This document discusses contrast-induced nephropathy (CIN), an important cause of hospital-acquired acute kidney injury. It defines CIN and outlines its risk factors such as pre-existing kidney disease, diabetes, procedures using high volumes of contrast, and certain medications. The mechanisms of CIN and its natural history are described. Prevention strategies like adequate hydration and use of low-osmolar contrast agents are recommended. The role of N-acetylcysteine in prevention is controversial based on conflicting trial results. The overall incidence of CIN in one study was reported as 12.6%.

2. PRESENTED BY
Dr Sameer Peer
MODERATOR
Dr Naseer A Choh(MD)
Associate Professor
SENIOR RESIDENT i/c
Dr Azhar Khan(MD)
Senior Resident

3. INTRODUCTION
• Various forms of contrast media have been used to improve medical imaging.
• Their value has long been recognized, as attested to by their common daily use
in imaging departments worldwide.
• Like all other pharmaceuticals, however, these agents are not completely devoid
of risk.
• Adverse side effects from the administration of contrast media vary from minor
physiological disturbances to rare severe life-threatening situations.
• Preparation for prompt treatment of contrast media reactions must include
preparation for the entire spectrum of potential adverse events and include
prearranged response planning with availability of appropriately trained
personnel, equipment, and medications.
• Thorough familiarity with the presentation and emergency treatment of
contrast media reactions must be part of the environment in which all
intravascular contrast media are administered.

4. As would be appropriate with any diagnostic procedure, preliminary considerations for the
referring physician and the radiologist include:
1. Assessment of patient risk versus potential benefit of the contrast assisted examination.
2. Imaging alternatives that would provide the same or better diagnostic information.
3. Assurance of a valid clinical indication for each contrast medium administration.
Because of the documented low incidence of adverse events, intravenous injection of
contrast media may be exempted from the need for informed consent, but this decision
should be based on state law, institutional policy, and departmental policy.

5. The approach to patients about to undergo a contrast-enhanced examination has three
general goals:
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; and
3) to be fully prepared to treat a reaction should one occur
Achieving these aims depends on :
• obtaining an appropriate and adequate history for each patient,
• preparing the patient appropriately for the examination,
• having equipment available to treat reactions, and
• ensuring that expertise sufficient to treat even the most severe reactions is readily at
hand.
Although mild reactions to contrast media are relatively common, they are almost invariably
self-limited and of no consequence.
Severe, life threatening reactions, although rare, can occur in the absence of any specific
risk factors with any type of media.

6. RISK FACTORS FOR ADVERSE REACTIONS
• Previous contrast reaction
• Type of contrast agent
• Allergy
• Asthma
• Renal insufficiency
• Cardiovascular disease
• Diabetes
• Anxiety
• Multiple myeloma
• Beta-blockers
• Sickle cell disease
• Age
• Concomitant use of intra-arterial medications like papavarine
• Pheochromocytoma
• Hyperthyroidism
• Myasthenia Gravis

7. Types of adverse reactions
IDIOSYNCRATIC NONIDIOSYNCRATIC
UNRELATED CHEMOTOXIC RELATED OSMOLARITY
RELATED

8. IDIOSYNCRATIC REACTIONS
Definition : unpredictable reactions which occur within 1 hour of contrast medium
administration and which are unrelated to the dose of the contrast medium above a
certain level.
• Serious and most dreaded
• Occur without warning
• Cannot be reliably predicted
• Are not preventable in the present state of our knowledge
Mechanism :
• Anaphylactoid reactions
• There is no evidence to suggest a true antigen-antibody reaction
• These involve bradykinin,histamine,leukotrienes, prostagalndins and complement
factors
• Proposed mechanisms include :
 Enzyme inhibition : cholinesterase inhibition
 Vasoactive substances
 Cascade systems : Complement, Coagulation, Kinin, fibrinolysis
 Immune disturbances
 Anxiety, apprehension and fear

9. Risk reduction techniques
• Obtaining Clinical information – history of previous reaction is the most important risk
factor to consider.
• Alternative Diagnostic test
• If still necessary , then risk may be reduced by :
 Choice of contrast media : non-ionic LOCM have 4-5 times lower risk
 Premedication : Elective or Emergency
Elective
• Prednisone 50 mg PO @
13,7 and1h prior
• Diphenhydramine – 50
mg IV/IM/PO 1h before
• If patient cannot take oral
medication,
Hydrocortisone 200 mg IV
may be substituted for
prednisone
Emergency
• Hydrocortisone 200 mg IV
every 4 hours till the study
• Diphenhydramine 50 mg
IV 1 hour prior
• No use of steroids if given
less than 4-6 hrs before
• Diphenhydramine 50 mg
IV (without steroids) in
very urgent scans.

