Immediate Reactions Following Iodinated Contrast Media Injection: a Study of 38 Cases
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European Journal of Radiology 77 (2011) 495–501 Contents lists available at ScienceDirect European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad Immediate reactions following iodinated contrast media injection: A study of 38 cases Pascale Dewachter a,∗, Dominique Laroche b,1, Claudie Mouton-Faivre c,2, Evelyne Bloch-Morot d,3, Jean-Pierre Cercueil e,4, Liliane Metge f,5, Marie-France Carette g,6, Marie-Claude Vergnaud h,7, Olivier Clément i,8 a Service d’Anesthésie-Réanimation Chirurgicale & SAMU de Paris, Hôpital Necker-Enfants Malades, AP-HP, Université Paris-Descartes, 149 Rue de Sèvres, 75015 Paris, France b Service de Biophysique, Centre Hospitalier Universitaire, Avenue de la Côte de Nacre, Caen, France c Pôle d’Anesthésie-Réanimation Chirurgicale, Centre Hospitalier Universitaire-Hôpital Central, Avenue du Maréchal de Lattre de Tassigny, Nancy, France d Service de Médecine Interne, Hôpital Européen Georges Pompidou, 20 Rue Leblanc, Paris, France e Département d’Imagerie Medicale, Centre Hospitalier Universitaire, Hôpital du Bocage, 2, Boulevard du Maréchal de Lattre de Tassigny, Dijon, France f Département d’Imagerie Médicale, Centre Hospitalier Universitaire Caremeau, Place du Pr Robert Debré, Nîmes, France g Service de Radiologie, Hôpital Tenon, 4 Rue de la Chine, Paris, France h Service de Médecine Polyvalente, Centre Hospitalier Universitaire, Avenue de la Côte de Nacre, Caen, France i Service de Radiologie, Hôpital Européen Georges Pompidou, AP-HP, Université Paris Descartes, 20 Rue Leblanc, Paris, France article info abstract Article history: Objectives: To investigate the pathomechanisms involved in cases of immediate hypersensitivity reactions Received 2 August 2009 occurring after the administration of iodinated contrast media. Accepted 17 September 2009 Materials and methods: Patients having presented clinical signs of immediate hypersensitivity suggesting allergy after iodinated contrast medium were investigated. Histamine and tryptase concentrations were Keywords: measured, and/or skin tests were performed. Patients with positive skin tests to the culprit contrast agent Anaphylaxis were classified as IgE-mediated allergic hypersensitivity (Group I) and patients with negative skin tests Contrast media as non-allergic hypersensitivity (Group II). Hypersensitivity Immediate Results: 38 patients were included. Most reactions appeared after non-ionic (n = 32). Reactions were more Skin tests frequently severe following ionic than non-ionic (p = 0.014). Skin testing was not performed in 11 patients. Histamine Skin tests with the culprit contrast agent were negative in 26% of the patients (Group II, n = 7) whereas Tryptase they were found positive with the contrast agent in 73% of the patients (Group I, n = 19). Latex-induced reaction was diagnosed in one patient, and was consequently excluded from the cohort. In Group I, the frequency of cross-reactivity with the other commercialized iodinated contrast media was low (7%). Cardiovascular signs were present in Group I (52.6%, n = 10), and absent in Group II (p = 0.023). Histamine and tryptase concentrations were higher in patients who had cardiovascular signs (p < 0.02). Conclusion: Immediate reactions with clinical signs suggesting allergy along with positive skin tests with the administered contrast agent confirm immediate allergic hypersensitivity (anaphylaxis) to this agent. Consequently, the culprit contrast agent should be definitely avoided as well as cross-reactive ICM in order to prevent further recurrences. © 2009 Elsevier Ireland Ltd. All rights reserved. ∗ Corresponding author. Tel.: +33 1 44 49 54 07; fax: +33 1 44 49 54 10. E-mail addresses: [email protected] (P. Dewachter), [email protected] (D. Laroche), [email protected] (C. Mouton-Faivre), [email protected] (E. Bloch-Morot), [email protected] (J.-P. Cercueil), [email protected] (L. Metge), [email protected] (M.-F. Carette), [email protected] (M.-C. Vergnaud), [email protected] (O. Clément). 1 Tel.: +33 2 31 06 47 03; fax: +33 2 31 06 51 60. 2 Tel.: +33 3 83 85 14 03; fax: +33 3 83 85 85 59. 3 Tel.: +33 1 56 09 27 92; fax: +33 1 56 09 38 45. 4 Tel.: +33 3 80 29 36 86; fax: +33 3 80 29 32 43. 5 Tel.: +33 4 66 68 33 10; fax: +33 4 66 68 38 12. 6 Tel.: +33 1 56 01 62 91; fax: +33 1 56 01 69 32. 7 Tel.: +33 2 31 06 46 79; fax: +33 2 31 06 51 92. 8 Tel.: +33 1 56 09 38 51, Fax: +33 1 56 09 38 50. 