PRESENTED BY

Dr Sameer Peer

MODERATOR

Dr Naseer A Choh(MD) Associate Professor

SENIOR RESIDENT i/c

Dr Azhar Khan(MD) Senior Resident

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.

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.

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.

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

Types of adverse reactions

IDIOSYNCRATIC NONIDIOSYNCRATIC

UNRELATED CHEMOTOXIC RELATED OSMOLARITY RELATED

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

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.

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

A – AirwayB – BreathingC – CirculationD – DisabilityE – Exposure

Call for help immediately while resuscitating – do not hesitate

INITIAL APPROACH – ABCDE of Critical care

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)

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

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%

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

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

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

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

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

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

< 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

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

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.

MECHANISM OF CIN

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

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%.

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

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

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.

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.

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

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

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

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

The logistic regression equation for this model was obtained as follows:Y = ∑βxWhere, 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.

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%

Nephrogenic systemic fibrosisDefinition

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.

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.

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.

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.

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.

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).

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

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

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 clearance.

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.

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.

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.

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.

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

• 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.

Children

• At this time few pediatric cases of NSF have been reported, and no cases have beenreported 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.

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.

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

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.

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

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

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

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

• 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.

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.

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

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

• 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.

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

THANK YOU!