Olivier Clement is Professor of Radiology at the Hôpital Europeen Georges Pompidou in Paris. He is involved in research on new contrast agents for functional and cellular imaging (Insem U 494, School of Medicine Necker, Paris). He is the chairman of a working group on contrast agents of the French Society of Radiology, and of the European Association of Radiology. He launched a nationwide study in France on the pathophysiology of anaphylactic reactions to iodinated contrast agents.

Olivier Clement
Department of Radiology, Hôpital Européen Georges Pompidou, Paris, France

Key words: contrast media; allergy; anaphylaxis; life support; adrenaline

This work has been presented at the European Congress of Radiology 2002 and 2003.

Address for correspondence
Pr Olivier CLEMENT
Service de Radiologie
Hôpital Européen Georges Pompidou
20 rue LEBLANC
75908 PARIS cedex 15
Tel: + 33 1 56 09 38 22 or 38 51
Fax: + 33 1 56 09 38 50
Email: clement@necker.fr

The following topics are covered in detail in the article:
1) Diagnosis
2) General management
3) Cutaneous symptoms
4) Respiratory symptoms
5) Generalized anaphylactoid reaction
6) Other systemic reactions
7) Before the reaction
8) After the reaction

1 DIAGNOSIS
Adverse reactions to contrast agents can be:
● Immediate (<1 hour) or ● Non-allergy-like   - Cardiovascular    (vagal reaction, angina, pulmonary oedema)   - Renal    (contrast-induced nephropathy, acute renal failure;     semi-delayed)   - Neurological    (seizure owing to severe hypotension or intrathecal    injection) ● Allergy-like or anaphylactoid   - Diagnosis (Table 1)   - Cutaneous (erythema, urticaria, angio-oedema, pruritis)   - Haemodynamic (hypotension, tachycardia)   - Respiratory (laryngeal oedema, bronchospasm,     wheezing)   - Gastrointestinal (vomiting, diarrhoea)   - Pathophysiology   - Non-specific histamine release   - Type 1 allergy: IgE-mediated anaphylaxis	● Delayed (>1 hour to 1 week)

2 GENERAL MANAGEMENT

Be calm, diagnose before you treat, eliminate hypoglycaemia ALWAYS ● Stop injection/infusion ● Call for help ● Note time of reaction, product/concentration/volume injected ● Take pulse (bradycardia=vagal, tachycardia=anaphylactic shock) ● Take blood pressure ● Check IV lines ● Give oxygen (good in all cases: asthma, angina, vasovagal, anaphylaxis…)

3 CUTANEOUS SYMPTOMS
● URTICARIA, with a few scattered hives Do nothing; watch the patient until resolves	● URTICARIA, severe, extensive - Diphenhydramine IV, IM (30 mg adults, 1.25    mg/kg children), or - Cimetidine (300 mg diluted in 20 mL IV adults,   5–10 mg/kg for children), or - Ranitidine 50 mg diluted in 20 mL IV
● CONSIDER ADRENALINE IF DETERIORATION WITH HYPOTENSION OR BRONCHOSPASM

4 RESPIRATORY SYMPTOMS
Oxygen : 6–10 L/min
● LARYNGEAL ANGIO-OEDEMA Diagnosis: inspiratory stridor - Epinephrine (adrenaline): - 0.3 mg SC up to 1 mg - 0.1 mg IV repeat as necessary (see 5    dilution/ titration) - Steroids: - Methylprednisolone 50 mg IV - or prednisolone 250 mg IV	● BRONCHOSPASM Diagnosis: expiratory wheezes - β2-agonist dose inhaler:   2–3 deep inhalations - Steroids: - Methylprednisolone 50 mg IV - or prednisolone 250 mg IV - Epinephrine (adrenaline) : - 0.3 mg SC up to 1 mg - 0.1 mg IV repeat as necessary   (see 5 dilution/titration)

5 GENERALIZED ANAPHYLACTOID REACTION

Oxygen : 6 –10 L/min

Diagnosis: hypotension (<80 mm Hg, tachycardia >100/min, dyspnoea, cutaneous signs, diarrhoea, vomiting) SUPINE POSITION, ELEVATED LEGS EPINEPHRINE (ADRENALINE) DILUTION AND TITRATION ● Effect and dose of epinephrine (adrenaline) depend on the patient, and must     be tested in the patient.     A very large range of dose might be needed for the same effect. ● Dilution 1/10 (1 mg epinephrine plus 9 mL saline) ● Do not inject epinephrine undiluted IV except during cardiac arrest ● Injection 1 mL by 1 mL IV of the diluted solution every few minutes until an effect occurs ● Short plasma half-life: repeat the doses every 3 min based on the clinical symptoms VOLUME SUBSTITUTION - Crystalloids (saline or Ringer’s) 30 mL/kg IV, then    - Colloids 30 mL/kg IV

6 OTHER SYSTEMIC REACTIONS

● VASOVAGAL REACTION Oxygen : 6–10 L/min - Volume substitution, crystalloids (saline or Ringer’s solution) 30 mL/kg IV - Atropine 0.5–1 mg IV repeated if necessary to 3 mg total (adult), 0.02 mg/kg IV     up to 2 mg total (children) If no effect, treat as an anaphylactic shock ● CARDIAC ARREST Oxygen : 6–10 L/min    - Cardiopulmonary resuscitation    - Epinephrine (adrenaline) 1 mg IV repeated every 3 min    - Volume substitution ● ANGINA Oxygen : 6–10 L/min    - Nitroglycerin spray or sublingual ● PULMONARY OEDEMA Oxygen : 6–10 L/min    - Furosemide 20–40 mg IV ● SEIZURE Oxygen : 6–10 L/min    - Diazepam 5 mg, IV ● HYPOGLYCAEMIA (symptoms of confusion)    - Glucose IV, PO

7 BEFORE THE REACTION : be prepared

● Have resuscitation trolley ready with valid drugs and equipment ● Provide information for personnel ● Keep phone numbers posted ● Exercises, continuing medical education

8 AFTER THE REACTION : investigate

● Blood test for measurement of histamine and tryptase immediately after the reaction     (proves anaphylaxis compared with other mechanisms) ● Follow up the patient for 12–24 hours ● Specialised allergological consultation 4–8 weeks later to prove potential allergy to     one specific contrast or to try to explain the reaction that occurred

Grade	CUTANEOUS & MUCOSAL	GASTROINTESTINAL	RESPIRATORY	CARDIOVASCULAR
I	Erythema Urticaria Facial oedema Mucosal oedema
II	“ “ “	Nausea important AFTER the injection	Cough Dyspnoea	Tachycardia >30 % Hypotension (drop in systole >30%)
III	“ “ “	Vomiting and/or diarrhoea	Bronchospasm Cyanosis	Shock (BP syst<80 and HR >100 if no β-blockers)
IV	“ “ “	“ “ “	Respiratory arrest	Cardiovascular arrest

REFERENCES
http://www.resus.org.uk/siteindx.htm
http://circ.ahajournals.org/content/vol102/suppl_1/
http//www.sfar.org