Adverse Reactions to Contrast Media

1
Adverse Reactions to Contrast Media

• Ri ???

2
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

3
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 530 min after exposure to CM
• may present as generalized skin reactions, airway
  obstruction, angioedema or cardiovascular
  collapse
• intermediate risk for anaphylaxis with CM

4
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
  (1170 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 reduction in fatal reactions,

5
Risk factors

• 1. A history of previous severe adverse reaction
  to a contrast agent ? 6 (both ionic and non-ionic
  CM)
• 2. Asthma ?610
• 3. A strong history of allergic reactions to
  different substances (hay fever.)
• 4. Treated with ß-adrenergic blockers and
  interleukin-2 (IL-2) ? acute adverse reactions to
  CM. (including the ophthalmic preparations)
• 5. Iodinated CM ? 3
• 6. Female lt-gt 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 !!

6
Table 1. European Society of Urogenital Radiology
(ESUR) guidelines on prevention of generalized
contrast medium reactions in adults
7
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 and 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.

8
Pathophysiology

• Type 1 hypersensitivity reaction (anaphylaxis)
  --- lack of consistency in demonstrating
  antibodies to CM
• Within minutes
• Chemotactic, vasoactive and spasmogenic
  compounds. leukotrienes, prostaglandins, enzymes
• basophils and mast cells ? degranulation ?
  Histamine? primary mediator intense immediate
  manifestations. (be reproduced by histamine
  infusion)
• ? vasodilatation, increasing vascular
  permeability ? edema
• ? contraction of smooth muscle cells ?
  bronchospasm increasing 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 ? enhance the release of histamine

9
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 DOESNT 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 difference

10
Diagnosis of serious or fatal reaction to
contrast media

• Histamine --- basophils and mast cells,
  tryptase---mast cells
• Tryptase 12 h after the reaction (not greater
  than 6 h)
• Only very high concentrations of serum tryptase
  should be regarded specific
• Histamine 10 min to 1 h after the reaction
• Methylhistamine, the main metabolite of histamine
  ? measured in urine
• Specific IgE antibodies? reliable drug RAST tests
  are not widely available
• Positive intradermal tests ? some severe reaction
  to CM
• it is advisable to measure serum tryptase
  routinely in severe or 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

11
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 observed with its administration
• 2. gadolinium based CM--- intravascular, no above
  0.3 mmol kg1 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
  receptor?migrate into 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 XII
• 2. Decreased arachidonic acid from cell membranes
  
• ? production of PGs LTs (not sure)

12
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

13
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 hypotension)
• 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 (11000) ? IM of
  0.5 ml of 11000 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 (0.61.0 mg)
  are indicated 

14
Table 2. First-line emergency drugs and
instruments that should be in the room where
contrast medium is injected
15
Table 3. Simple guidelines for first-line
treatment of acute severe reactions to contrast
media
16
Thanks for your attention! ?
17
(No Transcript)
18
(No Transcript)
19
(No Transcript)
20
(No Transcript)