0720-048X/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2009.09.019 496 P. Dewachter et al. / European Journal of Radiology 77 (2011) 495–501 1. Introduction 2.4. Allergological assessment Anaphylaxis remains one of the rare but significant events After informed consent was obtained, skin tests (prick-tests fol- specifically related to iodinated contrast media (ICM) that can lead lowed by intradermal tests) were performed with ICM at least 4 to morbidity and mortality, even in previously healthy patients. weeks after the occurrence of the immediate reaction. Prior to skin However, patients experiencing immediate reactions in the radi- testing, cutaneous reactivity was assessed with a positive (codeine ological area are usually not explored. Thus, in the absence of phosphate 50 gmL−1) and a negative (saline solution) controls. systematic follow-up and investigation of these patients along with Prick-tests (PTs) were performed on the forearm and were con- underreporting of these reactions, the incidence of anaphylaxis sidered positive if, within 15 min of injecting the pure drug on following ICM remains currently unknown. However, immediate the forearm, a wheal equal to at least half the positive control reactions to ICM are a major concern for radiologists, even if their and larger than the negative control appeared. Intradermal tests overall frequency has probably diminished with the increasing (IDTs) were performed after PTs, on the patient’s back, by inject- use of non-ionic ICM [1]. Thus, a multidisciplinary network of ing 0.02–0.03 mL of the ICM solution at a diluted concentration radiologists, allergologists, biochemists and anesthesiologists was ranging from 1:1000 to the pure solution, raising a wheal of about created in order to collect clinical cases of documented immedi- 3 mm. The IDT was considered positive if an erythematous and pru- ate reactions following ICM. The aim of the present study was to riginous wheal, at least doubling the size of the injection wheal, identify the pathomechanisms involved during immediate reac- and surrounded by a flare, appeared within 15–20 min after the tions following ICM on the basis of definite clinical signs and injection. IDTs were performed with the culprit ICM and with allergological assessment. This evaluation included skin testing the other commercially available ICM. PTs were also performed and biochemical assessment in order to prove the diagnosis of with two standardized commercial natural rubber latex extracts anaphylaxis, identify the culprit agent and therefore to prevent (Stallergènes, Antony, France and Allerbio, Varennes-en-Argonne, recurrences. France) as recommended elsewhere [4]. 2. Materials and methods 2.5. Statistical analysis 2.1. Patients Results were expressed as mean ± SD. The Chi-square test and Fisher’s exact test were used to compare qualitative data between Patients who experienced an immediate reaction occurring groups. The Mann–Whitney rank test was used to compare quan- less than one hour following injection of ICM had biochemical titative data between groups (Statview 5.0, SAS Cary NC, USA). measurements and/or skin tests. Patients experiencing immedi- Significance was assumed when p < 0.05. ate reactions with clinical signs suggestive of allergy and positive skin tests with the culprit ICM entered Group I (IgE-mediated 3. Results allergic hypersensitivity, i.e. immunological mechanism strongly suspected) whereas those with negative skin tests entered Group II (non-allergic hypersensitivity, i.e. immunological mechanism 3.1. Total cohort characteristics excluded) [2]. Thirty-eight patients (23 female, 15 male) who had an immedi- ate reaction following ICM injection were studied between January 2.2. Data collection 2001 and December 2003 (Tables 1–3). Mean age was 47.7 ± 17.6 years (range: 13–78 years); 44.0 ± 14.7 years for women and The following data were collected: age at the time of the reac- 53.5 ± 20.5 years for men (p > 0.05). The clinical severity of the reac- tion, gender, history of asthma, atopy, drug, food or latex allergy, tion was Grade I in 15 patients, Grade II in 13 patients, Grade premedication before the injection, name of the contrast agent III in 8 patients and Grade IV in 2 patients. Cutaneous-mucous injected, onset delay between the ICM injection and the occurrence signs were present in 35 patients (urticaria = 21; angioedema = 17; of the clinical reaction, previous exposures to ICM and previous erythema = 15), cardiovascular signs in 13 (hypotension = 3; car- reaction(s) to ICM. Clinical signs were classified according to the diovascular collapse = 8; cardiac arrest = 2), respiratory signs in Ring and Messmer four-step grading severity scale [3], adapted as 12 (cough = 7, dyspnea = 8, bronchospasm = 1) and gastrointestinal follows: Grade I involves cutaneous-mucous signs, Grade II corre- signs in 4 (nausea = 3; diarrhea = 1). The precise interval between sponds to moderate clinical signs associating cutaneous-mucous, ICM injection and onset of the reaction was recorded in 27 cases, cardiovascular or respiratory signs. The cardinal sign of Grade III and was 5 min or less in 19 cases (70.4%) and between 6 and reaction is cardiovascular collapse which may be associated with 20 min in 8 cases (29.6%). The reactions occurred after non-ionic cutaneous-mucous symptoms or bronchospasm and Grade IV is ICM injection in 32 cases (84.2%) and after ionic ICM injection in 6 cardiac arrest.