Administration of Gadolinium Contrast in Adults Procedural Guideline

Transcription

1 Administration of Gadolinium Contrast in Adults Procedural Guideline This procedural guideline is designed to assist Radiologists by providing an analytical framework for the evaluation of gadolinium contrast dosage based on a patient s egfr. This is not intended to replace radiologist judgment nor to establish a procedure for all patients. Exceptions may be made to the guideline at the discretion of the interpreting radiologist. Procedural Statements: Gadolinium Reactions 1. Gadolinium based contrast agents are extremely well tolerated. Acute adverse reactions to gadolinium are encountered with a much lower frequency than is observed after the administration of iodinated contrast media. 2. The general dose of gadolinium is an intravenous injection of between 0.1 and 0.2 mmol/kg. a. The frequency of all acute adverse events after an injection of 0.1 or 0.2 mmol/kg of gadolinium ranges from 0.07% to 2.4%. b. Mild Reactions: The vast majority of reactions to gadolinium are mild. These most commonly include discomfort at the injection site, nausea, vomiting, headache, paresthesias, dizziness, and itching. c. Allergic Reactions: Allergic type reactions range in frequency from 0.004% to 0.7%. A rash, hives, or urticaria are the most frequent reactions seen in this group. Bronchospasm is very rare. d. Severe Reactions: Severe, life-threatening anaphylactoid or non-allergic anaphylactic reactions are exceptionally rare (0.001% to 0.01%). In two large accumulated series of 687,000 and 20,000,000 administered doses, there were 5 and 55 severe reactions, respectively. e. Fatal reactions to gadolinium chelate agents occur but are extremely rare. 3. Acute adverse reactions to gadolinium contrast media are more common in patients who have had a previous reaction to gadolinium. Subsequent reactions can be more severe than initial reactions. Patients with asthma and other allergies (the so-called atopic personality), including allergies to medications or foods are exhibit an increased risk of reaction to gadolinium. Patients who have had a previous reaction to iodinated contrast media are also at higher risk for adverse reactions. Alternative Usage of Gadolinium 4. In the past, higher doses of gadolinium were administered during CT or angiographic procedures in patients with renal insufficiency or failure. This was performed to avoid nephrotoxic iodinated contrast agents and make use of the x-ray attenuating properties of gadolinium. However, no studies have been

2 performed which establish this as a safe practice. Therefore, using gadolinium for intravascular enhancement outside of MRI should be avoided. Nephrogenic Systemic Fibrosis 5. Nephrogenic systemic fibrosis (NSF) is a fibrosing disease involving preferentially the skin and subcutaneous tissues. NSF also affects other organ systems, including the lungs, esophagus, heart, and skeletal muscles. Initial symptoms typically include skin thickening and/or itching. Symptoms and signs may develop and progress rapidly, with some affected patients developing contractures and joint immobility. In most patients, the disease is ultimately fatal. 6. It is now widely accepted that gadolinium exposure is a necessary factor in the development of NSF. The time between gadolinium administration and the onset of NSF symptoms usually occurs within days to months in the vast majority of patients. However, in some patients NSF has occurred years after the administration of gadolinium. There have also been some cases of NSF without documentation of prior gadolinium exposure. 7. The specific pathophysiology of NSF causation is unknown. The most commonly proposed hypothesis is that gadolinium ions dissociate from their parent chelates and diffuse into soft tissues to react with other ions. This results in an insoluble precipitate which remains in the soft tissues, inciting a fibrotic reaction. Patients with diminished renal function have prolonged gadolinium clearance times and thus have and thus are hypothesized to have an increased incidence of gadolinium dissociation. Other metabolic factors associated with renal disease may make association of free gadolinium ions with other ions more likely. 8. There is wide variation in the number of confirmed cases of NSF associated with the many different gadolinium contrast agents. Some gadolinium agents have been associated with few or no confirmed cases of NSF. Most cases have been reported after exposure to gadodiamide (Omniscan), gadopentetate dimeglumine (Magnevist), or gadoversetamide (OptiMark). The relationship between NSF and the different gadolinium agents is controversial, complex, and continues to evolve. Currently, the ACR has developed a classification of the various gadolinium agents based on the number of cases of NSF attributed to them.

3 Group I: Agents associated with the highest number of NSF cases Gadodiamide (Omniscan GE Healthcare) Gadopentetate dimeglumine (Magnevist Bayer HealthCare Pharmaceuticals) Gadoversetamide (OptiMARK Covidien) Group II: Agents associated with few, if any, unconfounded cases of NSF Gadobenate dimeglumine (MultiHance Bracco Diagnostics) Gadoteridol (ProHance Bracco Diagnostics) Gadobutrol (Gadavist Bayer HealthCare Pharmaceuticals) Group III: Agents which have only recently appeared in the U.S. Gadofosveset (Ablavar Lantheus Medical Imaging) Gadoxetic acid (Eovist Bayer HealthCare Pharmaceuticals) 9. At our practice sites, we currently use both group II and III agents: a. OAI/Navigator s Landing: Gadavist, Eovist b. PMMC: Gadavist c. RRMC: MultiHance, Eovist, Ablavar d. Southern Oregon Orthopedics: MultiHance e. Siskiyou Imaging: MultiHance f. Southern Oregon Open MRI: Gadavist Group I agents are not used at any of our practice sites. 10. Risk Factors for NSF: a. End Stage or Severe Chronic Kidney Disease (CKD) - CKD is the most important risk factor for the development of NSF. Most patients who have developed NSF either had end-stage kidney disease or were on hemodialysis at the time of gadolinium exposure. It is estimated that patients with end-stage CKD (egfr <15 ml/min) and severe CKD (egfr 15 to 29 ml/min) have a 1% to 7% chance of developing NSF after exposure to gadolinium. It is important to note that most severe CKD patients who have developed NSF had a lower egfr (i.e. closer to 15 than to 30). There has been only one published case report of a patient with egfr values above 30 ml/min. A second case report has been discussed but not published. i. While the development of NSF after Gadolinium administration to patients with an egfr >30 ml is exceedingly rare, egfr may fluctuate from one day to the next. An egfr level just above 30 on one day may fall below 30 on another day). Therefore, patients with

