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Contrast media

About iodinated contrast

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Contrast media

  1. 1. Radiographic Contrast Media I 1 Presenter: Seema Dixit Bsc MIT 2015 BPKIHS
  2. 2. Contents • Introduction • Historical development • Basic chemistry • Classification • Risk factor • Adverse rxn and management • Premedication • Golden rules • Emergency equipment 2
  3. 3. Contrast Media A “contrast medium” or “dye” is a liquid/solid substance that is used during a radiological examination for the purpose of delineating internal structures or an organ that is being studied, this would otherwise not be possible. IDEAL CHARACTERISTIC Water-soluble Heat/Chemical/Storage Stability Non-antigenic Low viscosity Lower or same osmolarity compared to plasma Selective excretion Low cost 3
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  5. 5. Historical development • 1896-Haschek and Lindenthal performed angiogram on amputated hand. and Hicks and Addison performed angiogram on cadaver kidney. • 1923- Barberick and Harsih used strontium bromide solution for opacification of peripheral veins • Osborne noted opacification of bladder in patients treated with i.v. sodium iodide for Syphilis. • 1924 Brook- tried sodium iodide solution for pripheral angiography. • Moniz- used sodium iodide solution to carotid angiography. • 1925 – Binz and Rath began synthesis of pyridine derivatives containing iodine. – Selectan Neutral, Uroselectan. • Later they synthesised di-iodonated pyridines of higher solubility. 5
  6. 6. • 1953-Wallingford showed that an amino group at C3 position allowed side chain such as acetyl (COCH3) to replace one of its hydrogen atoms. • This acetyl- amino group greatly reduced the toxicity of tri-iodo compound. • Thus first tri-iodonated contrast medium Sodium–acetrizoate ( Urokon) was introduced clinically by Mallinckrodt 6 COOH NHCOCH3 I I I
  7. 7. • 1956- Hoppe and colleages showed that a second acetyl – amino group could be added to benzene at C5 to produce a fully substituted tri iodinated radical. • This reduced the toxicity even further. 7 •This compound sodium diatrizoate (Urograffin) was introduced for clinical use. 7 COOH NHCOCH3 I I I CH3CONH
  8. 8. • 1968 – Torsten Almen – suggested that reducing osmolality of contrast media by substituting non radio opaque cation with a non ionizing amide. • 1969 – Nyegaard research group produced first low osmolar contarst agent Metrizamide ( Amipaque) which was glucose amide of metrizoate. • 1970 – Metrizamide was replaced by second generation low osmolar contrast agent - Iohexol and Iopamidal. Till today they have remaimned among the intravascular contrast agents of choice. 8
  9. 9. 9 Contrast Media X-Ray & CT Ultra Sound MRI Negative CM Air,CO2 Positive CM BaSO4 Oily CM Iodinated CM Water soluble
  10. 10. 10 Iodinated CM Water soluble Renal ExcretionHepatic Excretion Iopanoic Acid Calcium Iopadate Low OsmolarHigh Osmolar Nonionic diamers Iodixanol Non-ionic monomers Metrizamide Iohexol Ionic diamers Ioxaglic acid Iocamic acid Ionic Monomers Iothalmate Diatrizoate
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  12. 12. BASIC CHEMISTRY • Triiodinated benzene ring is the basic constituent of all CM. • Benzene ring has 6 carbons numbered 1 to 6 clockwise. • Carbon 1 attachment differentiates ionic from non ionics. • Iodine attached at position 2,4,6 carbons. • C3 and C5 have amide attachments to increase solubility and and also to reduce protein binding. • At C1 in ionics acidic group with sodium or meglumine is attached . • At C1 in non ionics amide group is attached. 12
  13. 13. Classification of Iodinated CM Iodine to particle ratio Osmolarity of 280 mg I per ml solution Monomer Ionic; ditrizoate metrizoate iothalamate 1.5 1500 Non Ionic; iopamidol Iohexol Iomeprol Ioversol Iopromide 3 470 Dimer Ionic ;ioxaglate 3 490 Non Ionic ;Iotrolan Iodixanol 6 300 13
  14. 14. HOCM: Chemical Structure • These are salts consisting of -> – Tri-iodinated benzoic acid anion with – Na+ or Methylglucamine (meglumine) cation. 14 RR II I COO-- Na/Meg+ Monomeric and Monoacid Eg: Ionic Monomers Iothalmate Diatrizoate Iodine particle ratio 3:2
  15. 15. Diatrizoate • INCRESAES Solubility • Decreases plasma protein binding there by increaseing its ability to be filtered in glomerulus • Improves patient tolerence 15 NHCOCH3 II I COO-- NHCOCH3 Eg: Urograffin, Angiogrffin, Trazogrff, Urovision,Urovideo Na/Meg+
  16. 16. Iothalmate • Better neural tolerance • Decreased CVS tolerence 16 COOHR II I COO-- Na/Meg+ Eg: Conray, Triovideo.
