1. Contrast media in radiology
Suppat ittimakin, MD.

2. Contrast media
Substance used to enhance the contrast of the structures or fluid within the body in medical imaging
Types of contrast agent
- Iodinated contrast agent
- MR contrast agent: Gadolinium-based contrast agent
- Negative contrast agent  air

3. Iodinated Contrast media
Radiopaque contrast agents are often used in radiography and fluoroscopy to help delineate borders between tissues with similar radiodensity
Types of iodinated contrast media
- Ionic
- Non-ionic

4. Effect of intravenous contrast injection

5. Contrast media Ionic contrast agents: Hyperosmolarity to blood
Should not be used for myelography or in injections that may enter the spinal canal (because neurotoxicity is a risk) or the bronchial tree (because pulmonary edema is a risk)
Incidence of irreversible renal failure in some medical condition such as paraproteinemia in multiple myeloma

6. Contrast media Nonionic contrast agents:
Low-osmolar (but still hyperosmolar relative to blood ; 300 mg I/ml) or iso-osmolar (with the same osmolarity as blood)
Now routinely used  Fewer adverse effects

9. MR contrast agent Extracellular contrast agent Organ specific agent
Blood pool agent

10. Gadolinum-based mr contrast
Improve visilbility of the internal body structures in MRI
Shortening of the T1 relaxing time of the atom
Do not pass blood brain barrier

12. Negative contrast media
Air: Use in double-contrast fluoroscopy

13. Contrast reaction

14. Goal of contrast usage
1) to assure that the administration of contrast is appropriate for the patient and the indication
2) to minimize the likelihood of a contrast reaction
3) to be fully prepared to treat a reaction should one occur

15. Adverse effect of intravenous contrast media
Allergy
Contrast-induced nephropathy
Nephrogenic systemic fibrosis
Contrast extravasation

16. Allergy

17. Risk factor for intravenous contrast reaction
Allergy
Asthma
Renal insufficiency
Cardiac status
Miscellaneous factors: Age, underlying disease such as hyperthyroidism, paraproteinemia in multiple myeloma, sickle cell anemia, etc.

18. Allergy
Allergic of prior contrast usage  increased 5 fold likelihood ratio
Allergic rhinitis ??
Seafood allergy ??
History of anaphylaxis

19. Asthma
A history of asthma may indicate an increased likelihood of a contrast reaction
Especially active hyperresponsive airway disease

20. Renal insufficiency
Can causes contrast-induced nephropathy (CIN), nephrogenic systemic fibrosis (NSF)
Metformin usage

21. Cardiac disease
Congestive heart disease, severe aortic stenosis, pulmonary hypertension, severe cardiomyopathy
May increased risk of contrast reaction
Attention should be paid to limiting the volume and osmolality of the contrast media.

22. Premedication
Approximately 90% of such adverse reactions are associated with direct release of histamine and other mediators from circulating basophils and eosinophils
Pathophysiologic explanations include activation of mast cells and basophils releasing histamine, activation of the contact and complement systems, conversion of L-arginine into nitric oxide, activation of the XII clotting system leading to production of bradykinin, and development of “pseudoantigens”

23. Premedication
Dose response studies in humans of the suppression of whole blood histamine and basophil counts by IV methylprednisone show a reduction in circulating basophils and eosinophils by the end of the first postinjection hour
However, reaching statistical significance compared with controls by the end of the second hour, and maximal statistical significance at the end of 4 hours

24. Recommended premedication regimens
Elective Premedication
Two frequently used regimens are:
First regimen:
Prednisone – 50 mg by mouth at 13 hours, 7 hours, and 1 hour before contrast media injection, plus
Diphenhydramine (Benadryl®) – 50 mg intravenously, intramuscularly, or by mouth 1 hour before contrast medium

25. Recommended premedication regimens
Second regimen:
Methylprednisolone (Medrol®) – 32 mg by mouth 12 hours and 2 hours before contrast media injection
An anti-histamine (as in option 1) can also be added to this regimen injection
If the patient is unable to take oral medication, 200 mg of hydrocortisone intravenously may be substituted for oral prednisone

26. Recommended premedication regimens
Emergency Premedication (In Decreasing Order of Desirability)
Methylprednisolone sodium succinate (Solu-Medrol®) 40 mg or hydrocortisone sodium succinate (Solu-Cortef®) 200 mg intravenously every 4 hours (q4h) until contrast study required plus diphenhydramine 50 mg IV 1 hour prior to contrast injection

27. Recommended premedication regimens
Dexamethasone sodium sulfate (Decadron®) 7.5 mg or betamethasone 6.0 mg intravenously q4h until contrast study must be done in patent with known allergy to methylpred-nisolone, aspirin, or non-steroidal anti-inflammatory drugs, especially if asthmatic. Also diphenhydramine 50 mg IV 1 hour prior to contrast injection.
Note: IV steroids have not been shown to be effective when administered less than 4 to 6 hours prior to contrast injection.

