2. Introduction
Contrast media - Group of chemical compounds that increase or
decrease the x ray attenuation and therefore increase the
contrast of the structures that contains them
Group - Negative contrast (Air)
Positive contrast (Iodine compounds, Barium)
Iodine is the only element that has proved satisfactory for general
use as intravascular radiological contrast media.
3. History and development
1923
◦ First report of opacification of urinary tract by renal excretion of injected 10% sodium iodide used for
treatment of syphilis
◦ Selectan neutral, - excreted in urine but image quality was poor
1929
◦ Some modification to molecule was done and first intravenous urogram was performed with compound
uroselectan (monoiodinated compound)
◦ Later, Di-iodinated compound (Uroselectan B & Diodone) were developed
1952
◦ First Tri-iodinated sodium acetrizoate (Urokon) was introduced
◦ 6 carbon ring structure, tri-iodobenzoic acid - precursor of all modern water soluble contrast media
4. 1955
◦ Much safer derivative – Diatrizoate (Urograffin, Hypaque) introduced
1962
◦ Iothalamate (Conray)
All conventional contrast media are ionic and had high osmolality (4-7 times of plasma)
Most of the contrast related adverse effects were related to high osmolality of the contrast
Further developments were directed towards reducing the osmality of contrast without
changing the iodine concentration, or even increasing iodine concentration
5. Newer development of contrast proceeded
1. Combine two tri-iodinated benzene rings to produce anion with 6 iodine atoms (Dimeric Diacidic) –
iocarmate
2. Replacement of one carboxylic acid group in dimer with non ionizing radical (Dimeric Monoacidic) -
Ioxaglate
3. Produce compound that doesnot ionize in solution (Monomeric, non acidic) – iopamidol, iohexol,
iopramide, Iopental, Iosversol, Iopramide.
4. Non ionizing Dimeric compound – Iotrolan, Iodixanol
6. Osmolality
Osmolality is the total number of molecule or particle
present in one kilogram of solution
Osmolality of:
◦ Blood/Plasma – 300
◦ Low osmolar contrast media – 400-700
◦ High osmolar contrast media – 1400 – 1800
7. Advantage of LOCM over HOCM
Advantages : Less tissue toxicity
Less adverse effects
Disadvantage: High cost as compared to HOCM
Indication:
◦ In those at high risk of hyperosmolar effects of HOCM eg. Children, Elderly,
Renal or Cardiac failure patients, Poorly hydrated, Diabetics, Sickle cell
anaemia, Multiple myeloma etc.
◦ Those with previous reaction with contrast
◦ Procedures requiring high dose of contrast
12. Patient Preparation
3 H’s
History
◦ Past history of contrast reactions
◦ Asthma, Heart disease, Renal insufficiency, Thyroid disorder,
Diabetes, Myeloma, Sickle cell disease, Paraproteinaemias
◦ Drug history – Metformin, Aminoglycosides
Hydration
Have equipment and expertise ready
13. Adverse events after IV iodinated contrast media
administration
Frequency of adverse events related to intravascular administration
of iodinated contrast media is low and has decreased considerably
with change in usage from ionic HOCM to non ionic LOCM
Majority of adverse side effects are mild and non life threatening
Usually require only observation, reassurance and supportive
measures
Life threatening adverse effects however can occur and usually
noted within 20 minutes of contrast administration
14. Acute adverse events
Allergic like reactions
◦ Identical to anaphylactic reaction to drug or other allergen
◦ Since antigen antibody response cannot be identified they are classified as
“anaphylactoid”, “allergic like”, or “idiosyncratic” reactions
◦ Pathogenesis is unclear, ICM causes release of histamine from basophils and
mast cells
◦ Other possible pathways – activation, deactivation or inhibition of variety of
vasoactive substances (histamine, compliment and kinins)
15. Categories of Reaction
Mild
Signs and symptoms appear self-limited without evidence of progression (e.g., limited urticaria
with mild pruritus, transient nausea, one episode of emesis) and include:
Treatment: Requires observation to confirm resolution and/or lack of progression but usually no
treatment. Patient reassurance is usually helpful.
• Nausea, vomiting
• Altered taste
• Sweats
• Cough
• Itching
• Rash, hives
• Warmth
• Pallor
• Nasal stuffiness
• Headache
• Flushing
• Swelling: eyes, face
• Dizziness
• Chills
• Anxiety
• Shaking
16. Moderate
Signs and symptoms are more pronounced. Moderate degree of clinically evident focal or
systemic signs or symptoms, including:
Treatment: Clinical findings in moderate reactions frequently require prompt treatment. These
situations require close, careful observation for possible progression to a life-threatening event.
