- Conventional ionic contrast media
- Low osmolar, non-ionic contrast media
- Advantages of non-ionic vs ionic contrast agents
Conventional ionic
contrast media
- diatrizoate, iothalamate, metrizoate
- monomeric salts of tri-iodinated benzoic acid with substituted side-chains at positions 3 and 5; iodine atoms at 2,4 and 6; cation at position 1.
- anion is the radiopaque portion but both the anion and cation
are osmotically active therefore the solution will be hypertonic
to plasma
- could be made isotonic to plasma but at this dilution the iodine concentration would be only 6% and not useful as contrast agent
- Side effects from ionic contrast agents
- Hypertonicity
- Main reason for side effects - 5-8x tonicity of plasma - severe physical insult to body regardless of the nature of the chemical injected.
- endothelial lesions in blood vessels - desiccation and weakening to intracellular bonding, increased capillary permeability and risk of thrombus formation
- damage to BBB: increased permeability of cerebral capillaries results in toxic molecules affecting nerve cells
- RBC/blood flow: water drawn from RBC which becomes deformed and rigid and may not be able to pass through capillary beds - can cause thrombosis/ischemia esp. in brain and myocardium
- cardiovascular effects: vasodilation both local and
generalized
- local effects: flushing, sensation of warmth, discomfort
- generalized: hypotension
- in man, the effects are directly proportional to the tonicity
- problems may be greater in patients with congestive heart failure
- renal effects: diuresis usually induced in most patients
after IV injection due to increase in serum osmolality
- acute renal failure is unusual but well recognized complication of these agents. Probably due to hypertonicity and direct chemical toxicity to kidney
- predisposing factors: renal insufficiency, dehydration, congestive heart failure, diabetes mellitus, multiple myeloma
- side effects (human descriptions): nausea, vomiting, fever, chills, faintness, headache, sneezing, perineal discomfort, metallic taste
- Ionic charge
- effects on local electrolyte balance
- effect nerve conduction
- cardiac effect (esp. from high sodium load)
- Chemical toxicity
- inherently toxic molecule, esp. the sodium salt - cardiac, hepatic, and renal disease patients are esp. susceptible to increases in sodium
- peripheral vasodilation and other side effects are increased when the sodium concentration increases
- methylglucamine (meglumine) salt is less toxic but has increased viscosity which is why the two are often mixed to reach a compromise between toxicity and viscosity
- occasional toxicity found from iodinated anion or free I released
- toxicity may occur from protein binding - esp. enzyme
binding
- acetylcholinesterase inhibition is measured as an indicator of toxicity
- toxicity inversely proportional to degree of hydrophilia and in conventional agents the highly hydrophobic iodine atoms are relatively exposed due to short side chains
- most sensitive organs are heart, brain and kidney
- effect on BBB from sodium cation and carboxyl group of the
anion as well as hypertonicity
- acute tubular necrosis can occur
- cardiotoxicity can be fatal
- Allergic/Anaphylactic reactions
- In humans, about 5% have some hypersensitivity reaction in minutes or delayed by hours.
- Mechanism unknown but increased reactions in allergic or asthmatic people and those with heart disease
- reactions range from sneezing - urticaria - pharyngeal - cerebral - or pulmonary edema - bronchospasm - to fatal cardiovascular collapse
- in man - 1/40,000 fatality rate
- Hypertonicity
-
Low osmolar, non-ionic contrast media
- metrizamide, iopamidol, iohexol
- tri-iodinated substituted ring compound - do not dissociate in solution so that hypertonicity is avoided. Side chains have been altered to make molecule highly hydrophilic to increase solubility without dissociation
- Increased ratio of iodine per osmotic particle (3:2 for ionic)
vs (3:1 for non-ionic)
- osmolality halved (non-ionic)
- actually reduced further by tendency for molecules to aggregate in solution
- results in osmolality 1/3 of ionic contrast media and decreased side effects
- Can be used for intravenous or intrathecal injections but due to expense (about 10x ionic) usually reserved for myelography
- Image quality depends on iodine concentration and total iodine
delivered
- clarity/definition requires accumulation of contrast agent
- osmotic dilution of the low osmolar agents by body fluids is much less and occurs more slowly than with hyperosmolar agents resulting in sharper images for longer times
-
Advantages of non-ionic vs ionic contrast agents
- Reduced tonicity: since most side effects are related to hypertonicity, the change to nearly isotonic has significantly decreased reactions in man - some studies report dramatic decrease in side effects and discomfort largely due to reduction in vasodilation and resultant sensations of heat and flushing
- Myelography: cannot use ionic contrast media for myelogrpahy so discovery of non-ionic in 1974 (metrizamide) revolutionized this procedure. Newer agents (iopamidol and iohexol) have even lower neurotoxicity
- Chemical toxicity: molecules are more hydrophilic due to longer sidechains, shields the hydrophobic I atoms, no sodium ions, decreased damage to BBB. Increased hydrophilia means less tendency to cross cell membranes
- Decreased hypersensitivity reactions: fatal reactions in man reported - 1/80,000 - probably most from decreased osmolality and decreased cardiotoxicity
Fig. 2. The a, osmolality (mOsm/kg water) and b, viscosity at 37 °C of currently available iodinated contrast media. The values in the bars show the iodine content (mg/mL). The ionic HO media are shown in green, the ionic LO medium in red, the non-ionic LO media in light green and non-ionic iso-osmolar media in light red.
Thomsen, H.S. & Morcos, S.K. (2000)
Radiographic contrast media.
BJU International 86 (s1), 1-10.
Available from: http://dx.doi.org/10.1046/ j.1464-410x.2000.00586.x
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