Intravenous radiographic contrast induced adverse

reactions – their causes , prevention and relief measures :

 There are inherent risks associated with the use of contrast media.
 Adverse side effects and adverse drug reactions (ADRs) can be a direct result
from the use of contrast media and vary from minor disturbances to severe,
life-threatening situations..
 Adverse drug reactions (ADR) :
Two broad categories: a.) Idiosyncratic anaphylactoid (IA)
and b) Nonidiosyncratic (NI) reactions.

Idiosyncratic Anaphylactoid (IA) :

 Potentially fatal and can occur without any predictable or predisposing factors.
Approximately 85% of IA reactions occur during or immediately after injection
of IRCM.
 More common in patients with a prior ADR to contrast media, asthmatics,
diabetics, impaired renal function , diminished cardiac function, and those on
β-adrenergic blockers.
 The exact mechanism of IA reactions is not known but is thought to be a
combination of systemic effects.
 IA reactions have not been shown to result from a true IgE antibody
immunologic reaction to the contrast media.
 At least four mechanisms may play a role in IA reactions:
 Release of vasoactive substances including histamine
 Activation of physiologic cascades including complement, kinin,
coagulation, and fibrinolytic systems;
 Inhibition of enzymes including cholinesterase, which may cause prolonged
vagal stimulation
 Patient’s own anxiety and fear of the actual procedure.
 IA reactions are not dose dependent.
Severe reactions have been reported after only 1 ml injected at the beginning of
the procedure and also after completion of a full dose despite no reaction to the
initial test dose..

Nonidiosyncratic (NI) reactions :

 Reactions are dose dependent and consequently related to the osmolality,
concentration, volume, and injection rate of the IRCM.
 Because the concentration of absorbed or free iodine is low, only patients with
an underlying iodine deficiency are at risk for increased intake of iodine during
contrast imaging.
 Patients with endemic goiter may develop thyrotoxicosis.
 The hyperosmolar contrast media (HOCM)
 Have an osmolality that is five times greater than physiologic osmolality of
body cells (300 mOsm/kg water).
 Associated with erythrocyte damage, endothelial damage, vasodilation,
hypervolemia, interruption of the blood-brain barrier, and cardiac depression.
 The low osmotic contrast media (LOCM)
 Have an osmolality the same as or slightly higher than physiologic
osmolality
 Associated with fewer ADRs and toxic events.
 All contrast ADRs are more common with HOCM (12%) compared with
LOCM (3%) .
Risk factors :
 At greatest risk for contrast-induced nephropathy are those with
 Diabetes mellitus and dehydration.
 Type II diabetics with renal insufficiency on oral metformin are at risk for
developing biguanide lactic acidosis after IV contrast.
 OTHER RISK FACTORS
 Previous adverse reactions
 History of asthma
 Severe cardiac disease
 Renal insufficiency
 Sickle cell anemia
 Anxiety, apprehension
 Hyperthyroidism
 Presence of adrenal pheochromocytoma.

Prevention :
 No known premedication strategy will eliminate the risk of a severe adverse
reaction to IRCM.
 Patients at high risk should be premedicated with corticosteroids and possibly
antihistamines 12 to 24 hours before and after use of IRCM.
 LOCM can be used in these patients.
 Two commonly used regimens are ,
1 )Prednisone 50 mg by mouth at 13 hr, 7 hr, and 1 hr before contrast media
injection Plus diphenhydramine —50 mg IV, IM, or by mouth 1 hr before contrast
medium injection.
2) Methylprednisolone (Medrol) 32 mg by mouth 12 hr and 2 hr before contrast
media injection Plus diphenhydramine —50 mg IV, IM, or by mouth 1 hr before
contrast medium injection .
 Steroids should be given at least 6 hours before the injection of contrast media
regardless of the route of steroid administration.
 It is clear that administration for 3 hours or less before contrast does not
decrease adverse reactions .
 Supplemental administration of an H1 antihistamine (e.g., diphenhydramine),
orally or IV, may reduce the frequency of urticaria, angioedema, and respiratory
symptoms.
Special considerations :
Patients with type II diabetes mellitus on metformin oral biguanide
 Biguanide lactic acidosis presents with vomiting, diarrhea, and somnolence.
 This condition is fatal in approximately 50% of cases.
 Rare in patients with normal renal function. Patients with normal renal function
and no known comorbidities -- no need to discontinue metformin before IRCM .
 In patients with renal insufficiency, metformin should be discontinued the day
of the study and with held for 48 hours.
 Post procedure creatinine should be measured at 48 hours and metformin started
once kidney function is normal.
 It is not necessary to discontinue metformin before gadolinium-enhanced
magnetic resonance studies when the amount of gadolinium administered is in
the usual dose range of 0.1 to 0.3 mmol per kg of body weight .

