Diagnostic Imaging Pathways - Contrast Agents

Iodinated Contrast for CT Scans

In Australia, intravascular contrast media for radiographic procedures are almost exclusively non-ionic (as opposed to ionic) contrast agents. Non-ionic agents are thought to be up to 10 times safer than ionic contrast media. Uses of contrast include intravenous urography, contrast-enhanced CT scans, venography and angiography.

Allergy-Like Reactions

The vast majority of patients tolerate intravascular non-ionic contrast injection well. Severe reactions including shock from anaphylactoid reactions do occur very rarely in about 1 in every 25,000 injections. The risk of a fatal reaction is estimated at 1 in 170,000. These reactions are not dose-dependent and do not involve antibody formation to contrast media. The clinical features of anaphylactoid reactions usually manifest within 60 minutes, with the majority developing in the first 5 minutes. Delayed reactions occur up to one week post-injection and generally involve skin rashes without bronchospasm or laryngeal oedema. Symptoms vary between patients and can be classified into system-based categories:

  • Cutaneous
    • Generalised pruritus, flushing
    • Urticaria (hives) or angioedema
  • Respiratory
    • Laryngeal oedema (hoarseness, stridor)
    • Bronchospasm (shortness of breath, wheezing)
    • Respiratory failure
  • Cardiovascular
    • Arrhythmias
    • Conduction disturbances
    • Vasodilatation, increased vascular permeability
    • Hypotension, anaphylactic shock
  • Neurological
    • Syncope, dizziness
    • Seizures
  • Gastrointestinal
    • Nausea, vomiting, diarrhoea
    • Abdominal cramps

While the risk of severe reaction is largely unpredictable, factors that predispose to a reaction include: a history of a previous generalized contrast reaction, an atopic history and a history of asthma. B-blockers have also been shown to increase the risk of anaphylactoid reactions and bronchospasm (This population may be resistant to adrenaline used in resuscitation and IM glucagon should be used if adrenaline is ineffective). Patients at risk should receive non-ionic contrast agents if iodinated contrast material is needed. Use of pre-medication is variable and opinion is divided. Corticosteroids ± antihistamines (eg. prednisolone 50mg orally taken 13 and 1 hour(s) before contrast administration ± diphenhydramine 50mg 1 hour before contrast) have been the most widely recommended agents but are not effective if commenced less than 6 hours before the procedure. 1,7 There is also insufficient evidence to show that pre-medication decreases the incidence of life-threatening reactions. 2
The feeling of warmth and a metallic taste is relatively common with administration of intravenous contrast and does not indicate that an allergic reaction has occurred. Patients should be made aware of the potential risks of contrast media prior to the procedure. 3

Contrast Extravasation

Contrast extravasation is an uncommon and generally benign complication of iodinated contrast injection. It occurs when there is leakage of iodinated contrast material out of the vein and into the surrounding subcutaneous tissues. Because iodinated contrast is cytotoxic (harmful to tissues), it can cause a range of complications. However, it is uncommon, occurring in less than 1 in 100 scans requiring contrast.

The majority of patients who have contrast extravasation will only exhibit mild symptoms. These manifest as an acute local inflammatory response, including tissue oedema, erythema, stinging and tenderness. Some patients may not experience any discomfort. More severe symptoms may also occur such as compartment syndromes, skin ulceration and tissue necrosis. Compartment syndromes occur when there is mechanical compression of the nerves, blood vessels and muscles within a closed compartment within the body. If the compression is not relieved, it can lead to tissue death. It can occur in contrast extravasation after extravasation of large volumes of contrast, or when the extravasation occurs in smaller tissue compartments (such as the back of the wrist). This may require surgery to relieve the pressure.

Contrast extravasation and severe sequelae from them are very rare. Wang et al. found only 475 incidences of contrast extravasation out of nearly 70 000 contrast injections (0.7% incidence). Of the 475, only 12 patients developed moderate or severe injuries as a result of extravasation. Only one patient required surgery to relieve a compartment syndrome involving the dorsum of her hand. The patient had no residual functional impairment on follow-up.

Unfortunately, there is no clear consensus as to the most effective treatment for contrast extravasation. Generally, conservative treatments such as limb elevation, cold compresses & application of lanolin are adequate in most cases. The patient should be reviewed by a doctor and remain in hospital for observation for at least 2-4 hours. If the doctor is satisfied that the initial signs & symptoms have improved, or if no new symptoms have developed, then the patient may discharged. They should be given clear instructions to re-present to ED if there is any worsening or development of new symptoms. If the patient's symptoms worsen or new neurological/vascular symptoms develop during the observation period, they should be referred to the plastic surgery team for urgent review.

