SERIOUS ADVERSE REACTIONS TO CONTRAST MEDIA

A ZAIEM, I AOUINTI, R DAGHFOUS, M LAKHAL, S ELAIDLINational Centre of Pharmacovigilance, Tunis

VR6

INTRODUCTION

Contrast Media (CM) are generally well tolerated.

Adverse reaction reported with CM are in most cases mild toxic reactions such as heat sensation, nausea and vomiting.

Although serious adverse reactions to CM are rare, these reactions are exceptionally notified to pharmacovigilance authorities.

OBJECTIVE

The aim of this study was to examine the features of serious adverse reactions associated with CM and reported to the Tunisian PharmacoVigilance Centre.

MATERIALS and METHODSA 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.

RESULTSFive 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.

Case n° 1A 18-year-old maleMedical history of Hodgkin diseaseA CT scan in January 2009During the injection of CM (ioxitalamate) pain,

burning sensation at injection site and a tumefaction of hand and forearm

The radiography of left hand was normalA veinous echodoppler showed a thrombosis of

superficial cephalic veinThe treatment: sulodexide, antalgic and anti-

inflammatory drugsThe outcome: favorable in 20 days

Case n°2:A 54-year-old maleMedical history of unprecised urological diseaseA uro CT scan in November 2008At the start of injection of CM (ioxitalamate) pain,

erythema and induration at injection site on the pathway of the vein.

The treatment was not precised.The outcome favorable in one week.

Case n°3A 65-year-old femaleMedical 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.

Case n°4A 55-year-old femaleMedical history of allergy to penicillin and allergic

rhinitisA brain scan for headache in 2008.During injection of CM (ioxitalamate) lost of

consciousness for few minutes. No cutaneous eruption, nor hemodynamic troubles.

Case n°5A 18-year-old maleTreated for scoliosis since january 2010 by anti

inflammatory drugsA scopy with injection of CM (iohexol) of lumbar

vertebrae in order to infiltrate cortivazol in december 2010.

Ten minutes later generalized erythema and pruritus.

Treatment: corticotherapy.The outcome favorable in 15 minutes.

Sexe Age exploration CM Reaction Delay

Case 1 M 18 CT scan Ioxitalamate Thrombophlebitis During injection

Case 2 M 54 Uro CT scan Ioxitalamate Thrombophlebitis During injection

Case 3 F 65 Intravenous urography

Ioxitalamate Anaphylactic shock Few minutes after injection

Case 4 F 55 Brain scan Ioxitalamate Loss of consciousness During injection

Case 5 M 18 Scopy of lumbar vertebrae

Iohexol Generalized erythema and pruritus

Ten minutes after injection

DiscussionCM 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 osmolar CM,

Non ionic dimers iso osmolar CM.

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 CM0.7% 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 material0.02% to 0.04% with nonionic contrast material

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.

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.

Conclusion

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

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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.

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