• an iodinated contrast agent is a form of a radiocontrast agent (radiographic dye) containing iodine, which enhances the visibility of vascular structures and organs during radiographic procedures
  • routes of administration:
    • intravenous
    • intraarterial
    • oral
    • others (rectal, cystourethral, and intra-articular)
  • main indications in neuroradiology:
    • contrast-enhanced CT
    • CT angiography/venography
    • DSA (diagnostic/interventional)

The main principles of contrast agent administration

  • check personal history to detect patients at risk
    • search for allergies, history of bronchial asthma, and previous postcontrast complications ( itching, acute rash, bronchospasm, stridor, laryngeal edema, and anaphylaxis)
    • search for nephropathy and diabetes mellitus (including metformin use)
  • allergies
    • premedicate the high-risk patients with corticosteroids
      • at least 6-12 hours before the administration of the contrast agent
      • it is the referring physician’s responsibility to secure the correct premedication
    • with a previous severe allergic reaction, the presence of an anesthesiologist is advisable
  • verify current serum creatinine levels and calculate ClCr

Prior the procedure

  • ensure adequate hydration 24 h prior to the examination
    • PO or IV (especially in the elderly and in the summer months)
  • insert intravenous cannula – at least 20G (pink)
  • double-check that the patient has no allergies/adverse reactions or is premedicated
  • patient should be fasted (> 4h), except for emergent situations (e.g. CTA in an acute stroke)
    • in patients with diabetes, do not administer insulin and PAD in the morning (they should take medication and food with them)
    • limit oral intake to only small amounts of fluids (e.g. 100 ml/hr) 4 hrs before the examination

After the procedure

  • observation (advice patients about possible adverse events)
  • sufficient hydration for the next 24h (inform out-patients)
  • patients with diabetes can have some snack after the examination and they can inject insulin or take PAD (except for metformin in selected cases)
    • if no complications (nausea, vomiting) occur within 48 h, metformin therapy can be restarted
    • in patients with renal impairment, better check blood samples before starting metformin
  • with transient postcontrast nephropathy, metformin may accumulate in the body (it is excreted by the kidneys) which increases the risk of lactic acidosis
  • metformin is generally not prescribed to patients with nephropathy, so the risk of such adverse reaction is low
    • there have been no reports of lactic acidosis following intravenous iodinated contrast medium administration in patients properly selected for metformin administration
  • in patients with no evidence of AKI (acute kidney injury) and with GFR ≥30 mL / min/1.73m2 (0.5 ml/s), there is no need to discontinue metformin either prior to or following the intravenous administration of iodinated contrast media, nor is there an obligatory need to reassess the patient’s renal function following the test or procedure
  • patients taking metformin who have AKI or CKD stage IV or stage V (GFR < 30 mL / min/1.73m2, 0.5 ml/s), or are undergoing arterial catheter studies that might cause embolism to the renal arteries, metformin should be temporarily discontinued at the time of or prior to the procedure, and withheld for 48 hours after the procedure and re-instituted after renal function has been re-evaluated and found normal (ACR recommendation)

Pregnancy

  • the safety of nonionic contrast agents has not been sufficiently established in pregnant women – use only if absolutely required (acute stroke management, etc.)
    • animal studies have reported no teratogenic or mutagenic effects
  • American Society of Radiology recommends mother to sign the informed consent before administering a contrast agent [Shin, 2011]
  • there have been concerns about the potential harm of free iodide on the fetal thyroid gland (→ fetal hypothyroidism), but multiple studies have shown that a single dose of intravenously administered iodinated contrast medium to a pregnant mother does not affect neonatal thyroid function
  • I can perform CTA (lower burden compared to CTP)
  • CT perfusion is better to omit because of the increased dose of radiation and contrast agent

Lactation

  • iodinated contrast administration is considered safe for both the mother and child
  • contrast agents are barely excreted in breast milk (approx. 1%)
  • some authors recommend to postpone the breastfeeding for 24 h after contrast administration (with continued milk extraction such as by a breast pump during that period) (American College of Radiology guidelines)
  • beta-blockers have been assumed to increase the risk of contrast medium-induced adverse reactions
  • due to recent investigations, beta-blockers do not increase the frequency of adverse reactions

