Contrast Media
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This document compares and contrasts different types of radiopharmaceutical contrast agents. It discusses iodine-based contrast media used for CT scans, including differences between ionic and nonionic monomers and dimers. It also covers barium-based contrast agents used for fluoroscopy of the GI tract and gadolinium-based contrast agents used for MRI. For each type, the document describes the different agents, dosing, administration routes, adverse effects and precautions. The goal is to provide an overview on selecting the appropriate contrast media for diagnostic imaging procedures.
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Contrast Media
- 1. Comparing and CONTRASTing Radiopharmaceuticals LIBBY DAUGHERTY, PHARM.D. CANDIDATE MATTHEW POST, PHARM.D., BCPPS UNIVERSITY OF GEORIGA – APPE 4 – EMERGENCY MEDICINE CHILDREN’S HEALTHCARE OF ATLANTA AT SCOTTISH RITE SEPTEMBER 30, 2016
- 2. Radiography Crash Course Procedures X-rays Computed Tomography (CT) Scans Contemporary Fluoroscopy Magnetic Resonance Imaging (MRI) Ultrasound Contrast Media AKA Contrast Agents, Materials, Dyes Substances that temporarily change the way light interacts with the body and/or detectors. Increase the contrast of targeted areas of the body on imaging.
- 3. Types of Contrast Media Iodine-Based Given orally, rectally or IV Used to enhance contrast on CT scans on all parts of the body, including fluoroscopy Barium-Based Given orally or rectally to image the GI tract Used to enhance contrast during fluoroscopy Gadolinium-Based Given IV only Paramagnetic Alters the magnetic properties of water molecules, enhancing the contrast of MRIs
- 5. Iodine-Based Contrast High Osmolality Contrast Media (HOCM) >900 mOsm Oral only, cannot be used IV Low Osmolality Contrast Media (LOCM) < 900 mOsm is tolerable < 600 mOsm is pain/irritation-free ~ 260 mOsm is “Iso-osmolar” Least irritating Generally reserved for Sickle Cell patients
- 6. Iodine-Based Contrast Ionic Monomer • 3:2 Ratio • High Osmolality Nonionic Monomer • 3:1 Ratio • Low Osmolality Ionic Dimer • 6:2 (3:1) Ratio • Low Osmolality Nonionic Dimer • 6:1 Ratio • “Iso-Osmolar”
- 7. Iodine-Based Contrast Media Iohexol (Omnipaque) Nonionic monomer IV and Oral Iodixanol (Visipaque) Nonionic dimer IV only “Iso-Osmolar” for sickle cell patients Ioversol (Optiray) Iopamidol (Isovue) Ethiodized Oil (Lipiodol) Lipid-soluble Niche use for lymphography IV Dosing is weight-based Dosing is in ml/kg (NOT mg/kg) Concentrations are standard Omnipaque 300 Omnipaque 350 Visipaque 320 Oral Dosing is age-based Omnipaque 180 Omnipaque 300
- 8. Iodine: IV Dosing Single Exams CT Neck 1.5 ml/kg CT Chest 1.5 ml/kg CT Face/Orbits 1.5 ml/kg CT Head 1.5 ml/kg CT Chest/Abd/Pelvis 2.0 ml/kg CT Abd/Pelvis 2.0 ml/kg Combination Exams CT Neck 1.0 ml/kg CT Chest 1.0 ml/kg CT Neck 1.0 ml/kg CT Chest/Abd/Pelvis 2.0 ml/kg CT Neck 1.0 ml/kg CT Abd/Pelvis 2.0 ml/kg Maximum combined dose = 150ml
- 9. Iodine: Oral Dosing Newborn 3-6 M 6-9 M 1-2 Y 3-4 Y 5-8 Y 9-11 12-13 Y 14 Y 15 Y 16+ Y First Dose 2 ml 4 ml 4 ml 5 ml 10 ml 12 ml 15 ml 17 ml 20 ml 30 ml 40 ml Second Dose 1 ml 2 ml 2 ml 4 ml 5 ml 6 ml 8 ml 9 ml 10 ml 15 ml 20 ml Agent Omnipaque 180 Omnipaque 300 First Dose • Given 90 minutes prior to scan • Diluted 1:24-30 Second Dose • Given 30 minutes prior to scan • Approximately 50% of the first dose (80% in 1-2 Y/O) • Diluted 1:22-30