10. TYPES AND MANAGEMENT OF ACUTE IDIOSYNCRATIC REACTIONS
Mild
• Nausea, mild
vomiting, mild
urticaria, itching
• Observation,
monitoring of vitals,
reassurance
• Antihistaminics as
and when required
Moderate
• Urticaria, Facial or
laryngeal edema,
bronchospasm
• Close monitoring
until symptoms
resolve
• Treatment specific
for the type
Severe
• Hypotension with
tachycardia
• Hypotension with
bradycardia
• Severe hypertension
• Seizures
• Pulmonary edema

11. A – Airway
B – Breathing
C – Circulation
D – Disability
E – Exposure
Call for help immediately while
resuscitating – do not hesitate
INITIAL APPROACH – ABCDE of Critical care

12. Management of moderate reactions
1. URTICARIA
• Discontinue the injection if not
completed
• No Rx in most cases
• H1-receptor blocker:
Diphenhydramine IV/IM/PO 25-50
mg
• Severe or widely disseminated
urticaria –Adrenaline (1:1000) 0.1-
0.3 ml SC (if no contraindications)

13. 2. Facial or laryngeal edema
• Oxygen @6-10 L/min (by
mask)
• Adrenaline SC or IM 0.1-
0.3 ml of 1:1000
• If Hypotension is present
– Adrenaline 3 ml of
1:10000 IV preferably
under ECG monitoring
• If not responsive – can be
repeated upto 1 mg
• Always seek appropriate
assisstance in non-
responsive cases

14. 3. Bronchospasm
• Oxygen 6-10L/min (mask)
• ECG, Saturation, BP
• Beta-agonist inhalers
(bronchodilators : terbutaline,
albuterol, metaproterenol) 2-3 puffs:
repeat as necessary
• IV/IM/SC adrenaline if not
responding
• IM/SC : 0.1-0.3 ml (1:1000)
• If hypotension – IV slow 1-3 ml (
1:10000) under ECG monitoring
• Max dose upto 1 mg
• Assistance must be sought in case of
non-responders and if SPO2 <88%

15. Management of Severe Reactions
1. Hypotension with tachycardia
• Legs elevated or Trendelenberg position
• ECG, Saturation, BP
• Oxygen @6-10 L/min (mask)
• Rapid IV fluids [ Ringer Lactate/NS)
• If poorly responsive, IV Adrenaline
1:10000 1 ml upto max 1 mg dose
• Appropriate assisstance must be sought
2. Hypotension with Bradycardia (Vagal
reaction)
• Secure airway. Oxygen 6-10 L/min
• Monitor vitals
• Raise Legs >60 deg or Trendelenberg
position
• IV fluids : Ringer lactate/NS
• Atropine 0.6-1 mg IV slow , max dose
upto 0.04mg/kg (2-3 mg) in adult
• Complete resolution of bradycardia and
hypotension before discharge

16. 3. Hypertension (severe)
• Oxygen @ 6-10 L/min (mask)
• Monitor ECG, Saturation, BP
• Nitroglycerine 0.4 mg Tab, Sublingual ( may repeat x 3 times) or, topical 2%
ointment, apply 1-inch strip
• If not responsive, then Labetalol 20 mg IV stat, F/B 20-80 mg IV every 10 minutes
upto a maximum of 300 mg.
• Shift to ICU or emergency medicine department
• For Pheochromocytoma – Phentolamine 5 mg IV . ( may use Labetolol if
Phentolamine is not available)
4. Seizures
• Oxygen @ 6-10 ml/min (mask)
• Diazepam 5 mg IV ( or more as appropriate) or midazolam 0.5 – 1 mg IV
• Phenytoin 15-18 mg/kg @ 50 mg/min for longer effect – after physician
consultation.
• Benzodiazepines may cause respiratory depression – close monitoring of vitals is
necessary
• Appropriate assistance must be sought

17. 5. Pulmonary edema
• Oxygen @ 6-10 ml/min (mask)
• Elevate torso
• IV diuretic – furosemide 20-40 mg IV slow
• Consider morphine (1-3 mg IV).
• Shift to ICU or Emergency medicine
department

18. Non-Idiosyncratic reactions
Definition : These are dose related reactions and depend upon the physio-
chemical properties of the contrast medium, i.e. chemical composiion,
Osmolality and concentration of the injected contrast and also on the volume,
speed and multiplicity of the injection.
Reactions unrelated to contrast media :
• Pyrogenic
• Vasovagal
• Excessive dehydration
• Hypertensive crisis in pheochromocytoma
• Hypoglycemia
Chemotoxic
• Cardiovascular
• Neurologic
• Renal

19. Hyperosmolar reactions : Due to very high osmolarity of HOCMs –
erythrocyte damage, BBB damage, endothelial damage, vaodalitation,
hypervolemia and cardiac depression.

