As an example, in one systematic review, recurrent hypersensitivity reactions occurred despite administration of corticosteroids in more than one-third of patients . (See "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography", section on 'Preventing recurrent allergic-like reactions'.)
The choice to readminister GBCA in a patient with a history of an acute reaction is individualized based on the features of the index reaction, MRI examination indication, alternatives for diagnostic testing, and patient preferences. Our approach to the decision-making is as follows (algorithm 2):
●Severe allergic-like or physiologic – Do not administer a GBCA. Other tests should be pursued, including noncontrast MRI, CT, or ultrasound if they are likely to prove diagnostic. Alternatively, consider foregoing the diagnostic workup and treating presumptively.
●Moderate or mild allergic-like – Avoid administering a GBCA if clinically possible. Other tests should be pursued, including noncontrast MRI, CT, or ultrasound, if they are likely to prove diagnostic. If contrast-enhanced MRI is deemed necessary, the examination should be performed in a setting where expertise to treat a recurrent reaction is readily available. We give premedication if the time to examination and patient's comorbidities allow. If the chemical or trade name of the GBCA causing the index reaction is known, a different one, if available, should be given.
●Moderate or mild physiologic – Avoid administering a GBCA if clinically possible. Other tests should be pursued, including noncontrast MRI, CT, or ultrasound, if they are likely to prove diagnostic. If contrast-enhanced MRI is deemed necessary, the examination should be performed in a setting where expertise to treat a recurrent reaction is readily available. If the chemical or trade name of the GBCA causing the index reaction is known, a different one, if available, should be given.
Delayed reaction — Delayed hypersensitivity reactions (ie, occurs ≥1 hour following GBCA exposure) have been reported and all have been mild . They have been described to occur up to a day following exposure to contrast. The most common symptom of a delayed reaction was urticaria. Severe physiologic symptoms such as arrhythmia and hypertonia have been reported days after GBCA administration, although in such cases, whether the symptoms represent a contrast reaction is less clear . As we have no data on whether premedication is protective in this setting, we do not premedicate when readministering GBCA to these patients.
PATIENT WITH HYPERSENSITIVITY TO OTHER AGENTS OR WITH ASTHMA — In patients with hypersensitivity to other allergens unrelated to gadolinium-based contrast agents (GBCAs) and in patients with asthma, approach toward premedication varies among different practices. European Society of Urogenital Radiology (ESUR) advises considering premedication in these patients whereas American College of Radiology (ACR) suggests that this is unnecessary [3,40].
In our practice, we do not premedicate patients with asthma or hypersensitivity to other agents before giving GBCA. There is no evidence that indicates that premedication decreases the risk of an acute reaction to GBCA.
The risk of an acute reaction to GBCA is approximately two to four times higher in patients with asthma or hypersensitivity to other agents [43,59]. However, the overall risk for a moderate or severe reaction in this population is still <1 in 1000.
No cross reactivity between GBCA and iodinated contrast used in computed tomography (CT), radiography, fluoroscopy, or angiography, has been identified.
Children — With the pediatric population, the approach to gadolinium administration and the associated risks of nephrogenic systemic fibrosis (NSF) and acute adverse events are analogous to that in adults. However, different equations are used in children to calculate estimated glomerular filtration rate (eGFR). (See 'Approach to preventing nephrogenic systemic fibrosis' above and 'Patient with history of reaction to gadolinium contrast' above and "Chronic kidney disease in children: Definition, epidemiology, etiology, and course", section on 'Estimated glomerular filtration rate'.)
Given the lack of evidence, we use adult guidelines to identify pediatric patients who are at risk for NSF. In addition, neonates and infants with renal immaturity whose eGFR could be less than 30 mL/min per 1.73 m2 represent another population potentially at risk for NSF. The American College of Radiology (ACR) suggests using group II agents in this subset of patients if clinically feasible .
NSF has been described after gadolinium-based contrast agent (GBCA) administration in children with significant kidney function impairment . One review reported that among sixteen cases of NSF associated with GBCA administration in children, 10 patients were on dialysis, two had acute kidney injury (AKI), and six had chronic kidney disease (CKD).
Adverse events associated with GBCA administration and precautionary measures for readministration are similar to that in adults. Allergic-like reactions are reported at rates of <0.05 percent [60,61].
GBCA does not cause significant fluid shifts either in the pediatric or adult population in the doses administered for MRI.
Pregnant women — Gadolinium administration to pregnant patients should be avoided as it may be associated with an increased risk of adverse fetal outcome. In pregnant women, we administer GBCA only if no other testing options are available and if diagnostic evaluation cannot be deferred until after delivery. (See "Diagnostic imaging in pregnant and lactating patients", section on 'Use of gadolinium'.)
Exposure to GBCA in utero is associated with increased rates of neonatal death (relative risk [RR] 2.6, 95% CI 1.3-5.4) and rheumatologic or inflammatory skin condition up to age four (RR 1.3, 95% CI 1.1-1.6) . An increased risk for NSF or congenital anomaly has not been observed.
Women who are breastfeeding — Approach to cessation of breastfeeding after gadolinium administration vary and are described elsewhere. (See "Diagnostic imaging in pregnant and lactating patients".)