- 10. Iodine: Adverse Reactions Extravasation Nephrotoxicity Lactic Acidosis Contrast Reactions (AKA Contrast “Allergy”)
- 11. Iodine: Nephrotoxicity Contrast-induced nephropathy Iodine-based contrast media can increase serum creatinine by >25% Occurs in 2-7% of cases Risk Factors Pre-existing renal dysfunction (5-10x more likely) Dehydration CHF Concomitant nephrotoxic drugs NSAIDs Aminoglycosides
- 12. Iodine: Lactic Acidosis Renal clearance of Metformin is decreased with renal insufficiency SCr ≥ 1.4 (males) SCr ≥ 1.5 (females) Even temporary renal insufficiency (contrast-induced nephropathy) can precipitate lactic acidosis Mortality rate of up to 50% Metformin must be discontinued at least 48 hours before and after contrast media use
- 13. Iodine: Contrast Media “Allergy” Epidemiology Ionic contrast agents are used in more than 10 million procedures every year Reactions occur in ~10% of procedures 1 in 1000 (0.1%) are severe reactions Unknown Mechanism Not a true allergy (no anti-contrast antibody) Not caused by iodine, not the same thing as an iodine allergy Not related to shellfish (commonly believed myth) Delayed reactions can occur hours-days later, but are generally mild.
- 14. Iodine: Contrast Media “Allergy” Mild Nausea and Vomiting Headache Itching Flushing Mild Urticaria Moderate Severe Urticaria Wheezing/SOB Arrhythmias Hypo/Hypertension Severe Anaphylaxis Respiratory distress Cardiac arrest Angioedema Severe hypotension Seizures
- 15. Premedications Indicated for “high risk” patients: Documented allergic reaction to contrast agent Multiple allergies Asthma/Hay Fever Prednisone 0.5-0.7 mg/kg (max 50mg) PO Given at 13, 7, and 1 hour prior to contrast injection Diphenhydramine 1.5 mg/kg (max 50mg) PO Given 1 hour prior to contrast injection
- 16. Iodine: Precautions Disease States Heart disease Renal insufficiency or failure Sickle Cell Anemia Polycythemia Myeloma Medications Beta blockers NSAIDs Interleukin Methotrexate Metformin
- 18. Types of Fluoroscopy Barium Sulfate Barium enema (Large Bowel) Single and Double (DCBE) Barium swallow (Esophagus/Upper GI) AKA Oral Pharyngeal Motility Study (OPMS) Barium meal (Stomach) Barium follow/pass through (Stomach and Small Bowel) Voiding Crystalurethrography (VCUG) Iodine Diatrizoate Meglumine (Crystografin) Voiding crystalurethrography (VCUG) Diatrizoate Meglumine/Diatrizoate Sodium (Gastroview) GI/NJ Tube Injection Iothalamate Meglumine (Cysto-Conray) Voiding crystalurethrography (VCUG) Enema Iohexol (Omnipaque) 180 and 240 Port Check
- 19. Barium-Based Contrast Brand Barium Concentration Formulation Route Area Imaged Readi-cat Low (2%) Suspension Oral All GI, CT Varibar Thin Honey Medium (40%) Suspension Oral OPMS Varibar Thin Liquid Medium (40%) Powder Oral OPMS E-Z Paque Medium (60%) Suspension Oral Upper GI E-Z Paste Medium (60%) Cream Oral Upper GI E-Z HD High (98%) Suspension Oral OPMS Polibar ACB High (96%) Suspension Rectal Large Intestine • Various concentrations and formulations of Barium Sulfate are used depending on the patient (ability to swallow, etc) and what area is going to be imaged. • Dosages are age-based, differ for each agent, and can be found in the CHOA Fluoroscopy guidelines on Careforce.