Contrast induced nephropathy CIN :

CIN is defined as a rise in serum creatinine 25% above baseline, or more than
0.5 mg/dL within 3 days following exposure to contrast media, in the absence of
an alternative cause.
Risk factors
 Chronic kidney disease (creatinine clearance <60 mL/min)
 Diabetes mellitus, Dehydration
 Congestive heart failure, Ventricular ejection fraction less than 40%.
 Age
 Hypertension
 Low hematocrit
Non–patient-related causes
 High osmolar contrast agents
 Ionic contrast
 Increased contrast viscosity
 Large-contrast volume infusion.
Prevention of CIN
 Adequate hydration
 Bicarbonate,
 Iso or low osmolar contrast media
 N-acetylcysteine.
Dose of NAC : 600 to 1200 mg orally twice a day for 2 doses before the contrast
enhanced study and 2 doses after the procedure.
Furosemide was found to increase the risk of developing CIN.

MRI contrast agents

 Gadolinium-based contrast media (GBCM) are considered to have no
nephrotoxicity at approved dosages for MRI.
Nephrogenic Systemic fibrosis (NSF)
 Reported in patients with advanced renal insufficiency (glomerular filtration rate
[GFR] <30 mL/min).
 Fibrosing disease of the skin, subcutaneous tissues, lungs, esophagus, heart,
and skeletal muscles.
 Initial symptoms typically include skin thickening and /or pruritus.
 Affected patients develop contractures and joint immobility within days of
exposure.
 Death may result in some patients, presumably as a result of visceral organ
involvement.
 CKD patients have a 1% to 7% chance of developing NSF after MRI imaging
with gadolinium agents.
 Prevention
 Use of the lowest possible doses (needed to obtain a diagnostic study)
 Avoid gadodiamide and considering use of macrocyclic agents
Relief measures for ADR :
Minor Reactions :
 Nausea, flushing, pruritus, urticaria, headache ,and emesis after injection of
IRCM. Reactions are usually mild and do not require additional treatment.
 Arm pain can also result from venous spasm or infiltration of the media outside
the vein.
 An H1 receptor blocker like diphenhydramine (Benadryl) PO/IM/IV 1 to 2
mg/kg, up to 50 mg may be helpful

Intermediate Reactions :
 Worsening or more severe minor reactions including hypotension or
bronchospasm occur in 0.5% to 2% of patients.
 These are usually transient and do not need treatment. If necessary,
 4 to 10 mg of Chlorphenamine administered orally, IV, or IM;
 5 mg of Diazepam for anxiety;
 100 to 500 mg of Hydrocortisone IM or IV;
 Two - three puffs of beta-agonist inhalators for bronchospasm ;
metaproterenol , terbutaline or albuterol

Severe Reactions :
 Life-threatening reactions -- Approximately 1/1000 uses for high-osmolar
agents and are far less for Low-osmolar contrast media
 Both types agents mortality rates -- 1/170,000 uses .
 Severe reactions include seizure,laryngeal spasm, bronchospasm, pulmonary
edema, cardiac arrhythmia, respiratory collapse, or cardiac arrest .
 Rapid administration of epinephrine is the treatment of choice for severe
contrast reactions.
 Current guidelines recommend immediate delivery of 0.01 mg/kg of body
weight to a maximum of 0.5 mg of 1 : 1000 concentration of epinephrine,
injected IM in the lateral thigh as first-line treatment.
 Subcutaneous injection is much less effective.