CONCERNS ABOUT GADOLINIUM RETENTION MULTIPLE ORGANS — When a gadolinium-based contrast agent (GBCA) is administered, a small proportion of the unchelated gadolinium remains in the body, including the brain, for an indeterminate period of time. The health effects of neuronal gadolinium retention are unknown.
Several studies have reported gadolinium in the brain, bone, and liver of patients who have received GBCA [63-69]. Some patients have ascribed adverse health effects to gadolinium retention . While the presence of gadolinium in the skin in association with nephrogenic systemic fibrosis (NSF) in patients with severe kidney disease has been documented, to date there has been no scientific evidence that gadolinium retention in the brain or elsewhere is harmful.
The amount of gadolinium retention in the brain with each contrast dose appears to be associated with the molecular structure of the ligand [71-74]. Less retention is seen in the brain with macrocyclic class of agents than with the linear. Risk of retention has not been associated with patient-specific factors. Most patients with known gadolinium deposition have normal kidney function.
Regulatory agencies have taken different approaches toward the observation that gadolinium deposits in the central nervous system. The United States Food and Drug Administration (FDA) has published a class warning for all GBCAs and requires that patients be provided with educational information before receiving a GBCA . The FDA also encourages health care professionals to critically assess the need for repeated gadolinium-enhanced MRIs. However, the FDA has not withdrawn a GBCA because of the concern of deposition. In contrast, the European Medicines Agency (EMA) has withdrawn most GBCAs in the linear ligand class or significantly restricted their use . Both agencies note that evidence of health effects of neuronal gadolinium deposition is lacking.
SUMMARY AND RECOMMENDATIONS
●Appropriate use of an intravenous gadolinium-based contrast agent (GBCA) is necessary to obtain acceptable test performance with magnetic resonance imaging (MRI). Omitting contrast when it is indicated can lead to diagnostic and treatment errors; giving it when it is not indicated can result in avoidable morbidity and cost. Added or repeated tests and delayed diagnoses are the potential adverse effects of an imaging examination performed suboptimally. (See 'Introduction' above.)
●While GBCA classification schemes slightly differ based on the regulatory agency describing it, they all categorize GBCAs based on their associated risk of nephrogenic systemic fibrosis (NSF). The American College of Radiology (ACR) describes three GBCA groups: I, II, and III (table 4). The health care provider should ideally be familiar with the GBCA group routinely administered by the imaging service as this can, in certain patients, determine whether an estimated glomerular filtration rate (eGFR) needs to be measured before the examination or whether a different imaging strategy that avoids GBCA needs to be pursued. (See 'Gadolinium group and risk for nephrogenic systemic fibrosis' above.)
●Clinical history and, in some patients, eGFRs are used to screen for impaired kidney function (calculator 1). If a group II GBCA is to be given, an eGFR does not need to be obtained. If group I or III GBCA is to be given, eGFR is obtained in patients with risk factors for kidney function impairment (algorithm 1). However, group I agents are no longer marketed in the United States or Europe. (See 'Patient risk factors for nephrogenic systemic fibrosis' above.)
●Our approach to giving GBCA to prevent NSF is as follows:
•In patients with an unknown current eGFR and no risk factors for renal impairment and in patients with an eGFR ≥60 mL/min per 1.73 m2, group I, II, or III GBCA can be given safely without concern for NSF. (See 'Patients with known or presumed normal eGFR' above.)
•In patients with an eGFR measuring between 30 to 59 mL/min per 1.73 m2, group I, II, or III GBCA can be given safely without concern for NSF. However, if possible, group II or III GBCA should be given preferentially. (See 'Patients with eGFR 30 to 59 mL/min/1.73 m2' above.)
•In patients with an eGFR <30 mL/min per 1.73 m2, acute kidney injury (AKI), or on dialysis, GBCA administration should be avoided, if possible. Alternative imaging strategies should be discussed with a radiologist. If GBCA administration cannot be avoided, group II agents should be given preferentially and group I agents are contraindicated. (See 'Patients with eGFR <30 mL/min/1.73 m2 or with acute kidney injury' above and 'Patients on dialysis' above.)
●Acute adverse reactions to GBCAs are defined as those that occur within one hour of contrast administration. In any patient with a history of an acute reaction, the health care provider should verify that the reaction was to GBCA given for MRI rather than to an iodinated contrast agent used for computed tomography (CT), radiography, fluoroscopy, or angiography. The details of the index reaction such as symptoms, their duration, and any required therapy should also be elicited. (See 'Patient with history of reaction to gadolinium contrast' above.)
●The health care provider should consult the radiology service when referring a patient with a history of acute reaction to GBCA for contrast-enhanced MRI. The discussion should be aimed at deciding whether imaging can be modified to avoid contrast and, if GBCA administration is deemed necessary, whether premedication prophylaxis should be administered (algorithm 2). (See 'Measures to prevent or anticipate a recurrent reaction' above.)
●When a GBCA is administered, a small proportion of the unchelated gadolinium remains in the body, including the brain, for an indeterminate period of time. The health effects of neuronal gadolinium retention are unknown. (See 'Concerns about gadolinium retention multiple organs' above.)
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