- 20. Barium-Based Contrast Media Adverse Reactions Stomach cramps Diarrhea Nausea Vomiting Constipation Allergic reaction (rare) Precautions Cystic Fibrosis Dehydration Ileus GI Perforation
- 22. Gadolinium-Based Contrast Paramagnetism Increases the magnetic moment parallel to an applied external field Causes radio waves to be amplified in those areas which creates contrast Gadolinium is by far the most paramagnetic element Toxicity Free Gadolinium is a toxic heavy metal with physical properties similar to Calcium and can act as a calcium channel blocker. Gadolinium molecules are chelated to create a stable complex that is both paramagnetic and nontoxic. Characteristics which affect the stability of chelated molecules include Structure and Charge
- 23. Gadolinium-Based Contrast Structure Macrocyclic molecules fully enclose the Gadolinium ion and are more stable. Linear molecules are “open chain” and more easily disassociate in the body. Charge Ionic molecules are more stable due to electrostatic forces Nonionic molecules are less stable Least Stable • Linear • Nonionic Most Stable • Macrocyclic • Ionic
- 24. Gadolinium Generic Name Brand Structure Charge Dose Gadopentetate dimeglumine Magnevist Linear Ionic 0.2 ml/kg Gadoteridol Prohance Macrolytic Non-ionic 0.2 ml/kg Gadobenate dimeglumine Multihance Linear Ionic 0.2 ml/kg Gadobutrol Gadavist Macrolytic Non-ionic 0.1 ml/kg Gadoxetate disodium Eovist Linear Ionic 0.1 ml/kg Max dose of 20 ml Administered at a max rate of 10ml/15s
- 25. Gadolinium: Adverse Events Generally well tolerated with mild, self- limiting adverse events Nausea and vomiting Headache Urticaria Allergic reactions are rare Gadolinium deposition in brain tissue Severe reactions can occur Anaphylactoid reactions Nephrogenic Systemic Fibrosis
- 26. Nephrogenic Systemic Fibrosis Occurs when gadolinium molecules are not eliminated properly or quickly enough, generally due to renal dysfunction Dissociation of gadolinium from its chelate activates circulating fibrocytes and initiates a fibrotic cascade Development of fibrous tissue in skin and other tissues Inhibition of joint flexion Hyperpigmentation , thickening and hardening of the skin May improve with improved renal function, but not always the case Treated with photophoresis, thalidomide and plasmapheresis, but these are not always effective
- 27. Gadolinium: Precautions Previous allergic reactions to contrast media Multiple allergies Renal insufficiency or failure Significant cardiac disease
- 28. Clinical Relevance: What to Verify Patient has no contraindications Disease states Concomitant Medications Contrast agent is appropriate for the procedure to be performed Right drug (High vs Low Osmolality) Right route (IV vs Oral vs Rectal) Correct dosage Premedication has been given if necessary Right drugs Right doses Right times
- 29. References Brown, Jeffery. "The Pharmacist's Role in Promoting the Safe Use of Gadolinium-based Contrast Agents: Overview of Best Practices." American Society of Health-System Pharmacists Continuing Education. 27 June 2016. Web. 21 Sept. 2016. Daniel Chernoff. "Principles of Magnetic Resonance Imaging." Ed. Nestor L. Muller and Susan B. Yeon. UpToDate. Wolters Kluwer, 2 Mar. 2016. Web. 30 Sept. 2016. Hong, Sandra J. "Immediate Hypersensitivity Reactions to Radiocontrast Media: Clinical Manifestations, Diagnosis, and Treatment." Ed. N. Franklin Adkinson and Anna M. Feldweg. UpToDate. Wolters Kluwer, 16 Oct. 2015. Web. 30 Sept. 2016. Kent, Ed. "Best Practices in the Use of Iodinated Contrast Media in the Clinical Setting: What the Pharmacist Needs to Know." American Society of Health-System Pharmacists Continuing Education. 28 Mar. 2016. Web. 21 Sept. 2016. Radiological Society of North America (RSNA) and American College of Radiology (ACR). "Contrast Materials." Patient Safety. Radiological Society of North America, Inc., 17 Mar. 2016. Web. 30 Sept. 2016. Rudnick, Michael R. "Prevention of Contrast-induced Nephropathy." Ed. Paul M. Palevsky and Alice M. Sheridan. UpToDate. Wolters Kluwer, 18 Mar. 2016. Web. 30 Sept. 2016.