20. CONTRAST EXTRAVASATION
• It refers to the escape of the contrast material from the vessel in which it is
introduced, into the surrounding tissue or body cavity
• 0.1-0.9% of contrast injections
• Risk factors : Atherosclerosis, PVD, Diabetes, Raynaud’s disease, Venous
thrombosis, prior radiation, extensive surgery, severely ill and deblitated,
indwelling lines > 24 hrs, multiple injections in onto same vein.
• Clinical features : Mild – edema, erythema, stinging, tenderness
Severe – Compartment syndrome, ulcers, necrosis
• Prevention is better than cure – ensure properly secured IV access, extravasation
detectors
• Treatment – depends on the volume of extravasation

21. < 20 mL
- Elevate the arm and
observe
20-100 mL
- Aspirate
- Intermittent Ice
- Hyaluronidase (50-
250 U) locally
> 100 mL
- Aspirate
- Intermittent Ice
- Hyaluronidase (50-
250 U) locally
- In case of
pallor/pulselessness/
worsening
pain/parasthesias/skin
changes – Plastic
surgery consultation
Management of Contrast extravasation

22. CONTRAST-INDUCED NEPHROPATHY
• Contrast induced nephropathy (CIN) is a common cause of hospital acquired acute kidney
injury and is recognised as the third most common cause of hospital acquired acute
kidney injury (AKI) after impaired renal perfusion and nephrotoxic medications.
• CIN accounts for 11-12% of all cases of in-hospital AKI and is associated with an in-
hospital mortality rate of 6%.
• The incidence of CIN is expected to increase in future because of the escalating use of
iodinated contrast agents, ageing population, increasing incidence of chronic kidney
disease (CKD) and diabetes.
• Among all the diagnostic or therapeutic procedures utilising iodinated contrast media,
the risk of development of CIN is highest with coronary angiography and PCI.
• The overall incidence of CIN after coronary interventions is about 14.5% with in-hospital
mortality rate of 7.1% in patients without undergoing dialysis and 35.7% in those
requiring dialysis

23. Definition and diagnosis of CIN
• CIN is defined as an acute deterioration of renal function after parenteral exposure to
contrast media in absence of other causes.
• The levels of serum creatinine (Scr) begin to rise within 24-48 hours and peak at 2-3 days
and return to the baseline values within 2 weeks.
• There is no specific standard definition of CIN that is agreed upon or utilized in the
literature.
• The most common definition of CIN is either a relative increase in serum creatinine from
baseline value of 25% or an absolute increase of 0.5 mg/dL within 48 to 72 hours after
contrast exposure.
• Additionally, the creatinine elevation must not be attributable to other causes and must
persist for 2 to 5 days.
• A 5% increase in the serum creatinine levels at 12 hours after exposure to contrast media
has been shown to be highly predictive of CIN.

24. MECHANISM OF CIN

25. Patient-related risk factors
Pre-existing kidney disease
Diabetes with chronic kidney disease
Age > 75 y
Dehydration a
Hypoalbuminemia (<35 g/L) a
Poor heart function or hemodynamic instability a
Pre-procedure intra-aortic balloon pump
Anemia or post-procedure drop in hematocrit
Hypotension
Advanced heart failure
Left ventricular ejection fracture <40%
Acute myocardial infarction or increased CK-MB
Need for cardiac surgery after contrast exposure
Urgent or emergent procedure
Peripheral vascular disease
Concurrent nephrotoxic medication a
: NSAIDs,
aminoglycoside, amphotericin B, high dose
diuretics,antiviral drugs such as acyclovir and
foscarnet, cyclosporine A
Procedure related factors
Type of Contrast medium a
High osmolar Contrast medium
Ionic v/s non-ionic Contrast medium
High viscosity Contrast medium
High Volume Contrast medium a
Multiple contrast medium injections
within 72 ha
Intra-arterial v/s intra-venous
New risk factors a
Metabolic syndrome
Pre-diabetes
Hyperuricemia
Conflicting risk factors
Female
Multiple Myeloma
Cirrhosis
ACEI or ARBs
Diabetes with normal renal function
Renal transplant
LOCMs in high risk patients
RISK FACTORS FOR CIN

26. Natural History and prognosis of CIN
Most cases of CIN are self-limited. Serum creatinine levels typically increase over 1-3
days, peak at 4-5 days and then return to baseline in about 2 weeks.
In more severe cases, serum creatinine levels may show a delayed peak and a slow
return to a steady state which is above the baseline.
Such cases may develop oliguria. In a small number of cases, temporary or permanent
dialysis may be required.
Among those who require dialysis, median 2-year survival is 19% and in-hospital
mortality may be as high as 36%.

27. PREVENTION OF CIN
• Avoidance of iodinated contrast
• Contrast media selection : HOCM/IOCM/LOCM
• Hydration : Single most effective way of prevention – but should be adequate
Inpatient
0.9% NS 1 cc/kg/h for 12 hours pre, 1 cc/kg/h for 12 hours post
Outpatient/emergent
0.9% NS 2 cc/kg/h for 2–3 hours pre, 1 cc/kg/h for 6 hours post
0.9% NS or Na Bicarb (154 mEq/L): 3 cc/kg/h for 1 hour pre, 1 cc/kg/h for 6 hours
post
NS, normal saline; Na Bicarb, sodium bicarbonate

28. The role of N-acetylcysteine in prevention of CIN is controversial.
In 2000, Tepel et al reported the first human trial for NAC in the prevention of CIN.
Marenzi et al demonstrated a dose-dependent protective effect of NAC.
However, many trials evaluating NAC for the prevention of CIN have yielded conflicting
results.
The largest meta-analysis found that either oral or IV NAC could significantly lower the
risk of CIN when compared with NS hydration.
Other agents – diuretics, theophylline, fenoldopam, endothelin-1 etc – theoretic benefit
only, not recommended for use.
N-acetyl Cysteine