28. premedication
Type of contrast agent
Osmolarity: Hyperosmolality is associated with the stimulation of release of histamine from basophils and mast cells
Complexity and molecular size: Increase in the size and complexity of the contrast molecule may potentiate the release of histamine
Nonionic monomers also produce lower levels of histamine release from basophils compared with high-osmolality ionic monomers, low-osmolality ionic dimers and iso-osmolality nonionic dimers

29. ACUTE CONTRAST REACTION
Allergic-liked reaction : from histamine which is released by mast cell and basophil
Physiologic reaction : direct chemotoxicity, osmotoxicity (adverse effects due to hyperosmolality) or molecular binding to certain activators
Frequently dose and concentration dependent
Frequent reaction: vagovagal reaction, feeling of apprehension and accompanying diaphoresis
Rare reaction: Cardiac arrhythmias, depressed myocardial contractility, cardiogenic pulmonary edema, and seizures

30. Delayed contrast reaction
Most commonly cutaneous and may develop from 30 to 60 minutes to up to one week following contrast material exposure
Can occurring between three hours and two days
Symptoms; allergic-liked cutaneous reaction (most common), nausea/vomitting, fever, headache, iodine-related sialoadenopathy, polyarthroplasty

31. Evaluation of the contrast reaction
Mild reaction
Signs and symptoms are self-limited without evidence of progression. Mild reactions include:
Allergic-like : Limited urticaria / pruritis Limited cutaneous edema Limited “itchy” / “scratchy” throat Nasal congestion/ Sneezing / conjunctivitis / rhinorrhea
Physiologic : Limited nausea / vomiting/ Transient ushing / warmth / chills Headache / dizziness / anxiety / altered taste Mild hypertension/ Vasovagal reaction that resolves spontaneously

32. Evaluation of the contrast reaction
Moderate
Signs and symptoms are more pronounced and commonly require medical management. Some of these reactions have the potential to become severe if not treated. Moderate reactions include:
Allergic-like
Diffuse use urticaria / pruritis, Diffuse erythema, stable vital signs, Facial edema without dyspnea, Throat tightness or hoarseness without dyspnea
Wheezing / bronchospasm, mild or no hypoxia

33. Evaluation of the contrast reaction
Moderate
Physiologic
Protracted nausea / vomiting Hypertensive urgency Isolated chest pain
Vasovagal reaction that requires and is responsive to treatment

34. Evaluation of the contrast reaction
Severe
Allergic-like
Diffuse edema, or facial edema with dyspnea Diffuse erythema with hypotension Laryngeal edema with stridor and/or hypoxia, Wheezing / bronchospasm, Significant hypoxia, Anaphylactic shock (hypotension + tachycardia)
Physiologic
Vasovagal reaction resistant to treatment Arrhythmia Convulsions, seizures Hypertensive emergency

35. Treatment of Mild reaction
Typically do not require medical treatment
Vital signs should be obtained to detect hypotension that may be clinically silent while the patient is supine
Observed for 20 to 30 minutes, or as long as necessary
Antihistamine IV

36. Treatment of Moderate to severe reaction
IV fluid
Antihistamine : Benadryl 1 mg/kg IV for moderate urticaria
Epinephrine 0.1 mg/kg IV or 0.3 mg IM for profound hypotension, anaphylaxis, bronchospasm
Betaagonist inhalator for mild and moderate bronchospasm

37. Contrast-induced nephropathy (cin)

38. Contrast-induced nephropathy
A sudden deterioration in renal function that is caused by the intravascular administration of iodinated contrast medium
Diagnosis by use percent change in the baseline serum creatinine and absolute elevation from baseline serum creatinine (absolute increase of 0.5 mg/dL over a baseline)

39. Definition of acute renal injury
The diagnosis of AKI is made according to the AKIN criteria if one of the following occurs within 48 hours after a nephrotoxic event (e.g., intravascular iodinated contrast medium exposure):
Absolute serum creatinine increase ≥0.3 mg/dL (>26.4 μmol/L)
A percentage increase in serum creatinine ≥50% (≥1.5-fold above baseline)
Urine output reduced to ≤0.5 mL/kg/hour for at least 6 hours.

