Clinical Features

  • Examples of iodinated radiocontrast media (RCM), typically used for X-ray, CT studies
    • High osmolar (ionic)
      • Diatrizoate (Hypaque 50, Gastrografin)
      • Metrizoate (Isopaque 370)
      • Ioxaglate (Hexabrix)
      • Ioxitalamate (Telebrix)
    • Low osmolar (non-ionic)
      • Iopamidol (Isovue 370)
      • Iohexol (Omnipaque 350)
      • Ioxilan (Oxilan 350)
      • Iopromide (Ultravist 370)
      • Iodixanol (Visipaque 320)


Mechanisms of Adverse Reactions to RCM
Acute
Anaphylactoid
  • Likely related to osmolarity, which is known to augment basophil and mast cell histamine release. Complement activation may account for some reactions.
  • Occur in 1-3% of patients who receive ionic RCM (0.22% of these reactions are severe life-threatening) and <0.5% of patients who receive nonionic (0.04% severe life-threatening)
IgE-mediated
  • Much less common than anaphylactoid reactions
  • May play a role in severe reactions to non-ionic contrast media
Delayed
?Cell-mediated
  • Defined as reactions occurring 1 hour to 1 week after RCM, occur in approximately 1-3% of patients.
  • Most are mild, self-limited cutaneous eruptions (often maculopapular) that may be T-cell mediated, although more serious reactions, such as SJS, TEN, and DRESS have been described.
Chemotoxic
  • Related to the chemical properties of the contrast agent, and they are dose and concentration dependent. They tend to occur in medically unstable patients who are debilitated.
  • For example cardiotoxicity, neurotoxicity, and nephrotoxicity


Risk Factors

Risk factors for anaphylactoid reaction onset/severity to RCM include:
  • Female sex
  • Asthma
  • Atopy
  • History of previous reactions to RCM
  • Beta-blocker and/or the presence of cardiovascular conditions
  • Seafood allergy and/or iodine sensitivity is NOT a risk factor
    • This includes patients with a history of contact dermatitis to iodine-containing solutions (e.g. povidone iodine)



Management


General Approach for Anaphylactoid Reactions

  • Management of a patient who requires RCM and has had a prior anaphylactoid reaction to RCM includes:
    1. Determine whether the study is essential
    2. Determine that the patient understands the risks
    3. Ensure proper hydration
    4. Use a nonionic, iso-osmolar RCM, especially in high-risk patients (asthmatic patients, patients taking beta-blockers, and those with cardiovascular disease)
      • If possible, infuse as little RCM agent at the slowest rate as feasible to get the desired image
    5. Use a pretreatment regimen that has been documented to be successful in preventing most reactions:

Elective Premedication

  • For readministration of RCM to prior anaphylactoid reactors, premedication with corticosteroid and antihstamines significantly reduces (5-10 fold), but does not eliminate, the risk of anaphylactoid reaction

Time before procedure (hours))
Drug
Dose------------------------
Note
-13
Prednisone
1 mg/Kg PO
Up to 50 mg
  • May substitute hydrocortisone 200 mg IV if unable to take PO
-7
Prednisone
1 mg/Kg PO
Up to 50 mg
  • May substitute hydrocortisone 200 mg IV if unable to take PO
-1
Prednisone
1 mg/Kg PO
Up to 50 mg
  • May substitute hydrocortisone 200 mg IV if unable to take PO
-1
Diphenhydramine---
1 mg/Kg PO/IM
Up to 50 mg

-1 (optional)
Ranitidine
1-2 mg/Kg PO/IM
Up to 150 mg--------
  • H2 receptor antagonists are beneficial in the treatment of anaphylaxis
  • When the addition of H2 receptor antagonists 1 hour before RCM was studied, a modest increase in reaction rate was observed
-1 (optional)
Albuterol or Ephedrine-_-
4 mg or 25 mg PO
  • These agents may not be favorable from a risk-benefit standpoint in patients with cardiovascular disease

  • Alternative premedication protocol (Lieberman): Prednisone 50 mg PO at -12 hours, -6 hours, and -30 minutes prior to the RCM + diphenhydramine 50 mg PO -30 minutes prior to RCM
  • Alternative protocol (ACR): methylprednisolone 32 mg PO at -12 hours and -2 hours prior to RCM +/- Diphenhydramine 50 mg PO -1 hour prior to RCM
  • For anaphylactoid reactions despite premedication, consider graded challenge or desensitization
    • Lieberman: Administer serial dilutions of RCM in saline, beginning with a 1:1000 dilution at an initial dose of 0.2 mL. Double the dose every 10 minutes, progressing through the 1:100, 1:10, and finally, the full strength preparation. Ten minutes after you have administered 1 mL of the full strength, you could proceed with the desired dose of radiocontrast.
    • Gandhi:
      Visipaque RCM desensitization protocol.png



Emergency Premedication (ACR)


In decreasing order of desirability:
  • Methylprednisolone 40 mg or hydrocortisone 200 mg IV q4h until RCM + diphenhydramine 50 mg IV -1 hour prior to RCM
  • Dexamethasone 7.5 mg or betamethasone 6 mg IV q4h until RCM + diphenhydramine 50 mg IV -1 hour prior to RCM; recommended for patients with known allergy to methylprednisolone, aspirin or NSAIDs, especially if asthmatic
  • Diphenhydramine 50 mg IV alone (e.g. if contrast study to be done in <4 hours)


Skin Testing

IgE-mediated reactions
  • In IgE-mediated reactions, negative skin testing may predict which RCM agents can be given safely
  • For example, SPT to undiluted agent followed by intradermal at 1000 and 10 fold dilutions has been reported, and readministration of agents causing positive skin tests is avoided
Delayed reactions
  • Delayed reading of intradermals (at 24 h) and patch testing (at 24, 48, 72 h) with contrast media has been reported
  • Patients with delayed reactions to a RCM agent are likely to have positive delayed skin tests to other agents that are similar in chemical structure
  • Negative delayed skin testing may predict which RCM agents can be given safely


Note
  • Reactions to RCM can occur when administered via nonvascular routes (e.g. during histosalpingograms, myelograms, intraarticular injections, and via other routes of administration). A patient receiving nonvascular RCM with a history of reaction to RCM should be treated using the same protocols outlined above.




Gadolinium

  • Gadolinium (Gd) contrast agents are used to enhance MRI images, can be divided into 3 categories:
    • Non-ionic linear (open-chain): Omniscan, Optimark
    • Ionic linear (open-chain): Magnevist, MultiHance, Eovist, Ablavar
    • Macrocyclic: ProHance, Dotarem, Gadovist

  • Serious adverse reactions are rare (<1%)
    • Increase risk for nephrogenic systemic fibrosis in patients with impaired renal function (contraindicated in chronic, severe kidney disease or acute kidney injury)
    • Hypersensitivity reactions are rare and it is unclear whether the reaction are primarily IgE-mediated or anaphylactoid
      • Positive skin testing (SPT and ID) may suggest IgE-mediated reaction
        • Contrast agent used full-strength (undiluted) for ID testing may result in irritant reaction
      • Sensitivity may be to a specific Gd contrast agent, other agents may be safe if skin testing negative

  • No published pre-treatment protocols available specifically for Gd contrast agent reactions



References