30. The overall incidence of contrast induced nephropathy in our study population was 12.6%.
We evaluated the various risk factors associated with CIN.
We found that advanced age, BMI, route of administration, type of procedure, nature of
contrast material, volume of contrast material, hypertension, diabetes mellitus, pre-existing
renal insufficiency, hypotension, concomitant nephrotoxic medication, hospitalization, heart
failure, coronary artery disease and eGFR<60 ml/min/1.73 m2 were significant risk factors
for CIN.
Multivariate logistic regression revealed that among these risk factors, heart failure, pre-
procedure serum creatinine level of ≥ 1.5 mg/dl and nature of contrast material used for the
procedure were independent risk factors for CIN.
In order to determine whether contrast exposure actually causes renal impairment or it
could be explained by variations of serum creatinine levels in absence of contrast exposure,
we compared the contrast group with a control group of patients who were comparable to
contrast group with respect to the other risk factors.
We found a significant difference in the variations of serum creatinine levels between the
two groups.
We found that CIN is associated with a greater risk for renal replacement therapy and in-
hospital mortality.

31. We also found that prophylactic measures did not result in reduction of risk of CIN among
high-risk group and also among those with pre-procedure serum creatinine levels of ≥1.5
mg/dl.

32. Risk factor CIN (n=28) No CIN (n=194) p value
Mean Age (years) 59.46±11.33 47.44±16.87 0.0003
Female Sex 12(42.85%) 86(44.32%) 0.88
Mean BMI (kg/m2
) 26.09±3.61 24.57±3.76 0.04
Procedure
 IVU (n=69)
 CECT (n=107)
 PCI (n=46)
0(0%)
13(12.14%)
15(32.6%)
69(100%)
94(87.86%)
31(67.4%)
<0.0001
Route
 IA (n=46)
 IV (n=176)
15(32.6%)
13(7.38%)
31(69.4%)
163(92.62%)
<0.0001
Nature of contrast agent
 LOCM (n=213)
 IOCM (n=9)
23(10.79%)
5(55.55%)
190(89.20%)
4(44.45%)
<0.0001
Mean volume of contrast agent (ml) 115.71±45.31 76.15±32.18 <0.0001
Hypertension 22(78.57%) 45(23.19%) <0.0001
Diabetes mellitus 21(75%) 58(29.89%) <0.0001
Malignancy 7(25%) 57(29.38%) 0.62
Chemotherapy 6(21.42%) 27(13.91%) 0.317
Hypotension 9(32.14%) 7(3.60%) <0.0001
Heart failure 14(50%) 6(3.09%) <0.0001
Nephrotoxic medications 11(39.28%) 14(7.21%) <0.0001
Pre-procedure SCr (mg/dl) 1.32±0.33 0.91±0.24 <0.0001
Pre-procedure SCr≥1.5 mg/dl 11(39.28%) 5(2.57%) <0.0001
Diabetics with Pre-procedural SCr
≥1.5 mg/dl
8(28.57%) 3(1.54%) <0.0001
Post-procedure SCr (mg/dl) 2.53±1.74 0.98±0.28 <0.0001
Coronary artery disease 19(67.85%) 30(15.46%) <0.0001
Peripheral arterial disease 3(1.07%) 7(3.60%) 0.13
Multiple myeloma 1(3.57%) 2(1.03%) 0.34
Metformin 4(14.28%) 17(8.76%) 0.37
Inpatients 21(75%) 56(28.86%) <0.0001

33. CIN NO CIN p value
HIGH-RISK (n=53)
 NS
 NAC
 Bicarbonate
13(68.42%)
9(47.36%)
7(36.84%)
22(64.70%)
6(17.64%)
6(17.64%)
0.78
0.02
0.12
RENAL INSUFFICIENCY (n=16)
 NS
 NAC
 Bicarbonate
9(81.81%)
9(81.81%)
8(72.72%)
5(100%)
5(100%)
3(60%)
0.32
0.32
0.62

34. Variable Contrast Group(n=222) Control Group(n=148) p value
Age (Mean years) 48.97±16.74 47.48±17.21 0.4106
Males (%) 55.85 55.40 0.9321
BMI (Mean kg/m2
) 24.76±3.76 24.29±3.02 0.2044
Diabetes (%) 35.58 34.45 0.8237
Hypertension (%) 30.18 33.78 0.4663
Malignancy (%) 28.82 25.00 0.4197
Chemotherapy (%) 14.86 11.48 0.3521
Metformin (%) 9.45 8.78 0.8272
Hypotension (%) 7.2 4.05 0.2098
Scr ≥1.5 mg/dl 7.2 6.75 0.8683
Nephrotoxic drugs (%) 11.26 9.45 0.5790
Previous exposure (%) 3.15 3.37 0.9069
CAD (%) 22.07 17.5 0.2805
PAD (%) 4.5 2.7 0.3744
Multiple Myeloma (%) 1.35 3.3 0.2037
Heart Failure (%) 9.09 8.1 0.7409
High-risk (%) 23.87 22.29 0.7248
Day 0 Scr (control)/ Pre-Scr
(contrast)
0.96±0.29 0.90±0.35 0.0738
Day 4 Scr (control)/Post-
Scr (contrast)
1.17±0.84 0.96±0.41 0.0050
Inpatients (%) 34.68 34.45 0.9637
Comparison between contrast and control groups

