Adverse Reactions to Contrast Media

Ri 陳達慶

Articles

Acute serious and fatal reactions to contrast media: our current understanding

S K Morcos, FRCS, FRCR British Journal of Radiology (2005) 78, 686-693

Adverse Reactions to Intravenous Iodinated Contrast Media: An Update

Saravanan Namasivayam MD, DNB, DHA, Mannudeep K. Kalra MD, DNB, William E. Torres MD and William C. Small MD, PhD

Current Problems in Diagnostic Radiology Volume 35, Issue 4 , July-August 2006, Pages 164-169

Introduction

unpredictable and not dose related CM particles absorbed into the circulation all the features of anaphylaxis but IgE negative in most cases developed within 5–30 min after exposure to

CM may present as generalized skin reactions,

airway obstruction, angioedema or cardiovascular collapse

intermediate risk for anaphylaxis with CM

Prevalence of life threatening and fatal reactions to contrast media

severe and very severe reactions (IV push of CM) 0.22% and 0.04% after high-osmolar contrast media (HOCM) 0.04% and 0.004% after low-osmolar contrast media (LOCM) However no difference in fatal reactions (1:170 000) UK & USA(FDA) (per million examinations) high with low osmolar

CM 194 vs 44 for all reactions 37 vs 11 for severe reactions 3.9 vs 2.1 for fatal reactions. high osmolar agents V.S.ioxaglate (a low osmolar ionic dimer) total reactions 194 vs 143 severe reactions 37 vs 34 fatal reactions 3.9 vs 6.4 low osmolar non ionic CM is the best, besides no definite reductio

n in fatal reactions,

Risk factors 1. A history of previous severe adverse reaction to a contr

ast agent 6 (both ionic and non-ionic CM) 2. Asthma 6~10 3. A strong history of allergic reactions to different substa

nces (hay fever….) 4. Treated with ß-adrenergic blockers and interleukin-2 (I

L-2) acute adverse reactions to CM. (including the ophthalmic preparations)

5. Iodinated CM 3 6. Female <-> the fatality rate :men with old age?! 7. Race 8. Malignant tumours an increase in histamine release

Pre-testing with an intravenous injection of a small amount of CM is not useful

High awareness !!

Table 1. European Society of Urogenital Radiology (ESUR) guidelines on prevention of generalized co

ntrast medium reactions in adults

Pathophysiology of life threatening/fatal reactions to contrast media

adverse reactions to drugs type B reactions, not dose dependent and unpredictable

Aronson and Ferner: a new classification (DoTS) based on dose relatedness (Do), timing (T) and patient susceptibility (S)

drug (pharmacology and the dose dependence of its effects) the properties of the reaction (time course of its appearance a

nd its severity) properties of the individual (the genetic, pathological and other

biological differences that confer susceptibility)

Do-hyper susceptibility; T – first dose; S – not understood.

Pathophysiology Type 1 hypersensitivity reaction (anaphylaxis) --- lack of co

nsistency in demonstrating antibodies to CM Within minutes Chemotactic, vasoactive and spasmogenic compounds. leuko

trienes, prostaglandins, enzymes basophils and mast cells degranulation Histamine pri

mary mediator ; intense immediate manifestations. (be reproduced by histamine infusion)

vasodilatation, increasing vascular permeability edema contraction of smooth muscle cells bronchospasm ; incr

easing mucus secretion of airways recruit WBC additional waves of cytokines direct effect of CM particles on these cells non ionic monomers low levels of histamine release Hyperosmolarity yes Increasing the size and complexity of the molecule enhanc

e the release of histamine

Pathophysiology--2

Activation of factor XII (Hageman factor) kinin system production of bradykinin induce vasodilatation, bronchospasm and increase vascular permeability.

Bradykinin arachidonic acid cyclooxygenase and lipooxygenase pathways synthesis of PGs & LTs

Patients who are asthmatic or allergic increased concentration of factor XII products

CM DOESN’T act as happens (non-reactive chemically) p-I concept drugs may directly activate T cells via receptors that

can interact with the drug. unlikely T cell VS. acute life threatening CM not clear

IgE antibodies? Complement system (C3a, C4a and C5a) ? no significant differe

nce

Diagnosis of serious or fatal reaction to contrast media Histamine --- basophils and mast cells, tryptase---mast cells Tryptase : 1–2 h after the reaction (not greater than 6 h) Only very high concentrations of serum tryptase should be reg

arded specific Histamine: 10 min to 1 h after the reaction Methylhistamine, the main metabolite of histamine measu

red in urine Specific IgE antibodies reliable drug RAST tests are not w

idely available Positive intradermal tests some severe reaction to CM it is advisable to measure serum tryptase routinely in severe o

r fatal patients (AMI or severe vasovagal attack may develop during examinations)

Post-mortem findings --- High level of seum tryptase, macroscopic findings including pulmonary oedema, signs of asthma (mucous plugging and/or hyperinflated lungs), petechial haemorrhages and pharyngeal/laryngeal oedema

Prevention of acute reactions to contrast media Explained to the patient & the resuscitation team

Non-iodinated CM: 1. carbon dioxide (CO2) --- nausea, abdominal and leg pain may be obs

erved with its administration2. gadolinium based CM--- intravascular, no above 0.3 mmol kg–1 body

weight induce nephrotoxicity (not sure) Non-ionic contrast media (sure)

The prophylactic use of corticosteroids --- mechanism unclear Antihistamines (H1 and H2) and ephedrine --- (not sure) Corticosteroids complex with the cytoplasmic receptormigrate int

o the cell nucleus activate DNA dependent RNA synthesis accelerated formation of specific enzymes inhibitors take time

1. significant elevation in functional C1-esterase inhibitor levels, 12 h after ; inhibits the activated form of factor XII2. Decreased arachidonic acid from cell membranes production of PGs &LTs (not sure)

Prevention of acute reactions to contrast media-2

fatality may still occur in patients who received pre-medication and low osmolar CM

Prompt recognition and treatment of adverse side effects to CM invaluable

never be left alone for at least 20 min after CM injection the venous access

Emergency administration of contrast media in high-risk patients

1. pre-treatment with hydrocortisone, 200 mg intravenously, immediately, and every 4 h until the procedure is completed

2. diphenhydramine, 50 mg intravenously before the procedure 3. low osmolar non-ionic CM

Treatment of acute severe reactions to contrast media Important first-line management 1. Adequate airway, oxygen supplementation, (adrenaline use)2. IV physiological fluids, measuring BP &HR (most effective treatment for hypot

ension) 3. Adrenaline effective drug increases BP, reverses peripheral vasodilatation,

decreases angioedema and urticaria, reverses bronchoconstriction, and produces positive inotropic and chronotropic cardiac effects (avoided in the pregnant patient)

Only one concentration (1:1000) IM of 0.5 ml of 1:1000 adrenaline preparation

IV IS NOT GOOD requires careful ECG monitoring (arrhythmia) Antihistamine H1 receptor blockers reduce symptoms from skin reactions

slow onset of action, and they cannot block “ ALREADY” events H2-antagonists not essential IV injection of high-dose corticosteroids an immediate stabilizing effect

on the cell membrane second-line treatment. reducing delayed recurrent symptoms

Inhaled ß-2-adrenergic agonists (albuterol, metaproterenol and terbutaline) bronchodilating

Atropine blocks vagal stimulation of the cardiac conduction system. Large doses of aptropine (0.6–1.0 mg) are indicated 

Table 2. First-line emergency drugs and instruments that should be in the room where contrast medium is injected

Table 3. Simple guidelines for first-line treatment

of acute severe reactions to contrast media

Thanks for your attention!