- 30. Questions? Thank you for your time and attention!
Editor's Notes
- Light = X-Ray in X-Ray/CT/Fluoroscopy, Radio in MRI
- The only agents used in Conventional CT at CHOA are LOCM. There are 3 HOCM used exclusively in Fluoroscopy CT, and we will discuss them later. LOCM can be 10x the cost of HOCM, which used to present a problem for many hospitals The high incidence of adverse effects from administering HOCM (or any agent >600 mOsm) IV outweigh any potential cost-saving
- Ratio of Iodine atoms to molecules Ionic compounds will have two-word generic names Iodine molecule (Anion) Meglumine or Meglumine sodium (Cation) CHOA only uses nonionic compounds IV Ionic dimers have low osmolality and can be used IV but there is no point to keep them on formulary
- Optiray and Isovue are both on formulary but are not actually used according to the radiology department and CHOA guidelines. Ethiodized oil has very niche usage. Visipaque is the only nonionic dimer.
- “Combination Exams” are ordered separately but done at the same time, usually for older children and for exams that aren’t available as a pre-set combo Maximum combined dosage = 150ml
- These dosages (and their specific dilutions) are laid out in the CHOA guidelines for Oral Contrast Media on Careforce. If you want a quick reference, you may like their version of the chart more than this one.
- Extravasation occurs when HOCM is used IV
- CIN risk score Generally temporary and self-limiting
- Specific reaction that occurs with Metformin
- Polycythemia = Abnormally high hemoglobin due to reduction in plasma volume OR increase in red cell numbers
- Barium is an excellent media for enhancing X-Rays of the GI tract because: Inherently radiopaque. Not absorbed Not metabolized Excreted unchanged in the feces Administered only by the oral or rectal route. Barium is insoluble Acts like a clot when administered IV, very serious
- These iodine-based media are mostly ionic (HOCM) LOCM can all be used orally as well, but Omnipaque is the only one with FDA approval and oral formulation
- Various concentrations and formulations of Barium sulfate are used depending on the patient (ability to swallow, etc) and what area is going to be imaged. There are more formulations listed in the CHOA guidelines, but these are the ones that are actually used at CHOA according to Radiology department Upper GI = thick/dense formulations, can be seen on conventional x-ray and fluoroscopy CT = less dense The thin barium is cannot be seen well on x-rays Thick barium can ruin CT images
- Cystic Fibrosis increases the risk of blockage in the small bowel Dehydration can cause/exacerbate constipation
- Gadolinium is more than twice as paramagnetic as the next closest element (Manganese) There are concerns that gadolinium can deposit in brain tissue Physical block of calcium channels, not chemical: free Gadolinium takes the form of Gd3+ ions which have similar molecular radius as Ca2+
- Left: Omniscan (Gadodiamide) Right: Dotarem (Gadoterate meglumine) Neither is on formulary
- Ablavar (Gadofosveset trisodium) had been discontinued and is no longer available commercially. Eovist (Gadoxetate disodium) is lipophilic and is specifically used for liver imaging. Eliminated 50% renally, 50% hepatically. There is a Macrolytic Ionic agent called Dotarem (Gadoterate meglumine). Newest agent, approved in 2013 Several orders of magnitude more stable than other GBCAs Not on formulary
- Gadolinium deposition in brain tissue has been observed. Unknown what causes it and what effects it has
- Gadolinium molecules are ticking time-bombs. They are only stably chelated for a certain length of time, and then the free gadolinium is set loose. If gadolinium agents are not eliminated before they are broken down, then free gadolinium can cause NSF Most gadolinium molecules undergo renal elimination Gadobenate dimeglumine (Magnevist) has 4% hepatic elimination Gadoxetate disodium (Eovist) has 50% hepatic elimination