35. Variable Coefficient p-value
Heart failure 4.25 0.001
Pre-procedure Scr ≥1.5 3.99 0.005
Nature of contrast material ─1.41 0.001

36. The logistic regression equation for this model was obtained as follows:
Y = ∑βx
Where,
Y represents occurrence of CIN, β represents coefficient of the variable, x represents the
variable.
Thus,
Y = 4.25(Heart failure) + (─1.41)(Nature of contrast material) + 3.99(Pre-procedure Scr≥1.5)
Values for different variables to be entered in the equation are:
Heart failure – 0 (if not present) or 1(if present)
Nature of contrast material – 0(iopamidol), 1(iomeprol), 2(iohexol) and 3(iodixanol)
Pre-procedure Scr≥1.5 – 0(if not present) or 1(if present)
The probability of occurrence of CIN based on this model can be calculated as:
P = eY/1+eY
Where,
P represents the probability of occurrence of CIN, e is the exponent with value of 2.71828 and
Y is the value obtained from the logistic regression equation.

37. The prediction of CIN using our model can be illustrated in the form of an example.
Considering a hypothetical situation where a given patient has pre-procedure Scr of
1.2 mg/dl (to be entered in the equation as 0), he is in heart failure (to be entered
in the equation as 1) and iohexol is used as the contrast agent (to be entered in the
equation as 2), then,
Y = 4.25(1) ─ 1.41(2) + 3.99(0)
Solving for Y,
Y = 1.43
Therefore, the probability of occurrence of CIN in this case according to our model
is:
P = e1.43/e1.43 +1 = 80.65%

38. Nephrogenic systemic fibrosis
Definition
Nephrogenic systemic fibrosis (NSF) is a fibrosing disease, primarily involving the skin and
subcutaneous tissues but also known to involve other organs, such as the lungs,
esophagus, heart, and skeletal muscles.
Initial symptoms typically include skin thickening and/or pruritis.
Symptoms and signs may develop and progress rapidly, with some affected patients
developing contractures and joint immobility. In some patients, the disease may be fatal.

39. Associations
Gadolinium-based contrast agent (GBCA) administration
When first described in 2000, NSF was noted to occur predominantly in patients with
end-stage chronic kidney disease (CKD), particularly in patients on dialysis.
In 2006 several groups noted a strong association between gadolinium-based contrast
agent (GBCA) administration in patients with advanced renal disease and the
development of NSF, and it is now generally accepted that GBCA exposure is a necessary
factor in the development of NSF.
The time between injection of GBCA and the onset of NSF symptoms occurs within days
to months in the vast majority of patients; however, in rare cases, symptoms have
appeared years after the last reported exposure.

40. The development of NSF is related to the release of gadolinium from the chelates that
constitute GBCAs – the differences in number of reported cases may, in part, be explained
by differences in chemical properties of different GBCAs.
However, a combination of other factors, including market share, number of years that
the agent has been in use, and possible reporting bias, also may contribute to differences
in number of reported cases associated with the various GBCAs.

41. Chronic kidney disease
• Based upon current knowledge, it is estimated that 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.
• However, most patients who developed NSF had end-stage kidney disease and were on
dialysis at the time of exposure. Moreover, among patients with severe CKD (CKD4) that
developed NSF (approximately 3% of all reported NSF cases), most had an eGFR closer to
15 ml/min/1.73 m2 than to 30 ml/min/1.73 m2.
• There has been only one published case report of a patient with eGFR values above 30
ml/min/1.73 m2.
Acute kidney injury (AKI)
• Between 12% and 20% of confirmed cases of NSF have occurred in patients with AKI,
often superimposed upon CKD.
• Some cases of NSF have developed in patients with AKI without underlying CKD.
• AKI alone is also a risk factor for NSF development in the consensus opinion of the ACR
Committee on Drugs and Contrast Media.

42. Others – high dose, multiple doses, Elevated serum calcium/phosphate/iron levels,
metabolic acidosis, high-dose erythropoietin therapy, imunosuppression, hepato-renal
syndrome
Postulated Mechanism
• The exact mechanism of NSF causation is unknown.
• The most widely held hypothesis is that gadolinium ions dissociate from the chelates
in GBCAs in patients with significantly degraded renal function due to the prolonged
clearance times of the GBCAs, as well as to other metabolic factors associated with
this level of renal disease.
• The free gadolinium then binds with an anion such as phosphate, and the resulting
insoluble precipitate is deposited in various tissues.
• A fibrotic reaction ensues, involving the activation of circulating fibrocytes.

43. Patients at Risk for NSF
• 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
Patients with eGFR 30 to 40 ml/min/1.73 m2 should also be considered at risk because
eGFR levels may fluctuate
(e.g., from the 30 to 40 ml/min/1.73 m2 range one day to below < 30 ml/min/1.73 m2
on another day).

