Iodinated contrast media


Iodinated radiographic contrast media are widely used. Reactions from intravascular injection are usually mild and self-treated. Radiographic contrast media can be divided into 4 categories:

Ionic monomers (highest osmotoxicity: ratio 1.5; highest carboxyl group toxicity)

Diatrizoate, iothalamate, ioxythalamate, iodamide, metrizoate.

Ionic dimers (lower osmotoxicity: ratio 3; lower carboxyl group toxicity)

Ioxaglate.

Non ionic monomers (same osmotoxicity as ionic dimers; no carboxyl group toxicity).

4 hydroxyl groups: metrizamide, iopromide.

5 hydroxyl groups: iopentol, iopamidol, iomeprol, ioxitol.

6 hydroxyl groups: iohexol, ioversol.

Non ionic dimers (lowest osmotoxicity; no carboxyl group toxicity).

9 hydroxyl groups: iodixanol.

12 hydroxyl groups: iotrolan.

Incidence
Acute reaction rates:

High osmolarity contrast media (HOCM):

  • Mild: 2.5 to 12.66%
     
  • Moderate: 0.22 to 1.2%
     
  • Severe: 0.04 to 0.4%

Low osmolarity contrast media:

  • Mild: 0.58 to 3.13%
     
  • Moderate: 0.04 to 0.11%
     
  • Severe: 0 to 0.016%.

Risk of repeated reaction: 17 to 35%.

Death
 
HOCM: 1/10931 to 1/117000.
 
LOCM: 0 to 1/168363.
 
Delayed reactions: 5 to 30% with ionic monomers.
                            5 to 15% with non-ionic monomers.

No significant association with immediate reactions, allergy, previous adverse reaction to contrast media.
 
May be over estimated due to false delayed adverse reactions resulting from clinical methodology (questionnaire).
 
Risk factors
  • Asthma

    relative risk of any reaction: 1.2 to 2.5
    relative risk of severe reaction: 5.1 to 8.4

    A patient with peak expiratory flow less than 400 l/ min 10 minutes before injection runs a 3.8 times higher risk of developing an adverse reaction to intravascular injection of contrast media.
  • Food or medication allergies:

    relative risk of any reaction: 1.6 to 3
    relative risk of severe reaction: 2.3 to 3.2
     
  • Previous contrast reaction:

    relative risk of any reaction: 3.3 to 6.9
    relative risk of severe reaction: 4.5 to 10.9
     
  • Atopy
     
  • Concomitant use of interleukin 2 increases incidence and severity of delayed reactions (fever, chills, rigors, flushing, dizziness, hypotension).
     
  • Beta-adrenergic blockers: relative risk 2.7
     
  • Female gender is associated with greater risk of anaphylactoid reactions and severe anaphylactoid reactions
     
  • Cardiac diseases
     
  • Sea-food allergy or povidone-iodine allergy are not risk factors.
Clinical manifestations
Differentiate from other cardiac or non cardiac manifestations: vasovagal response, cardiogenic shock, myocardial infarction, cardiac tamponade, cardiac rupture, hypovolemia, sepsis or other drug intolerance.
 
Minor reactions
 
Pruritus, urticaria (limited), erythema: no treatment.
 
Moderate reactions
 
Urticaria (diffuse), angioedema, laryngeal edema, bronchospasm: treatment.
 
Severe reactions
 
Cardiovascular shock, respiratory arrest, cardiac arrest: hospitalization.
 
Differentiate from non-idiosyncratic manifestations: warmth, metallic taste in the mouth, nausea, vomiting, contrast-induced renal failure.
 
Delayed reactions (at least 30 minutes after contrast media injection).
 
Flu-like syndrome: fatigue, weakness, upper respiratory tract congestion, fever, chills, nausea, vomiting, diarrhea, abdominal pain, rash, dizziness, headache.
 
Diagnostic methods
A few reports state that anaphylactoid reactions could be IgE-mediated: one case with positive intradermal reaction to meglumine and sodium diatrizoate (1/100) and positive human basophil degranulation test (HBDT).
 
Mechanisms
Not fully known, but hyperosmolarity is crucial.
 
