SERIOUS ADVERSE REACTIONS TO CONTRAST MEDIA

1. SERIOUS ADVERSE REACTIONS TO CONTRAST MEDIA A ZAIEM, I AOUINTI, R DAGHFOUS, M LAKHAL, S ELAIDLINational Centre of Pharmacovigilance, Tunis VR6

2. INTRODUCTION • Contrast Media (CM) are generallywelltolerated. • Adverse reactionreportedwith CM are in most cases mildtoxicreactionssuch as heat sensation, nausea and vomiting. • Althoughserious adverse reactions to CM are rare, thesereactions are exceptionallynotifiedto pharmacovigilance authorities.

3. OBJECTIVE • The aim of this study wasto examine thefeatures of serious adverse reactions associated with CM and reported to the Tunisian PharmacoVigilance Centre.

4. MATERIALSand METHODS • A retrospective study assessed in the Tunisian Pharmacovigilance Centre. • All serious adverse reactions associated with contrast media were notified. • Study period: from January 2009 to December 2011. • The notifications were analyzed according to the French method of imputation. • The seriousness of the cases was evaluated according to the WHO criteria.

5. RESULTS • Five cases of serious adverse reactions associated with CM were colleged. • Three males and two females. • Age: 18 – 65 years. • Telebrix® (ioxitalamate) incriminated in four cases. • Omnipaque® (iohexol)in one case. • Two cases of hypersensitivity reaction: a generalized erythema and an anaphylactic shock. • Two cases of cardiovascular effect : thrombophlebitis. • One case of general reaction : loss of consciousness without hemodynamic troubles. • The outcome was favorable in all cases.

6. Case n° 1 • A 18-year-old male • Medical history of Hodgkin disease • A CT scan in January 2009 • During the injection of CM (ioxitalamate)  pain, burning sensation at injection site and a tumefaction of hand and forearm • The radiography of left hand was normal • A veinousechodoppler showed a thrombosis of superficial cephalic vein • The treatment: sulodexide, antalgic and anti-inflammatory drugs • The outcome: favorable in 20 days

7. Case n°2: • A 54-year-old male • Medicalhistory of unprecisedurologicaldisease • A uro CT scan in November 2008 • At the start of injection of CM (ioxitalamate) pain,erythemaand induration at injection site on the pathway of the vein. • The treatmentwas not precised. • The outcome favorable in one week.

8. Case n°3 • A 65-year-old female • Medical history of arterial hypertension, allergic rhinitis and conjunctivitis. • An intravenous urography in April 2009. • Few minutes after CM (ioxitalamate) injection  abdominal pain, nausea, vomiting and tingling of lower limbs. • Fifteen minutes later  lost of consciousness and fall of arterial pressure • The therapeutic management: oxygenotherapy, intravenous fluid, adrenaline, and corticotherapy. • The hemodynamic constants stabilized in 30 minutes. • The patient recovered in 24 hours.

9. Case n°4 • A 55-year-oldfemale • Medicalhistory of allergy to penicillin and allergicrhinitis • A brain scan for headache in 2008. • During injection of CM (ioxitalamate)  lost of consciousness for few minutes. • No cutaneouseruption, norhemodynamic troubles.

10. Case n°5 • A 18-year-old male • Treated for scoliosissincejanuary 2010 by anti inflammatorydrugs • A scopywith injection of CM (iohexol) of lumbarvertebrae in order to infiltratecortivazol in december 2010. • Ten minutes latergeneralizederythemaand pruritus. • Treatment: corticotherapy. • The outcome favorable in 15 minutes.

12. Discussion • CM are classified on the basis of their physical and chemical characteristics including osmolality, ionization in solution, and chemical structure. • Four classes are commercially available: • Ionic monomers high osmolar CM (exp: ioxitalamate), • Non ionic monomers low osmolar CM(exp: iohexol), • Ionic dimers low osmolarCM, • Non ionic dimersisoosmolarCM.

13. In our study, four cases were associated with ioxitalamate (an ionic monomer). • Ionic CM are more often involved in adverse reactions than nonionic CM especially for minor adverse effects. • The frequency of mild anaphylactic reactions ranges from • 3.8% to 12.7% in high-osmolar ionic CM • 0.7% to 3.1% in low-osmolar nonionic CM • The risk for serious or severe reactions (anaphylaxis grade 3) ranges from • 0.1% to 0.4% with ionic contrast material • 0.02% to 0.04% with nonionic contrast material

14. In our study, three cases of immediate reaction were notified without possible determination of the mechanism (allergologic explorations were not performed). • Immediate reactions happening during the hour following the CM injection are frequently in relation with a toxic mechanism (histamino release and complement activation). The immuno-allergic mechanism (IgE dependant) is rarely reported.

15. In our study, we reported two cases of thrombophlebitis associated with ioxitalamate (ionic CM). • Although CM can have anticoagulant and anti-platelet properties as cardiovascular effects, some studies focused on their possible thrombotic effects. • These effects seem to be due to endothelial injury, secretion of prothrombotic agent and platelet activation. • CM alteration of endothelial cells appears to be related to osmolatility but not to ionicity.

16. Conclusion Our study presented five cases of serious adverse reaction to contrast media which mainly occurred after ioxitalamate administration.

17. References • Dewachter P, Mouton-Faivre C, Laroche D, Clément D. Allergie immédiate aux produits de contraste iodés et prévention des réactions. Revue de Médecine Interne 2009;30:872–881. • Trcka J, Schmidt C, Seitz CS, Bröcker EB, Gross GE, Trautmann A. Anaphylaxis to Iodinated Contrast Material: Nonallergic Hypersensitivity or IgE-Mediated Allergy? AJR American journal of roentgenology 2008;190:666-70. • Clément O. Iatrogénie des produits de contraste. Journal de radiologie 2006;86:567-72. • Esplugas E, Cequier A, Gomez-Hospital JA, Del Blanco BG, Jara F. Comparative Tolerability of Contrast Media Used for Coronary Interventions. Drug Safety 2002; 25:1079-1098.

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