44. For Inpatients : eGFR should be obtained 2 days prior to GBCA administration

45. General Recommendations for Imaging Patients at Risk for NSF
• Once a patient at risk for NSF is identified, alternative diagnostic examinations that do not
employ a GBCA should be considered.
• In nonemergent or nonurgent cases if the potential benefits of a GBCA-enhanced MRI are
felt to outweigh the risk of NSF in an individual patient and there is no suitable alternative,
the referring physician and patient should be informed of the risks of GBCA administration,
and both should agree with the decision to proceed.
• In emergent or urgent cases it may not always be possible to inform the patient or
referring physician prior to GBCA administration. If the decision is made to administer a
GBCA to a patient at increased risk for developing NSF, the supervising radiologist
(including the name) should document the reason for the examination and the rationale
for use of intravenous GBCA.
• Group I agents, the GBCAs that have been most often associated with NSF, have been
contraindicated by the FDA in these patients.
• Alternative agents should be used. The lowest possible dose of GBCA required to obtain
the needed clinical information should be used, and it should generally not exceed the
recommended single dose

46. Additional Specific Recommendations for Specific Groups of Patients
Patients with End-Stage Renal disease and on dialysis
• If a contrast-enhanced cross-sectional imaging study is required in an anuric patient with
no residual renal function, it would be reasonable to consider administering iodinated
contrast media and performing a CT rather than an MRI.
• If a contrast-enhanced MR examination must be performed in a patient with end-stage
renal disease on chronic dialysis, injection of group I agents is contraindicated.
• Also, use of the lowest possible dose needed to obtain a diagnostic study is
recommended and is appropriate.
• GBCA-enhanced MRI examinations be performed as closely before hemodialysis as is
possible, as prompt post-procedural hemodialysis, although unproven to date, may
reduce the likelihood that NSF will develop.
• Because it may be difficult for a dialysis center to alter dialysis schedules at the request of
imaging departments, it may be more feasible for elective imaging studies to be timed to
precede a scheduled dialysis session.
• Some experts recommend several dialysis sessions following GBCA administration, with
use of prolonged dialysis times and increased flow rates and volumes to facilitate GBCA

47. Peritoneal dialysis probably provides less potential NSF risk reduction compared to
hemodialysis and should not be considered protective.
Patients with CKD 4 or 5 (eGFR < 30 ml/min/1.73 m2) not on chronic dialysis
• The correct course of action in this patient group is problematic, as administration of
iodinated contrast media for CT may lead to further deterioration of renal function, while
administration of GBCA for MRI could result in NSF.
• It is recommended that any GBCA be avoided in this patient group. However if GBCA
enhanced MRI is deemed essential, use of the lowest possible dose needed to obtain a
diagnostic study is recommended
• Although there is no absolute proof that any GBCA is completely safe in this patient
group, group I agents have been contraindicated.

48. Patients with CKD 3 (eGFR 30 to 59 ml/min/1.73 m2)
NSF developing after GBCA administration to patients with eGFR > 30 ml/min/1.73 m2 is
exceedingly rare.
However, eGFR determinations may fluctuate from one day to the next (with an eGFR level
just above 30 on one day changing to an eGFR below 30 on another day).
It is for this reason that the precautions described for CKD4 and CKD5 patients are also
recommended for inpatients with an eGFR < 40 ml min/1.73 m2.
In comparison, no special precautions are required in patients with an eGFR of 40 to 59 ml/
min/1.73 m2.
Patients with CKD 1 or 2 (eGFR 60 to 119 ml min/1.73 m2)
There is no evidence that patients in these groups are at increased risk of developing NSF.
Current consensus is that any GBCA can be administered safely to these patients.

49. Patients with acute kidney injury (AKI)
• Patients with AKI who have been exposed to GBCA are at risk for developing NSF.
• Due to the temporal lag between eGFR (which is calculated using serum creatinine values)
and actual glomerular filtration rates, it is not possible to determine whether a given
patient has AKI based on a single eGFR determination.
• Accordingly, caution should be exercised in use of GBCA in patients with known or
suspected AKI regardless of measured serum creatinine or calculated eGFR values.
• GBCA should only be administered to these patients if absolutely necessary.
• When GBCA administration is required, agents associated with the greatest apparent NSF-
associated risk should be avoided.

50. OTHER REACTIONS TO GBCAs
• Gadolinium deposition in brain –
• Recently, residual gadolinium has been found within the brain tissue of patients
who received multiple doses of GBCAs over their lifetimes.
• For reasons that remain unclear, gadolinium deposition appears to occur
preferentially in certain specific areas of the brain, even in the absence of clinically
evident disease and in the setting of an intact blood brain barrier.
• Such deposition is not expected, and led the FDA to publish a Safety Alert in July of
2015 indicating that they were actively investigating the risk and clinical significance
of these gadolinium deposits.
• To date, no adverse health effects have been uncovered, but the radiology
community has initiated a rigorous investigation.

