About iodinated contrast

1. Radiographic
Contrast Media I
1
Presenter: Seema Dixit
Bsc MIT 2015
BPKIHS

2. Contents
• Introduction
• Historical development
• Basic chemistry
• Classification
• Risk factor
• Adverse rxn and management
• Premedication
• Golden rules
• Emergency equipment 2

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
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4. 4

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.
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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
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COOH
NHCOCH3
I
I
I

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.
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•This compound sodium diatrizoate (Urograffin) was introduced
for clinical use.
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COOH
NHCOCH3
I
I
I
CH3CONH

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.
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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
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. 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. 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
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14. HOCM: Chemical Structure
• These are salts consisting of ->
– Tri-iodinated benzoic acid anion with
– Na+ or Methylglucamine (meglumine) cation.
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RR
II
I
COO-- Na/Meg+
Monomeric and Monoacid
Eg: Ionic Monomers
Iothalmate
Diatrizoate
Iodine particle ratio 3:2

15. Diatrizoate
• INCRESAES Solubility
• Decreases plasma
protein binding
there by increaseing
its ability to be
filtered in glomerulus
• Improves patient
tolerence
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NHCOCH3
II
I
COO--
NHCOCH3
Eg: Urograffin, Angiogrffin, Trazogrff, Urovision,Urovideo
Na/Meg+

16. Iothalmate
• Better neural
tolerance
• Decreased CVS
tolerence
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COOHR
II
I
COO-- Na/Meg+
Eg: Conray, Triovideo.

17. Ioxaglic acid: Hexabrix
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R
II
I
COO--
R
II
I
R
R
Na+
Meg-
Dimeric -monoacid IP ratio 6:2

18. Non-ionic Monomers
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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. Non-ionic Dimers
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ROH
II
I
ROH
HOR
II
I
ROH
R
IP ratio 6:1
Dimeric-non-ionic
Eg: Iodixanol

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.
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21. Iodinated Contrast Media
• Ionic
• Nonionic

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. 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. 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.
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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
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26. Predictable reactions
• Affects specific organs and systems
– Soft tissues
– Cardiovascular
• Venous
• Arterial
• Cardiac
– Renal
– CNS
– Hematological
– Endocrine
• thyroid
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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
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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
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29. Chemo toxic reactions on Cardiovascular
system-Arterial sys
Effect Prophylaxis Management
Pain, heat d/t
vasodilatation
Endothelial
damage
Use of LOCM Conservative
Reassurance
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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
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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
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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. 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. 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
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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
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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. Incidence
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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. 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.
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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.
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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)
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