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.
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
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
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
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.
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.
#3: Light = X-Ray in X-Ray/CT/Fluoroscopy, Radio in MRI
#6: 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
#7: 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
#8: 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.
#9: Combination Exams are ordered separately but done at the same time, usually for older children and for exams that arent available as a pre-set combo
Maximum combined dosage = 150ml
#10: 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.
#17: Polycythemia = Abnormally high hemoglobin due to reduction in plasma volume OR increase in red cell numbers
#18: 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
#19: 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
#20: 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
#21: Cystic Fibrosis increases the risk of blockage in the small bowel
Dehydration can cause/exacerbate constipation
#23: 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+
#24: Left: Omniscan (Gadodiamide)
Right: Dotarem (Gadoterate meglumine)
Neither is on formulary
#25: 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
#26: Gadolinium deposition in brain tissue has been observed.
Unknown what causes it and what effects it has
#27: 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