Iodinated contrast media

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. N onionic 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.

5. Types of ICM B ased on their osmolality : High- osmolar contrast media (HOCM). Low- osmolar contrast media (LOCM). Iso-osmolar contrasts. B ased on their ionicity : I onic [ Monomeric , Dimeric ]. Nonionic [ Monomeric , Dimeric ].

6. 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.

7. 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 ).

8. 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 .

9. 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.

10. 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.

11. 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.

12. 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 .

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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 .

19. 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.