The chemotoxicity, osmotoxicity and iontoxicity of contrast media influence cell membranes of blood cells, platelets, endothelial cells and mast cells leading to release of vasoactive substances (histamine, leukotrienes, prostaglandines) and structural changes in molecules of the complement, coagulation, fibrinolytic, or kinin system leading to activation and creation of bradykinin, anaphylatoxins.
 
Antigen-antibody interaction, if any is exceptional.
 
The role of 2 mercaptobenzothiazole (MBT) used in the manufacture of rubber and present in disposable plastic syringes has seldom been advocated.
 
Management
Universal premedication with corticosteroids:
 
Methylprednisolone 32 mg 12 h and 2 h before injection of conventional ionic contrast media decreases the frequency of all reactions from 9% to 6.4% and of severe reactions requiring treatment from 2% to 1.2%.
 
Patients with history of prior reactions to contrast media
 
1°- Use a low osmolarity RCM.
 
2°- Prednisone: 50 mg 13 hours, 7 hours and 1 hour before the procedure.
 
3°- Diphenydramine: 50 mg intramuscular 1 hour before the procedure.
 
4°- Ephedrine: 25 mg p.o 1 hour before the procedure (optional).
 
1°+2°+3°: 0.7% reactions 1°+2°+3°+4°: 0% reaction
 
Use of anti H2 histamine is optional and controversial.
 
Hydroxyzine 100 mg p.o 12 hours before intravenous injection of the ionic dimer ioxaglate decreases the rate of
reactions from 12.5% to 1% in low-risk patients.
 
Emergency pre-treatment in previous reactors:
 
Intravenous hydrocortisone 100-250 mg q 4 hours until completion of the procedure.
 
Diphenydramine p.o, i.m, i.v, 1 hour before the procedure.
 
Iopamidol causes fewer allergic-type adverse events but more flushing than ioxaglate in patients with asthma or atopic disease.
 
Pre-testing with an intravenous injection of a small amount of contrast media is not useful in predicting severe reactions to ionic or non-ionic contrast media.
 
In patients at risk of anaphylactoid reactions to radiographic contrast media
 
1°- Evaluate the necessity of a procedure requiring RCM.
 
2°- Administration of a LOCM to patients with prior severe anaphylactoid reactions to HOCM.
 
3°- Have emergency equipment available.
 
4°- Use a pre-treatment protocol.
 
5°- Discontinue beta-blockers if possible

References

  1. Cohan R.H, Ellis J.H, "Iodinated contrast material in uroradiology. Choice of agent and management of complications", Urol. Clin. North. Am., 1997; 24 (3): 471-91 
  2. Simon M.R, "Allergic-type adverse reactions to low-osmolarity contrast media in patients with a history of allergy or asthma", Invest. Radiol., 1995; 30 (5): 285-90 
  3. Lang D.M, Alpern M.B, Visintainer P.F, Smith S.T, "Gender risk for anaphylactoid reaction to radiographic contrast media", J. Allergy. Clin. Immunol., 1995; 95 (4): 813-7 
  4. Almen T, "The etiology of contrast medium reactions", Invest. Radiol., 1994; 29 (S1): S37-45 
  5. Bertrand P.R, Soyer P.M, Rouleau P.J, Alison D.P, Billardon M.J, "Comparative randomized double-blind study of hydroxyzine versus placebo as premedication before injection of iodinated contrast media", Radiology., 1992; 184 (2): 383-4
  6. Greenberger P.A, Patterson R, "The prevention of immediate generalized reactions to radiocontrast media in high-risk patients", J. Allergy. Clin. Immunol., 1991; 87 (4): 867-72
  7. Katayama H, Yamagushi K, Kozuka T, Takashima T, Seez P, Matsuura K, "Adverse reactions to ionic and non ionic contrast media. A report from the Japanese committee on the safety of contrast media", Radiology, 1990; 175: 621-8 
  8. Lasser E.C, Berry C.C, Talner L.B, et al., "Pretreatment with corticosteroids to alleviate reactions to intravascular contrast material", N. Eng. J. Med., 1987; 317: 245-9

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.