40. eGFR is gaining attention as a potentially better marker of CIN risk
Renal function
Serum creatinine concentration is the most commonly used measure of renal function
BUT!!! Serum creatinine has limited accuracy for evaluate GFR
Calculated estimated glomerular filtration rate (eGFR) is more accurate than is serum creatinine at predicting true GFR
eGFR is gaining attention as a potentially better marker of CIN risk

41. Risk factors
Pre-existing severe renal insufficiency  Most important risk factor
- eGFR < 30 ml/min/1.73 m2  significant risk
Underlying disease: DM, Cardiovascular disease, Multiple myeloma, Hypertension
Dehydration
Diuretic use
Advanced age
Multiple iodinated contrast medium doses in a short time interval (<24 hours)

42. Prevention Avoid usage of the iodinated-contrast agent
Select type of contrast agent : LOCM are less nephrotoxic than HOCM in patients with underlying renal insufficiency.
Volume expansion : Major effective action
- 0.9% saline at 100 mL/hr, beginning 6 to 12 hours before and continuing 4 to 12 hours after intravenous iodinated contrast administration
N-acetylcysteine : unknown mechanism

43. Renal insufficiency
Most low-osmolality iodinated contrast media are not protein-bound, have relatively low molecular weights, and are readily cleared by dialysis
Unless an unusually large volume of contrast medium is administered, or there is substantial underlying cardiac dysfunction, there is no need for urgent dialysis after intravascular iodinated contrast medium administration

44. Nephrogenic systemic fibrosis (NSF)

45. Nephrogenic systemic fibrosis
Fibrosing disease, primarily involving the skin and subcutaneous tissues
but also involve other organs, such as the lungs, esophagus, heart, and skeletal muscles
Initial symptoms typically include skin thickening and/or pruritis
May develop and progress rapidly, with some affected patients developing contractures and joint immobility
In some patients, the disease may be fatal

46. Association
Gadolinium-based MR contrast
Acute kidney injury (AKI)
Chronic renal disease
Patients with end-stage CKD (CKD5, eGFR < 15 mL / min/1.73 m2) and severe CKD (CKD4, eGFR 15 to 29 mL / min/1.73 m2) have a 1% to 7% chance of developing NSF after one or more exposures to at least some GBCAs

47. Recommendation
ACR Committee on Drugs and Contrast Media believes that patients receiving any GBCA should be considered at risk of developing NSF if any of the following conditions applies:
on dialysis (of any form)
severe or end-stage CKD (CKD 4 or 5, eGFR < 30 mL / min/1.73 m2) without dialysis
eGFR 30 to 40 mL / min/1.73 m2 without dialysis*
AKI

48. NSF with hemodialysis Hemodialysis ???
Most patients who developed NSF had end-stage kidney disease and were on dialysis at the time of exposure
So, hemodialysis cannot prevent NSF !!!

49. Contrast extravasation

50. Contrast extravasation
Leakage of the contrast agent from systemic circulation
Incidence 0.1% - 0.9%
Sign and symptom:
Complain of initial swelling or tightness, and/or stinging or burning pain at the site of extravasation
Edematous, erythematous, and tender nearby the injected site

53. risk of contrast extravasation
Patients who cannot communicate adequately
Severely ill or debilitated patients
Patients with abnormal circulation in the limb to be injected :
- Atherosclerotic peripheral vascular disease
- Diabetic vascular disease, Raynaud’s disease, venous thrombosis or insuffciency
- Prior radiation therapy or extensive surgery

54. risk of contrast extravasation (cont.)
>24 hour of injected site
Multiple venous punture
High injected flow rate ???
Amount of injected contrast agent ???

55. Sequelae of contrast extravasation
Acute local inflammatory response (24-48 hr)  due to hyperosmolarity of the contrast media
Hyperosmolar contrast agent can cause more severe reaction than low-osmolar contrast agent
Most extravasations are limited to the immediately adjacent soft tissues (typically the skin and subcutaneous tissues), and usually there is no permanent injury

56. Complication of the contrast extravastion
Compartment syndrome  occur after large amount of contrast leakage
Skin ulceration
Soft tissue necrosis

58. Treatment of contrast extravasation
Elevation of the affected extremity above the level of the heart  decrease capillary hydrostatic pressure and promote resorption of extravasated fluid
Warm or cold compresses ???
Aspirate the extravasated contrast medium through an inserted needle or angiocatheter ???
Local injection of other agents such as corticosteroids or hyaluronidase ???
Surgical consult : progressive swelling or pain, altered tissue perfusion, change in sensation in the affected limb, and skin ulceration or blistering

59. References
Introduction ACR Manual on Contrast Media – Version 10.1, 2015

60. Thank you for your ATTENTION