  17. 17. Ioxaglic acid: Hexabrix 17 R II I COO-- R II I R R Na+ Meg- Dimeric -monoacid IP ratio 6:2
  18. 18. Non-ionic Monomers 18 RR II I COO-- Na/Meg+ R:non ionizing radicle Eg: Metrizamide Iohexol (Omnipaque) Iopamidol (Iopamiro) Ioversol (Optiray) Iopromide (Ultravist) IP ratio 3:1 Monomeric-non-ionic
  19. 19. Non-ionic Dimers 19 ROH II I ROH HOR II I ROH R IP ratio 6:1 Dimeric-non-ionic Eg: Iodixanol
  20. 20. Why iodine? – Relatively safe :Low toxicity – High contrast density d/t high atomic number(53) – K edge (binding edge of Iodine K-shell electron)=32 keV • K edge close to mean energy of diagnostic x-ray • Results in increased K-shell interactions = great x-ray absorption = great subject/background contrast – Allows firm binding to highly variable benzene ring. Disadvantages of HOCM High osmolality 5- 8 times plasma osmolality. Responsible for their adverse effects. Advantage of LOCM -less tissue toxicity -reduction in adverse reactions. 20
  21. 21. Iodinated Contrast Media • Ionic • Nonionic
  22. 22. Osmolality • -is the total number of particles in solution per kilogram of water. • As osmolality reduces towards physiologic range tolerance of the contrast meadia increases. • HOCM in solution (ionized form) has two ions with only one carrying the iodine. Thus for conc of 1 mol/L, the osmolality is 2 osm/L. 22
  23. 23. Methods of Administration of Contrast Material • INGESTED / INSTILLED – (ORALLY OR RECTALLY) • INJECTED – IV – INTO BLOOD VESSELLS • RETROGRADE – AGAINST NORMAL FLOW (Vessels & Organs) • INTRATHECAL – Spinal canal • PARENTERAL (IV, Intrathecal) – Injecting into bloodstream – (anything other than oral)
  24. 24. Risk factor• Allergy • Asthma • Renal insufficiency(contrast induced nephrotoxicity) • Anxiety • Cardiac status( angina, CHF, aortic stenosis etc) • Pregnancy • Miscellaneous risk factor; - multiple myeloma are known to irreversible renal failure after HOCM administration due to tubular protein precipitation and aggregation and no rsk with the use of LOCM. -In Infants and neonates contrast volume is important consideration because of low blood volume -patient with pheochromocytoma develop an increase in serum catecholamine level after iv. Inj of HOCM but safe in non ionic contrast media. -hyperthyroidism may develop iodine-provoked delayed hyperthyroidism.Effect appear 4 to 6 wks after iv contrast(iodinated) administration. It is usually self limited. -Diabetes maellitus (Metformin is discontinued at the time of investigation and withheld for subsequent 48h. 24
  25. 25. Adverse reactions • Predictable/Chemo toxic reactions – Direct effect on specific organs and systems – Dependent on dose, molecular toxicity, physiochemical properties of CM • Unpredictable/ Anaphylactic reactions (Idiosyncratic, psedoallergic, allergic-like, anaphylaxis-like) – abnormal reactivity of individual to active mediators – Independent of dose 25
  26. 26. Predictable reactions • Affects specific organs and systems – Soft tissues – Cardiovascular • Venous • Arterial • Cardiac – Renal – CNS – Hematological – Endocrine • thyroid 26
  27. 27. Chemo toxic reactions on Soft tissues Effect Prophylaxis Management Pain/Swelling/Ery hema Chemical cellulitis Venous thrombosis Compartment Use of nonionic LOCM Careful cannulation Close observation of power inj Conservative Analgesic, arm elevation, cold pack Surgery for compartment syndrome Hyluronidase 27
  28. 28. Chemo toxic reactions on Cardiovascular system-Venous sys Effect Prophylaxis Management Pain, stasis, Throbophlebitis Good cannulation Use of low sodium, nonionic LOCM Conservative Arm elevation Encourage arm movement 28
  29. 29. Chemo toxic reactions on Cardiovascular system-Arterial sys Effect Prophylaxis Management Pain, heat d/t vasodilatation Endothelial damage Use of LOCM Conservative Reassurance 29
  30. 30. Chemo toxic reactions on Cardiovascular system- Cardia Effect Prophylaxis Management Arrhythmias Hypotention Vasovagal reaction Pulmonary oedema Use of nonionic cotrast media Caution in any low out put state, left ventricular failure, severe coronary artery disease, unstable angina Cardiac- resuscitation measures 30
  31. 31. Chemo toxic reactions on renal sys Effect Prophylaxis Management Transient rise in serum creatinine Persistent dence nehrogram Rarely fatal/persisting Avoid risk factors: Renal failure DM with renal impairment Previous renal failure Dehydration Cardiovascular diseases Multiple contrast studies Multiple myeloma Nephrotoxic drugs Use of nonionic LOCM Similar to mx of renal failure from any cause, but usually self limiting 31