4 moderate CKD and an egfr of between are considered to be at risk for the development of NSF. ii. Moderate renal impairment (egfr of 40-60) is NOT considered a risk factor for NSF. b. Acute Kidney Injury (AKI) - AKI has been associated with between 12 and 20% of NSF cases. Many of these cases, but not all, have had underlying CKD. Therefore, AKI alone is considered to be a risk factor for NSF development. c. High dose Gadolinium exposure/multiple exposures - NSF may occur most commonly in patients who have received high doses of gadolinium, either as a single dose or cumulatively in multiple administrations over several months or even years. However, cases of NSF have also been reported in patients with a single dose of gadolinium, including a standard dose (0.1mmol/kg). i. Most patients with severe CKD who have received high and/or multiple doses of gadolinium have not developed NSF. One study described 30 patients with severe CKD who were exposed to high doses of gadodiamide (Omniscan)l. Only one of the 30 patients subsequently developed NSF. The ACR Committee on Drugs and Contrast Media considers the following patients to be at risk of developing NSF after receiving any dose of Gadolinium: Patients currently on dialysis (of any form) Patients with severe or end-stage CKD (CKD 4 or 5, egfr <30 ml/min) without dialysis Patients with moderate CKD with an egfr of between 30 to 40 ml/min without dialysis Patients with acute kidney injury (AKI) Screening for NSF Risk Prior to Gadolinium Administration 11.All patients should be screened for their risk of NSF prior to receiving any Gadolinium contrast. Screening for inpatients and outpatients differs. a. Inpatients: For all inpatients, a serum creatinine level should be obtained within two days prior to any Gadolinium contrast administration. An egfr should be calculated using the MDRD equation. This equation can be accessed on the National Kidney Foundation website:

5 Our laboratories are all traceable to IDMS. In addition, the referring clinician should assess inpatients for the possibility of AKI, as egfr calculation alone has limited sensitivity for the detection of AKI. b. Outpatients: All outpatients should be screened for conditions and other factors that may be associated with renal impairment. These factors are listed below: i. Age >60 ii. History of renal disease, including: 1. Dialysis 2. Kidney transplant 3. Solitary kidney 4. Previous kidney surgery 5. History of known cancer involving the kidney(s) iii. History of hypertension requiring medical therapy iv. History of diabetes mellitus c. Outpatients with any of the above risk factors are considered at risk for renal impairment and must have a serum creatinine drawn and an egfr calculated using the MDRD equation as detailed above prior to receiving gadolinium contrast.

6 The ACR Committee on Drugs and Contrast Media recommends a new serum creatinine be drawn and an egfr be calculated within the time intervals listed in the Chart below in outpatients who are identified by screening as at increased risk: Prior egfr Last serum creatinine drawn When should new creatinine be drawn? None Available Not Applicable Within 6 weeks > 60 ml/min Greater than 6 months ago Within 6 weeks >60 ml/min Less than 6 months ago, patient is in a stable state >60 ml/min Less than 6 months ago, patient is potentially in an unstable state New creatinine not needed Within 2 weeks ml/min Greater than 2 weeks Within 2 weeks <30 ml/min Greater than 1 week Within 1 week All outpatients who have none of the risk factors above may be given the recommended full dose of Gadolinium. 12. Imaging patients at risk for NSF: a. If the decision is made to administer Gadolinium to a patient at increased risk for developing NSF, the supervising radiologist should document the reason for the examination and the rationale for use of intravenous Gadolinium b. Group I agents (see above) are contraindicated c. The lowest possible dose of Gadolinium required to obtain the needed clinical information should be used, and it should generally not exceed the recommended single dose. d. If it is necessary to administer Gadolinium to a patient on hemodialysis, the lowest possible dose of Gadolinium should be used. Hemodialysis should be performed as soon as possible after the examination. A repeat hemodialysis session at 24 hours is recommended but not necessary.

7 Use of Gadolinium contrast in patients at risk for developing NSF. egfr > 60 ml/min egfr ml/min egfr <40 ml/min No contraindication to the use of gadolinium contrast agents. The full recommended dose may be used. No special precautions are required. The full recommended dose may be used. Gadolinium should be avoided in these patients. if Gadolinium enhanced MRI is deemed essential, use the lowest possible dose needed to obtain a diagnostic study. Patients already on hemodialysis should receive a dialysis session as soon as possible after the administration of gadolinium.

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