51. Breath-holding Difficulty with Gadoxetate Disodium
• Several studies have noted that gadoxetate disodium may be associated with transient
severe respiratory motion-related artifact that manifests in the arterial phase of
dynamic T1-weighted gradient echo imaging and resolves shortly thereafter.
• This manifestation has been described as “transient dyspnea”.
• At one institution, patient surveys showed that significantly more patients complained
of subjective shortness of breath following gadoxetate disodium compared to
gadobenate dimeglumine exposure.
• The reported rate of occurrence of “transient dyspnea” has varied by site, imaging
acquisition parameters, and administered volume, ranging from 4% to 14%
• It’s a physiological reaction – not related to allergic bronchospasm.
• At risk – COPD, Large volume, previous such episode

52. • GBCAs in Sickle cell disease - Safe. No in vivo vasoocclusive effect has been
documented although in vito alignment of HbS RBCs has been shown.
• Extravasation – GBCAs have a low risk for extravasation and low risk of
compartment syndrome as low volume is used.
• Serum Calcium levels and GBCAs - Only affect lab testing, not actual serum calcium
levels.
• GBCAs have not been approved by US-FDA for use with power injector .
• Not Recommended for Off-label use.

53. Children
• At this time few pediatric cases of NSF have been reported, and no cases have been
reported in children under the age of 6 years.
• Nevertheless, there is not enough data to demonstrate that NSF is less likely to occur
in children than in adults with similarly significant renal disease.
• Therefore, it is prudent to follow the same guidelines for adult and pediatric patients
as described in the remainder of this document.
• It should be noted, however, that eGFR values in certain premature infants and
neonates may be < 30 ml/min/1.73 m2 simply due to immature renal function (and
not due to pathologic renal impairment).
• In these individuals, caution should still be used when administering GBCAs, although
an eGFR value < 30 ml/min/1.73 m2 should not be considered an absolute
contraindication to GBCA administration.

54. SPECIAL SCENARIOS
1. Iodinated contrast media in patients on Renal Dialysis
• Contrast media are not protein-bound, have relatively low molecular weight – readily
cleared by dialysis.
• Urgent dialysis is not needed after contrast injection – unless the volume is very large or
there is an underlying cardiac dysfunction.
• Patients with ESRD and anuria can receive iodinated contrast media – kindneys are
already non-functioning.
• Risk of osmotic overload with the use of intravascular contrast media – pulmonary
edema and anasarca
• Take home message – As low as possible dose of contrast media as necessary to achieve
diagnostic goals.

55. SERUM CREATININE RECOMMENDATIONS
<1.5 mg/dl Can use ionic or nonionic contrast
1.5 – 2 mg/dl Use non-ionic contrast
2-2.5 mg/dl Use non-ionic contrast if absolutely
necessary, Avoid contrast in diabetics
> 2.5 mg/dl No contrast to be given
Recommendations based on serum creatinine levels

56. 2. Contrast administration in Pregnancy
• Contrast agents cross the placenta and enter the fetus at clinical doses
• There is no conclusive evidence to support or refute the use of contrast media in
pregnancy
• Recommendation of ACR Committee on Drugs and Contrast media
A. The Radiologist should confer with the referring physician and document
in the radiology report:
I. The information requested cannot be obtained without
contrast use or by an alternative modality ( e.g. USG)
II. The information requested has implications on the care of the
patient and the fetus during pregnancy
III. The referring physician is of the opinion that it is not prudent
to wait to obtain this information until after the patient is not
pregnant.

57. B. It is recommended that a written and informed consent is obtained
from the pregnant patient undergoing a procedure which requires the
use of ionizing radiation and iodinated contrast that they understand
the risk and benefits of the procedure to be performed and the
alternative diagnostic options available to them and that they whish
to proceed.
3. Contrast administration and lactation
• < 1% of contrast medium is excreted in breast milk and of that <1% is absorbed
by the baby’s gut.
• Thus it is safe to continue breast feeding after contrast administration.
• In case the parents are apprehensive regarding any potential ill-effects, the
mother may choose to refrain from breast feeding for 24 hours with active
expression of milk from both breasts.
• Expressed milk before the administration of the contrast agent may be used
during this period

58. 4. Contrast administration and Metformin
• Metformin is a biguanide oral hypoglycemic agent used in the management of
Type 2 Diabetes Mellitus.
• It is excreted by the kidneys by both glomerular filtration as well as tubular
secretion with 90% excretion achieved within 24 hours.
• Metformin appears to increase the production of lactic acid by the intestines.
• Any condition which will decrease the Metformin excretion or increase blood
lactate levels are risk factors for lactic acidosis.
• Use of metformin in renal insufficiency is a major risk factor for lactic acidosis .
• Features – vomiting, diarrhea, decreased level of conciousness – may be fatal
• Measures to prevent CIN should be instituted along with recommendations for the
use of contrast media in renal insufficiency.
• Co-morbid conditions – liver dysfunction, alcohol, decreased lactate metabolism,
anaerobic metabolism, sepsis, MI, peripheral vascular disease

