• 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

  • review medical history to identify patients at risk
    • search for allergies, history of bronchial asthma, and previous postcontrast complications (pruritus, acute rash, bronchospasm, stridor, laryngeal edema, and anaphylaxis)
    • also search for nephropathy and diabetes mellitus (including metformin use)
  • allergies
    • premedicate high-risk patients with corticosteroids
      • at least 6-12 hours before the contrast administration
      • the referring physician is responsible for ensuring proper premedication
    • the presence of an anesthesiologist is recommended in patients with a history of severe allergic reaction
  • check current serum creatinine levels and calculate CrCl

Prior the procedure

  • ensure adequate hydration 24 hours before the examination
    • PO or IV (especially in older people and during the summer months)
  • insert intravenous cannula – at least 20G (pink)
  • double-check that the patient has no allergies/adverse reactions or is properly premedicated
  • patient should be fasted (> 4h), except in emergencies (e.g., CTA in an acute stroke)
    • patients with diabetes should not take 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/h) 4 hours before the procedure

After the procedure

  • observation (advise patients about possible adverse events)
  • sufficient hydration for the next 24 hours (inform outpatients)
  • patients with diabetes can eat some snacks 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 hours, metformin therapy can be resumed
    • in patients with renal impairment, it is better to check renal function before resuming 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 this 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 without evidence of AKI (acute kidney injury) and with a GFR ≥30 mL /min/1.73m2 (0.5 mL/s), there is no need to discontinue metformin before or after intravenous administration of iodinated contrast media, nor is there a need to reassess the patient’s renal function after the test or procedure
  • in 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, withheld for 48 hours after the procedure and resumed after renal function has been re-evaluated and found to be normal (ACR recommendation)


  • the safety of nonionic contrast agents in pregnant women is not well established and should be used only when absolutely necessary (acute stroke management, etc.)
    • no teratogenic or mutagenic effects have been reported in animal studies
  • the American Society of Radiology recommends that mothers provide informed consent for contrast administration [Shin, 2011]
  • there have been concerns about the potential harm of free iodide on the fetal thyroid gland (⇒ fetal hypothyroidism), but several studies have shown that a single dose of intravenous iodinated contrast given to a pregnant individual does not affect neonatal thyroid function
  • CTA can be performed (less burden compared to CTP)
  • CT perfusion should be avoided due to increased radiation and contrast dose


  • iodinated contrast administration is generally considered safe for both the mother and child
  • contrast media are minimally excreted in breast milk (~ 1% of the administered dose)
  • some authors recommend postponing breastfeeding for 24 hours after contrast administration (with continued milk extraction using a breast pump during this period) (American College of Radiology guidelines)
  • beta-blockers were thought to increase the risk of contrast media-related adverse events
  • recent studies have shown that beta-blockers do not increase the incidence of adverse events

Contrast agents overview

  • water-soluble iodinated contrast agents are commonly used in neuroradiology
  • the iodine may be bound in either an organic (nonionic) or ionic compound
    • ionic agents may cause additional complications because of hyperosmolality
    • nonionic agents have fewer side effects as they do not dissociate into component molecules – available in concentrations of 240-400 mg iodine/mL – higher concentrations yield a larger enhancement but are more viscous
  • ionic (e.g., Telebrix, Gastrografin, Cystografin, Conray) – cheaper, hyperosmolar, higher risk of adverse reactions compared to non-ionic agents
    • they include a benzene ring with three iodine atoms and a side chain containing a carboxylic acid group
    • used for gastrointestinal and cystourethral examinations
  • nonionic monomersiopromide (Ultravist 370), iomeprol (Iomeron), iohexol (Omnipaque 350)
    • iodine atoms are more tightly bound in their molecule
    • water-soluble, allowing it to be easily mixed with body fluids and distributed throughout the bloodstream for imaging purposes
    • slightly hyperosmolar (700-900) with low viscosity and lower risk of adverse reactions compared to older, high-osmolality ionic contrast agents
    • preferred for intravascular and intrathecal administration
  • nonionic dimersiodixanol (Visipaque 320)
    • an iso-osmolar agent with a lower risk of post-contrast nephropathy compared to non-ionic monomers
    • low risk of an allergic reaction, higher viscosity

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 dose usually ranges from 1 to 3 mL per kilogram (kg) of body weight
    • the exact dosage should be determined by the healthcare professional based on the individual patient’s needs and the specific imaging protocol being used
    • typically, a standard dose for carotid CTA in adults is 1.5 to 2.0 mL per kilogram of body weight
  • the maximum dose can be calculated using 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]


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Contrast media hypersensitivity reaction

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

    • most of the reactions are not immune-mediated (do not involve antibodies) and are dose-independent = these effects should be referred to as contrast media hypersensitivity reactions
    • symptoms and treatment are the same as for an 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 common after intravascular administration
  • history of a previous reaction to iodinated contrast media (200-fold increased risk)
    • get details of previous reactions and consider alternative imaging methods (e.g., non-contrasted study, ultrasound, MRI)
  • hyperthyroidism
  • family history of hypersensitivity reaction to iodinated contrast media (14-fold risk)
  • allergic diseases, including asthma (6-10x increased risk)
    • not a contraindication – the risk of severe reactions is low with non-ionic and low-osmolality iodinated contrast media
  • history of multiple allergies
    • not a contraindication; get a 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 adverse reaction
  • usually manifests > 1 hour (up to a week) after contrast administration
  • most commonly presents as a mild to 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
  • routine screening of thyroid function is generally not feasible in the general population
  • in patients with a history of hyperthyroidism, thyrotoxicosis, or thyroiditis, administration of an iodinated contrast may 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 interfering with thyroid scintigraphy diagnosis for more than 2 weeks
  • if thyroid cancer is suspected, avoid an iodinated contrast agent because subsequent treatment with radioactive iodine would not be possible (for up to six months after the administration)
Patient with pheochromocytoma
  • administration of an iodinated contrast agent may cause a hypertensive crisis; premedication with alpha-blockers is recommended to prevent this complication
  • choose another imaging method (MRI) if possible
Contrast media extravasation
  • symptoms may vary from local pain and tenderness up to skin ulcers, necrosis, or even acute compartment syndrome
  • small extravasations result in minimal swelling or erythema and require no specific therapy; for larger volumes, cold compression with an ice pack and elevation of the affected extremity is recommended
    • stop the contrast agent infusion and notify the radiologist
    • attempted aspiration of the extravasation is not effective
  • monitor the patient for several days until signs and symptoms resolve
  • critical symptoms (increasing swelling and pain, ulceration, altered tissue perfusion) require surgical intervention

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Administration of iodinated contrast agents
link: https://www.stroke-manual.com/administration-of-iodine-contrast-agents/