radiological perspective

1. Iodinated Contrast Media
Presentor : Dr Inayat Ellahi
Moderator : Prof. Sheikh Riyaz

2. INTRODUCTION
• widely used pharmaceutical agents in radiology.
• integral part of many diagnostic imaging studies.
• Intravenously ( MC ), intra-arterially, intrathecally, orally and intra-
abdominally.
• ideal qualities of intravascular contrast agents are:
• Water solubility
• Chemical and heat stability
• Biological inertness (non-antigenic)
• Low viscosity
• Lower or same osmolality as human serum
• Selective excretion (i.e. kidney)
• Safety
• Low cost
• free of substances interfering with physiological homeostasis.

3. HISTORY
• In 1920s, the first radiographic contrast medium introduced,
sodium iodide.
• First major breakthrough - iodine was bound to organic
molecules [ uroselectan (Iopax), Uroselectan-B (Neoiopax) ].
• 1960s, majority of water soluble contrast media were salts of
iodinated fully substituted benzoic acid derivatives [tri-
iodinated benzoic acid].
• 1970s, introduction of low osmolar contrast media (LOCM) -
[ iohexol, ioversol,iopamidol and iobitridol ].
• 1980s and 1990s, ongoing development of nonionic isotonic
dimers.

4. BASIC CHEMISTRY
• Basic constituent of all ICM - Tri-iodinated benzene ring.
• Carbon 1 attachment differentiates ionic from nonionic contrast
media.
Ionic media - acidic group with sodium or meglumine
is attached at C1.
Nonionic media - amide group attached at C1.
• C3 and C5 have amide attachments to increase solubility and
also to reduce protein binding.
• Iodine atoms attached at C2, C4, C6.
• Iodine (127) --- higher atomic number.
K-shell electron binding energy (34 keV ).
excellent radio-opacity.

6. Types of ICM
• Based on their osmolality:
• High-osmolar contrast media (HOCM).
• Low-osmolar contrast media (LOCM).
• Iso-osmolar contrasts.
• Based on their ionicity:
• Ionic [ Monomeric , Dimeric ].
• Nonionic [ Monomeric , Dimeric ].

7. • High-osmolar contrast media (HOCM) have more than 1400
mOsm/kg H 2 O osmolality (5-8 times the osmolarity of plasma)
and most of them are ionic.
• Low-osmolar contrast media have 600 to 800 mOsm/kg H2O
(2-3 times the osmolarity of plasma) and consists of both ionic
and nonionic contrast media.
• Iso-osmolar contrasts have osmolality of 290 mOsm/kg H 2 O
(same osmolarity as blood, plasma and cerebrospinal fluid) and
only one product, which is nonionic is currently available.

8. • Ionic monomeric agents:
• Commonly used anions are diatrizoate and iothalamate.
• break up into their anion and cation components in a solution.
• Delivering 3 iodine atoms (3:2 ratio of iodine to osmolar particles).
• relatively high osmolality (>1400 mOsm/kg).
• Meglumine iothalamate, sodium iothalamate, meglumine and sodium
diatrizoate.
• Ionic dimers:
• formed by joining two ionic monomers together and eliminating one
of the carboxyl groups.
• deliver 2 ionic components per 6 iodine atoms (6:2 ratio of iodine to
osmolar particles).
• relatively low osmolality of 600 mOsm/kg at comparable iodine
concentrations.
• Ioxaglate (Hexabrix).

9. • Nonionic monomers:
• most widely used among lower-osmolality contrast agents.
• tri-iodinated benzene ring is made water soluble by the addition
hydrophilic hydroxyl groups to organic side chains.
• do not ionize in solution
• delivers 3 iodine atoms per molecule (3:1 ratio).
• relatively low osmolality (600 to 800 mOsm/kg) .
• iohexol,iopromide, ioversol, iopamidol and iomeprol.

10. • Nonionic dimers:
• delivers 6 iodine atoms per molecule (6:1 ratio).
• most ideal contrast medium.
• higher viscosity and greater resistance to catheter injection.
• iodixanol (Visipaque) - osmolality of 290 mOsm/kg H 2 O,
same as blood.