Contrast agents overview

  • water-soluble iodinated contrast agents are commonly used in neuroradiology
  • the iodine may be bound either in an organic (non-ionic) compound or an ionic compound
    • ionic agents may cause additional complications because of hyperosmolality
    • non-ionic agents have fewer side effects as they do not dissociate into component molecules – available in concentrations 240-400 mg iodine/mL – higher concentration yield a greater peak of enhancement but are more viscous
  • ionic (e.g., Telebrix, Gastrografin, Cystografin, Conray) – cheaper, hyperosmolar, higher risk of adverse reactions compared to non-ionic
    • they include a benzene ring with three iodine atoms and a side chain containing a carboxylic acid group
    • used for gastrointestinal and cystourethral examinations
  • non-ionic monomers – iodine atoms are more tightly bound in their molecule, are slightly hyperosmolar (700-900), have low viscosity, and lower risk of allergic reactions
    • preferred for intravascular and intrathecal administration
    • iopromide (Ultravist 370), iomeprol (Iomeron), iohexol (Omnipaque 350)
  • non-ionic dimers – iso-osmolar, lower risk of post-contrast nephropathy than non-ionic monomers, low risk of an allergic reaction, same as the previous group. Their disadvantage is a higher viscosity
    • iodixanol (Visipaque 320

Definition of a patient at risk

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Maximum contrast agent dose

  • In patients with normal renal function (serum creatinine < 100 µmol/l) and adequate hydration, the upper guideline dose limit is up to 300 ml of contrast agent with a concentration of 300 mg iodine/ml
  • with impaired renal function (serum creatinine 130-300 µmol/l), the maximum recommended amount of contrast agent is < 150 ml
  • the maximum dose can be calculated according to the formula:

contrast agent volume in ml (300 mg iodine per ml) = [5 x weight (max 60 kg)] / [serum creatinine level in µmol/l / 88]

Premedication

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Complications

Contrast media hypersensitivity reaction

Acute reaction
  • anaphylactoid reactions, erroneously referred to as contrast allergies, are a group of symptoms and signs, with different degrees of severity

    • most of the reactions are not immune-mediated (do not involve antibodies) and are dose-independent = these effects should be referred as contrast media hypersensitivity reactions
    • symptoms and therapy are the same as with allergic anaphylactic reaction
  • currently used non-ionic low-osmolar contrast agents are safer than the older high-osmolar or ionic contrast media
  • reactions are most commonly seen after the intravascular administration
  • history of a previous reaction to iodinated contrast media (200x increased risk)
    • get details regarding previous reaction and consider alternative imaging method (e.g. non-contrasted study, ultrasound, MRI)
  • hyperthyroidism
  • family history of hypersensitivity reaction to iodinated contrast media (14x increased risk)
  • allergic diseases, including asthma (6-10x increased risk)
    • not a contraindication – risk of severe reactions is small with non-ionic and low-osmolality iodinated contrast
  • history of multiple allergies
    • not a contraindication, get detailed history
    • shellfish allergy and skin irritation/”allergy” to topical iodine antiseptic is not associated with an increased risk of contrast media adverse reactions
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Delayed reaction
  • rare, commonly non-severe complication
  • usually occurs > 1h (up to a week) after contrast administration
  • most commonly presented as a mild-moderate rash, urticaria, or angioedema
  • patients with a previous reaction are predisposed
  • treatment is symptomatic

Contrast induced nephropathy (CIN)

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Contrast induced encephalopathy (CIE)

Other side effects

Patients with thyreopathy
  • for the general population, routine screening with thyroid function tests is generally not feasible
  • in patients with a history of hyperthyroidism, thyrotoxicosis, or thyroiditis, administration of iodine contrast can lead to a thyrotoxic crisis ⇒ consult an endocrinologist
  • in case of thyroid hypofunction, an iodinated contrast agent can be administered
  • iodinated contrast agents reduce the ability of thyroid tissue to uptake radioisotopes of iodine, thus thyroid scintigraphy diagnosis is affected for more > 2 weeks
  • if thyroid cancer is suspected, avoid an iodinated contrast agent because subsequent treatment with radioactive iodine would be not possible (up to six months after the administration)
Patient with pheochromocytoma
  • administration of an iodinated contrast agent can lead to a hypertensive crisis; it is recommended to administer alpha-blockers
  • choose another imaging method (MRI)
Contrast media extravasation
  • symptoms may vary from local pain and tenderness up to skin ulcers, necrosis, or even acute compartment syndrome
  • small extravasate results in minimal swelling or erythema and requires no therapy; with larger volumes, apply a cold compression with an ice pack and elevate the affected extremity
    • discontinue the contrast infusion and notify the radiologist
    • attempted aspiration of the extravasation is not effective
  • follow up the patient in the next few days until resolving the signs and symptoms
  • critical symptoms (increasing swelling and pain, ulceration, altered tissue perfusion) require surgical intervention
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