Contrast Induced Nephropathy

The use of intravenous contrast medium in radiological examinations carries an overall risk of contrast-induced nephropathy of approximately 1.2-2.7%. Contrast-induced nephropathy is defined as impairment of renal function indicated by a rise in serum creatinine by more than 25% occuring within 3 days of IV contrast administration in the absence of another aetiology.1Most cases recover spontaneously within 14 days although a minority can progress to chronic renal failure and dialysis. The factors that increase the risk of intravascular contrast media-induced nephropathy with a marked decline in renal function include:

  • Underlying renal impairment (plasma creatinine >132 mmol/L) or renal disease
  • Diabetes Mellitus
  • Age > 70 years
  • Use of nephrotoxic medications (eg NSAIDS, diuretics, ACE inhibitors, aminoglycosides, amphotericin, antineoplastics, cyclosporin, lithium, methotrexate, vancomycin)
  • Cardiac failure
  • Hypertension
  • Gout
  • Dehydration
  • Previous renal surgery
  • Cirrhosis of the liver
  • Intra-arterial contrast administration, large doses of contrast and repeated doses of contrast

Renal function can be assessed by using the plasma/serum creatinine and estimating creatine clearance using the Cockcroft-Gault equation (shown below). The Modified Diet in Renal Disease (MDRD) derived eGFR commonly reported in association with serum creatinine in laboratory reports does not take into account patient weight and is unreliable for those who are extremely overweight or underweight. 10

The Cockcroft-Gault formula using µmol/l: 4

Creatinine Clearance (ml/min) = (140 - age (yrs)) x mass (kg) [x 1.23 if male] [x 1.04 if female]
serum creatinine (µmol/l)

The Cockcroft-Gault formula using mg/dl:

Creatinine Clearance (ml/min) = (140 - age (yrs)) x mass (kg) [x 0.85 if female]
72 x serum creatinine (mg/dl)

Note: Normal creatinine clearance is 95±20 mL/min in women and 120±25 mL/min in men.

The probability of developing contrast induced nephropathy requiring dialysis varies according to the pre-existing renal impairment. 5

Creatinine Clearance (mL/min)Risk in Non-Diabetics (%)Risk in Diabetics (%)
50 0.04 0.2
40 0.3 2
30 2 10
20 12 43
10 48 84

IV Iodinated Contract Media diagram

Evidence suggests that a small, transient rise in plasma creatinine is relatively common following administration of intravenous contrast media. Patients with normal or borderline-normal renal function generally do not require precautionary measures. In patients with a plasma/serum creatinine of >250-300µmol/L, iodinated contrast is contraindicated and should be avoided. For patients with a plasma/serum creatinine >150mmol/L, strategies to reduce the risk of contrast nephropathy include: 3,6

  • Considering alternatives to the use of IV iodinated contrast, such as non-contrast CT, ultrasound, or MRI.
  • Use of low osmolality or iso-osmolar contrast media.
  • Hydration: intravenous hydration with normal saline is preferable to oral hydration at a rate of at least 1-2 mL/hr/per kg body weight and should be commenced at least 4 hours prior to the procedure and continued for 4-24 hours post procedure. This may not be appropriate in certain clinical situations (eg. congestive heart failure) and caution must be applied.
  • Nephrotoxic medications should be ceased for at least 24 hours before and after where possible.
  • N-Acetyl Cysteine: its use is controversial and there is variable evidence regarding its reno-protective effect. A renal physician should be consulted regarding its use.

Patients with Type II diabetes mellitus may be taking the oral hypoglycaemic medication metformin. It is renally excreted in its active form, but with increasing renal impairment, there is a risk of lactic acidosis (a form of metabolic acidosis) due to metformin accumulation. Lactic acidosis is a medical emergency and requires urgent treatment. The risk increases with the degree of renal dysfunction and the patient's age. After receiving iodinated contrast media, some patients may experience an acute renal impairment. This may also result in metformin accumulation and lactic acidosis. The absolute risk remains low, however there are guidelines to prevent this from occurring. 7

In patients with renal impairment who require iodinated contrast:

  • Metformin should ideally be ceased 48 hours prior to the procedure.
  • The patient should be kept well hydrated.
  • Re-check renal function and serum creatinine after the procedure and recommence patient on metformin 48 hours post-procedure if their renal function is unchanged.

Patients with normal renal function do not need to cease their metformin pre-procedure or re-check renal function post-procedure. 7

Contrast Induced Thyrotoxicosis

Thyrotoxicosis secondary to iodinated contrast material is rare but may occur in patients with abnormal thyroid function. Patients whom manifest hyperthyroidism should not be given iodinated contrast material. Patients with Graves’ disease, multinodular goiter or other forms of thyroid autonomy, especially if they are elderly and/or live in areas of dietary iodine deficiency are at risk of iodinated contrast induced thyrotoxicosis. 8 These patients should be monitored by an endocrinologist after administration of iodinated contrast medium and in selected high-risk patients, prophylaxis prescribed by an endocrinologist may be warranted. Intravenous cholangiographic contrast media should not be given to patients at risk. 8

Iodinated Contrast Use in Pregnancy and Lactation

In exceptional circumstances, when contrast use is deemed necessary, iodinated contrast media may be given to the pregnant mother. The theoretical risk of contrast induced hypothyroidism within the foetus has not been validated and foetal exposure to iodinated contrast media and any associated free iodide is likely to be small and relatively short-lived. Although no adverse foetal effects due to contrast administration during pregnancy have been proven, current guidelines recommend that all neonates should receive thyroid function testing in the first week of life where the mother has received iodinated contrast material in accordance with current standard paediatric care. 9

European guidelines have stated that cessation of breast feeding following iodinated contrast material is not required. 9 The amount of contrast media excreted in breast milk is very small and the absorbed dose to the foetus even smaller. The likelihood of either direct toxicity or allergic reaction is therefore extremely low. However, as with other drugs and foodstuffs, the taste of milk may be altered.

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