• Tachycardia/bradycardia
• Bronchospasm, wheezing
• Hypertension
• Laryngeal edema
• Generalized or diffuse erythema
• Mild hypotension
• Dyspnea
17. Severe
Signs and symptoms are often life-threatening, including:
Treatment: Requires prompt recognition and aggressive treatment; manifestations and
treatment frequently require hospitalization.
• Laryngeal edema (severe or rapidly
progressing)
• Convulsions
• Unresponsiveness
• Profound hypotension
• Cardiopulmonary arrest
• Clinically manifest arrhythmias
18. Treatment of adverse effects following ICM
Mild adverse effects
◦ Iv access should be maintained
◦ Observation
◦ Reassurance
◦ Oral anti histaminics
Severe reactions
◦ 100 % O2 10-15 l/min
◦ Salbutamol nebulization (5mg in 2 ml) for wheeze
◦ Hypotension – Rapid infusion of iv fluids
◦ Bradycardia – Atropine 0.6 mg, can be repeated every 5 minute till maximum of 3 mg
◦ Bronchospasm, urticarial, laryngeal odema – 500 mg of hydrocortisone, 10 mg of chlorpheniramine iv
slowly over 1-2 min,
◦ Life threatening hypotension – Adrenaline 500 µg (0.5 ml of 1:1000) im.
19. Breakthrough Reactions
•Adverse reactions in pre-medicated patients with past history of contrast reactions is called
breakthrough reaction
•Pre-medications decreases frequency of breakthrough reaction
•Breakthrough reactions are less with use of LOCM
•Severe allergy to other drugs or other allergens are at higher risk
20. Premedications
Elective Premedication
Two frequently used regimens are:
Prednisone – 50 mg , PO 13 hours, 7 hours, and 1 hour before contrast media injection
+
Diphenhydramine – 50 mg iv/im/PO, 1 hour before contrast medium .
OR
Methylprednisolone – 32 mg, PO 12 hrs and 2 hrs before contrast media injection.
An anti-histamine (as in option 1) can also be added to this regimen injection
If the patient is unable to take oral medication, 200 mg of hydrocortisone intravenously may be
substituted for oral prednisone.
21. Emergency Premedication
1. Methylprednisolone 40 mg or hydrocortisone 200 mg intravenously every 4 hours until
contrast study required plus diphenhydramine 50 mg IV 1 hour prior to contrast injection
2. Dexamethasone 7.5 mg or betamethasone 6.0 mg intravenously 4h until contrast study must
be done in patient with known allergy to methylprednisolone, aspirin, or non-steroidal anti-
inflammatory drugs, especially if asthmatic. Also diphenhydramine 50 mg IV 1 hour prior to
contrast injection.
IV steroids have not been shown to be effective when administered less than 4 to 6 hours prior
to contrast injection.
22. Organ specific adverse effects
Vascular
◦ Venous –pain at site of injection d/t perivenous injection, pain extending up arm – d/t stasis of contrast,
delayed limb pain – d/t thrombophlebitis
◦ Arterial – endothelial damage
Soft tissue – pain swelling and ulceration d/t extravasation of contrast
Cardiovascular
◦ Intracoronary injection – ventricular fibrillation, arrhythmia, heart block
◦ Increased vagal activation causing bradycardia
◦ Volume overload leading to heart failure, pulmonary odema
23. Hematological
◦ Hemolysis
◦ RBC aggregation and coagulation
◦ Platelet dysfunction, potentiation of heparin
◦ Sickle cell crisis
◦ Transient eosinophilia
Neurotoxicity
◦ Seizures in patients with epilepsy and cerebral tumors or secondary to hypotension following cardiac arrest
◦ Less with LOCM
Thyroid dysfunction
◦ Thyrotoxicosis in patient with non toxic goiter
◦ Interfere with TFT
24. Nephrotoxicity
Incidence of nephrotoxicity following ICM administration is around 5%
Majority of renal impairment are temporary
Predisposing factors :
◦ Pre existing renal impairment (present in 90%)
◦ Diabetes mellitus
◦ Dehydration
◦ Age
◦ Dose of contrast
◦ Multiple myeloma
◦ Other nephrotoxic drugs (Aminoglycosides, NSAIDs, Metformin)
25. Mechanism of renal impairment – exact pathophysiology not known
◦ Hypoperfusion of kidneys
◦ adverse cardiac effects leading to Increased vasodilation
◦ Predehydration
◦ Osmotic diuresis
◦ Glomerular injury and tubular injury
◦ Impaired perfusion
◦ Chemotoxic effect of contrast
◦ Obstructive nephropathy
◦ Precipitation of Tamm-Horsfall protein
◦ Precipitation of Bence jones protein
26. Diagnosis
◦Increase in 25 – 50% of baseline creatinine level
◦Increase in 0.5 mg/dl of creatinine