  32. 32. CM AND THE KIDNEY • More than 95% CM is excreted by the kidneys, 30% in first 1 hr ,75% in 6 hrs, totally from body within 2 days. • CM is excreted by glomerular filtration, easily filtered by glomerulous and not bound to protein. • Concentrated in the tubules about 100 times. • No tubular reabsorption. Choice of CM: Non ionic LOCM
  33. 33. CM induced renal failure – Rare but serious – Definition: Unexplained ↑creatinine level>25% or 44micmol/l within 3 days of contrast Mechanism: – ↓Renal blood flow – Direct toxic effect on tubules – Combines with Tamm-Horsfall/ Bence-Jones proteins Ultimately leading to Acute Renal Failure
  34. 34. Unpredictable reactions • Mechanism – Deactivation of ACE – Accumulation of bradykinin – Activation of complement system, kinins, coagulation and fibrinolytic system – Inhibition of cholinesterase vagal over stimulation Ach release collapse, bradycardia, bronchospasm 34
  35. 35. Classification of the severity of anphylactoid reactions Minor (1 in 20 cases) Moderate (1 in 200 cases) Severe (1 in 2000 cases) Nausea Limited vomiting Limited urtecaria Pruritus Sensation of heat, warmth or flushing Pallor and sweating Injection site pain Faintness, headache Severe vomiting Severe urticaria Angioedema (facial and laryngeal oedma0 Mild bronchospasm Dyspnoea, chest or abdominal – pain Hypotensive shock Pulmonary oedema Respiratory arrest Cardiac arrhythmia leading to cardiac arrest convulsions 35
  36. 36. Reaction and management • Minor rxn ;5% ( reassure,no need of treatment) • Intermediate rxn;1% (requires treatment but no need of hospitalization) extensive urticaria(H1+H2 blocker) bronchospasm;o2 inhalation inj.theophylline inj.Epinephrine sc/iv Laryngeal edema:O2 inhalation intubation if required inj.epinephrine Hypotension : elevate legs monitor pulse & manage accordingly • severe rxn-0.05% (requires intensive care) Anaphylactoid rxn,hypotension with tachycrdia(iv fluids,Inj.Epinephrine,Inj.hydrocort,o2 inhalation) vasovagal reactions(hypotension with bradycardia ,o2 inhalation,iv fluids,inj Atropine) 36
  37. 37. Incidence 37 CM reactions ICM NICM Incidence 3.8 – 12.7% 0.6 – 3.1% Mortality 1/30,418 1/207,488 High risk gp serious side effects 0.25% 0.045% Fatality rates 1/40,000 1/100.000-200,000 With prior reactions 18-20% 5-6% With premedication Lower lower
  38. 38. Specific recommended premedication Regimens • Elective premedication - prednisone 50 mg by mouth at 13 hrs,7 hrs, and 1 hr before CM injection plus Diphenhydramine -50 mg i.v , i.m or by mouth 1 hr before CM. -Methylprednisolone -32 mg by mouth 12 hr and 2 hr before CM injection. An anti-histamine can also be added to this regimen. If the patient is unable to take oral medication ,200 mg of hydrocortisone i.v may be substitued for oral prednisone in the Greenberger protocol. • Emergency premedication -Methylprednisolone sodium succinate 40 mg i.v every 4 hr until contrast study required. -Dexamethasone sodium sulfate 7.5 mg i.v - Omit steroids entirely and given diphenhydramine 50 mg i.v. NOTE; i.v steroids have not been shown to be effective when administered less than 4 to 6 hrs prior to contrast injection. 38
  39. 39. Golden rules concerning administration of contrast • CM should not be injected in an isolated clinical setting • The pt should never be left alone following injection, and i.v. access should be maintained throughout the examination until the potential for acute reactions has passed ~ 15 min • The person administering the contrast should have a basic medical history of the patient, particularly relating to previous allergic reactions and risk factors. • The wt of children should be known prior to the procedure. • Facilities for resuscitation should be available and equipment should be checked regularly. • The sites of resuscitation kit should be known to all persons working in dpt. • All personnel should have training in CPR and those dealing with children must be versed in paediatric resuscitation. 39
  40. 40. Emergency equipment for radiology department • O2 –piped or in a cylinder • Suction and catheter • Face mask • Airway • Laryngoscope • Ventilation bag • Needle and syringes • I.V giving set • Sthescope and sphygmomanometer • Emergency drugs (adrenaline ,atropine , dextrose 5% ,lignocaine etc) 40
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