59. RECOMMENDATIONS FOR THE USE OF CONTRAST MEDIA AND METFORMIN
CATEGORY 1 CATEGORY 2
• Normal renal function
• No AKI
• GFR ≥30 ml/min/1.73 m2
• No reason to discontinue
metformin
• AKI
• GFR < 30 ml/min/1.73m2
• IA procedure that risks
embolism to renal arteries
• Discontinue prior to or at
the time of procedure.
• Restart only afer
documentation of normal
Renal function

60. 5. Contrast administration and IL-2 therapy
• Always ask the oncologist for a possible IL-2 therapy
• Risks involved (12% patients) – rash, flu-like symptoms, pruritis, hypotension,
tachycardia, joint pains – few may require hospitalization.
• Steroids cannot be given – counteract the IL-2 therapeutic benefit.
• If patient has a previous history of contrast reaction – do not give contrast until
absolutely necessary.
• Monitor patient for 2 hrs – if uneventful – send home
6. Contrast administration and thyroid dysfunction
• Manifest active hyperthyroidism is an absolute contraindication for radiographic
contrast administration
• Patients at risk : Grave’s disease and multinodular goitre with thyroid autonomy –
esp. in elderly/patients living in iodine deficient regions

61. • Contrast use may trigger “Thyroid storm” – although rare
• After iodinated contrast administration – patient becomes unfit for Thyroid
scintigraphy and radioiodine therapy for 8 weeks
• Prophylaxis for contrast induced- thyrotoxicosis
I. Elective contrast procedure – Sodium Perchlorate 300 mg x 3 times a
day. To be started 1 day before and continue for 8-14 days
II. Emergency procedure – Sodim perchlorate 800 mg just before
procedure. Continue 300 mg x 3 times a day for next 8-14 days
7 . Contrast administration in Pheochromocytoma and paraganglioma
• Only a theoretic risk of hypertensive crisis due to catecholamine release
• Not supported by evidence
• Avoid contrast injection into adrenals or renal artery - this may cause
hypertensive crisis.

62. CONTRAST AND DRUG INTERACTIONS
• Drugs which enhance the renal effect of contrast – NSAIDs, cyclosporine, Cisplatin,
Aminoglycosides, vancomycin
• Drugs which enhance diuretic effect of contrast - Acetazolamide, furosemide,
Spironolactone
• Drugs which enhance allergic reactions – Beta-blockers, IL-2, Interferons and
Hydralazine (can provoke SLE-like syndrome)
• Drugs which enhance the negative ionotropic effect of contrast agent – CCB, digoxin.

63. Delayed Adverse effects of Iodinated contrast media
• Occur from 30-60 min to 1 week following contrast exposure – majority between
3hrs to 2 days.
• Most frequent – allergic-like cutaneous reaction. Most frequent in those with
previous Hx of asthma, previous contrast reactions and other allergies.
• Manifestation of Delayed cutaneous reactions – urticaria and/or persistent rash,
generalised exantheatous pustulosis, maculopapular rash etc.
• Few case may resemble SJS, TEN and cutaneous vasculitis.
• Non-cutaneous delayed reactions include – nausea, vomiting, fever, drowsiness
and headache.
• “IODINE MUMPS (iodine-related sialoadenopathy) and syndrome of
Polyarthropathy are two additional, rare delayed reactions which have been
described – more frequent in patients with renal dysfunction.
• LOCM have a lower incidence of delayed reactions that IOCM
• No prophylaxis is recommended

64. CONCLUSIONS AND SUMMARY
• Always weigh the Risk-benefit ratio.
• Look for alternative diagnostic modality if available in high-risk cases
• Discuss the case with the referring physician, patient and attendants and record the
discussion in patient’s notes.
• Routine test dose not recommended – but 1 ml of IV or ID test dose may be used in
high risk cases – but may not be useful for all reactions.
• Pre-medication in high-risk cases
• Informed consent before the procedure.
• Keep all the equipment and trained personel ready before, during and after
administration of contrast.
• Adequate hydration for all patients, esp, those with renal dysfunction
• LOCM/IOCM preferred over HOCM

65. • Staff involved in a procedure requiring administration of contrast agents must be
adequately trained to recognize and manage contrast reactions.
• All contrast reactions must be recorded and reported to the pharmacovigilance
department.
• Patient must not be left alone any time during and atleast 15-30 mins after
contrast administration.
• Dosage of contrast must be as low as possible so as to obtain a diagnostically
adequate study.

66. REFERENCES AND FURTHER READING
1. ACR Committee on Drugs and contrast Media; ACR manual on contrast media.
Ver 10.2, 2016
2. ACR Contrast manual 2012 and 2013.
3. AIIMS-MAMC-PGI Series – Recent Advances and Genitourinary system
4. Grainger and Allison’s Textbook of Radiology, 6TH Ed
5. Sutton’s Textbook of Radiology, 7th Ed.
6. Brant and Helms, Fundamentals of Diagnostic Radiology
7. Peer S, Gojwari TA, Choh NA. Incidence of Contrast Induced
Nephropathy : a Prospective study, 143 pages, Sher-i-Kashmir Institute
of Medical Sciences (Deemed University), 2016

67. THANK YOU!