12. PHARMACOKINETICS
• high water solubility, low lipid solubility, low plasma protein
binding & Small size.
• distributed only in the extracellular fluid and not metabolized.
• Do not Penetrate through the intact cell membrane or into the
interior of the viable cells.
• Once in systemic circulation, the molecules quickly equilibrate
across capillary membranes (except an intact blood-brain
barrier.)
• excreted mainly by glomerular filtration (99%).
• no significant tubular excretion or resorption.
• half-life is approximately 2 hours & can be prolonge to over 30
hours in patients with severe renal dysfunction.
• Readily dialyzable.

13. General Policies for ICM Administration
• Only authorized persons should inject ICM.
• dose and technique decided under the guidance of radiologist.
• stored at less than 37°C for maximum period of one month.
• Multidose bottles discarded if not used within 8 hours after being
opened.
• inspect contrast containers/vials for integrity, signs of contamination
and also check expiry date.
• patients should be observed for sometime in the radiology
department after ICM administration.
• Emergency aid should be readily available.

14. Guidelines for Intravenous Administration
• Intravenous injection - most common parenteral route.
• Contrast injected directly via butterfly needle, an angiocatheter
or through an established IV line.
• If power injector utilized, 22 G or large needle or cannula 1.25"
to 1.5" length is preferred for IV injection.
• Only power-injection rated peripherally inserted central
catheters (PICC) or central lines are approved for power
injection.
• entral line catheters, If not power rated, the contrast injection
must be hand injection.

15. • maximum flow rate and psi set for adult and pediatric
injections are 5 mL/sec at <300 psi and 2 mL/sec at <300 psi
respectively.
• 5 rights for medication administration should be strictly
followed.
• Check serum creatinine levels and glomerular filtration rate
(GFR) before injecting the contrast.

16. Dosage of ICM
• considered as potential risk factor for adverse contrast reactions and
nephropathy.
• lowest dose necessary to obtain adequate visual ization should be
used.
• Standard dose of iodinated contrast administration is 1-2 mL/kg at
concentration of 300 mg/mL.
• maximum limit of contrast administration is typically 200 mL of an
agent with a concentration of 320 mg/mL (a total of 64 gram of
iodine).
• dose may also depend on the individual factor, such as a patient’s
level of hydration.

17. Interaction with Other Drugs and Clinical Tests
• ICM may interact with other drugs and interfere with biochemical
assays.
• essential to be aware of the patient’s drug history.
• Drugs requiring special attention include metformin, cyclosporine,
cisplatin, aminoglycosides, NSAIDS, beta blockers, interleukin-2 and
hydralazine.
• should never be mixed with other drugs in the tubes or syringes.
• Biochemical analysis of blood or urine should be avoided within 24 hour.
• may interfere with some isotope studies.

18. Guidelines for Selective use of LOCM
• American College of Radiology (ACR) guidelines recommends
selective use of LOCM to:
• Patients having history of a previous adverse reaction
to contrast material, except for a sensation of heat
or flushing or a single episode of nausea or vomiting;
• Patients having history of asthma or allergy;
• Patients with history of cardiac dysfunction, including
recent or potentially imminent cardiac decompensation,
severe arrhythmias, unstable angina pectoris, recent
myocardial infarction, and pulmonary hypertension;
• Patients with generalized severe debilitation
• Any other circumstances, such as patients having sickle-cell
disease, increased risk for aspiration, anxious patients, patients
with whom communication cannot be established to know about
the risks, and patients who request for the use of LOCM.

19. Iso-osmolar Dimeric Contrast Media
• Currently available is iodixanol (Visipaque 270 & 320).
• osmolality of 290 mOsm/kg H 2 O, similar to blood.
• Isotonicity and lack of osmotoxicity of these contrast media result in
better renal tolerance.
• lower incidence of adverse events than other nondimeric contrast
media.
• causes less frequent and less intense discomfort on injection.
• Recent studies and clinical trials found no significant reduction in the
risk of CIN with the use of iodixanol, as compared with LOCM.

20. Adverse Reactions
• Though safe and widely used medications, are not completely
devoid of risks, and adverse side effects.
• HOCM (5 to 12%) > LOCM (1-3%).
• mild and moderate contrast reactions occur more frequently
with HOCM (6–8%) than for LOCM (0.2%), but the incidence of
severe reactions remains similar.
• Anaphylactic reactions are more common with HOCM,
whereas cardiovascular decompensation is more common with
LOCM.

21. CONCLUSION
• most widely used.
• Quite safe to use.
• Reactions, when they occur, are usually mild but may
occasionally progress to life-threatening proportions.
• thorough knowledge is essential to minimize the threats posed
by these factors.