Acute kidney injury network (AKIN) criteria
◦Following findings within 48 hours of nephrotoxic event
1. Absolute serum creatinine increase of >0.3 mg/dl
2. Percentage increase in creatinine ≥ 50 % above baseline
3. Urine output reduced to ≤ 0.5 ml/kg/hour for at least 6 hrs
27. Contrast extravasation
•Incidence 0.1 – 0.9 %
•Can occur during hand or power injection
•Initial sign and symptoms – swelling or tightness, stinging or burning pain,
edematous erythematous and tenderness at site of extravasation
•Sequelae – causes local acute inflammatory response esp. to skin peaks in 24 –
48 hrs
•Usually no permanent injury
•Most common severe injury - compartment syndrome
•Others – skin ulceration, tissue necrosis
28. Treatment
◦ No clear consensus
◦ Elevation of limb
◦ Hot/cold compression
◦ Aspiration of extravasated contrast
◦ Surgical consultation for severe injuries eg. Compartment syndrome or symptoms – progressive
swelling, altered sensation, decreased capillary refill time, skin ulceration or blistering
Risk for extravasation
◦ Infants, elderly and debilitated patients who cannot communicate effectively
◦ Patients with vascular diseases – atherosclerosis, thrombosis, radiotherapy, diabetics
◦ Vascular sites – hand and wrist, foot and ankle
◦ Contrast injection through indwelling catheter placed more than 24 hrs
30. Contrast in children
•Neonates and small children are more susceptible to fluid
shifts hence have lower tolerance for osmotic load
•Small caliber iv cannula cause difficulty in injection viscous
contrast media
•Usual dosing – 2ml/kg, injected at slower rate – 1.5ml/s
31. Metformin and ICM
•Iodianted contrast is not an independent risk factor for patient taking Metformin, but is of
concern in presence of underlying conditions of delayed renal excretion of metformin
•No reports of lactic acidosis following ICM in properly selected patients
32. ACR committee recommendations
◦ Category I – normal renal function and no known comorbidities
◦ No need to discontinue metformin
◦ No need check creatinine before resuming the metformin after 48 hrs of ICM administration
◦ Category II – apparently normal renal function but with multiple
comorbidities
◦ Discontinue the metformin at time of examination and withheld for 48 hrs
◦ No need to check creatinine if clinically stable and no other risk factors of renal damage (
aminoglycoside treatment, surgery, sepsis)
◦ Category III – patient with renal dysfunction
◦ Withheld metformin and cautious follow up of renal function should be performed until safe
reinstitution of metformin can be assured
33. Dialysis patients
•Can receive intravenous contrast media
•Theoretical risk of converting oliguric dialysis patient to anuric
dialysis patient, increased vascular load
•Contrast agents are not protein bound and are easily cleared by
dialysis
•Unless significant volume of ICM injected or underlying cardiac
dysfunction – no need for urgent dialysis
34. Pregnancy
•Iodinated contrast media crosses the placenta and enter fetus in
measurable quantities
•Limited studies about effects of ICM to human embryo
•Animal studies show no evidence of either mutagenic or teratogenic
effects with LOCM
•Considering the radiation risk and unknown risk of ICM, contrast
studies during pregnancy should only be done if,
◦ No other modalities available
◦ Information from the investigation affects the patient care drastically
◦ Investigation cannot be delayed till the end of pregnancy
35. Breast feeding
Limited studies show
◦ Less than 1% of administered ICM is excreted via breast milk
◦ Less than 1% of contrast medium in breast milk ingested by an
infant is absorbed
◦ 0.01 % administered ICM absorbed by infant, which is below the
safe level of 2ml/kg
◦ Only theoretical possibility of adverse effects
◦ Safe for breast feeding mothers to feed following contrast
investigation
36. Summary
•Contrast Media
•History and Development
•HOCM / LOCM – Disadvantages Vs Advantages
•Indications of contrast studies
•Adverse Reactions
•Treatment of contrast reactions
•Break through reactions – Mx
•Organ specific adverse reactions
•Special considerations
37. References
ACR Manual on Contrast Media, Version 8, 2012
Radiological Procedures, Chapman
Textbook of Diagnositic Imaging, D. Sutton
