Systemic Anaphylactoid Reactions to Contrast Media During Cardiac Catheterization Procedures

1
Systemic Anaphylactoid Reactions to Contrast
Media During Cardiac Catheterization Procedures

• Diagnosis, Prevention, and Treatment
• Brandon E. Brown, M.D.
• Department of Internal Medicine

2
Clinical Scenario

• HPI 65 yo WM with known ASCAD, HTN, DM, and
  dyslipidemia presents with a compelling history
  of USA. He indicates that during his last
  catheterization, ten years ago, he experienced
  anaphylaxis and was given epinephrine.
• Pmedhx. as above. No history of asthma,
  allergies
• Meds Atenolol, Atorvastatin, Benazepril, ASA
• Allergies NKDA
• PE non-contributory
• ECG new anterolateral T wave inversions
• Labs normal initial CK, CK-MB, and troponin I

3
Definition of Terms

• Anaphylactoid events vs. Anaphylaxis
• Anaphylaxis an immediate systemic reaction
  caused by rapid, IgE-mediated immune release of
  potent mediators from tissue mast cells and
  peripheral blood basophils
• Anaphylactoid events immediate systemic
  reactions that mimic anaphylaxis but are not
  caused by IgE-mediated immune responses

4
Incidence

• Radiocontrast material (RCM)
• Estimated that 8 million people receive RCM
  annually in U.S.
• Overall frequency of adverse reactions is 5 to
  8
• Life-threatening reactions occur less than 0.1
  with older (hyperosmolar) agents
• Mortality estimated at one in every 75,000
  patients
• With advent of second generation agents
  (low-osmolar or iso-osmolar agents) incidence of
  adverse reactions 1/5 that of first generation
  agents
• Neuget AI. Ghatak AT. Miller RL. Anaphylaxis in
  the United States an investigation into its
  epidemiology. Archives of Internal Medicine.
  161(1)15-21, 2001 Jan 8.

5
What RCM do we use in our cardiac catheterization
lab?

• Optiray (Ioversol)
• A lower osmolar nonionic monomer
• Available in various osmolalities (ranging from
  355 to 792) and various levels of iodine content
  (160 to 350)

6
Clinical Presentation and Differential Diagnosis

• Anaphylactoid reactions clinically
  indistinguishable from anaphylaxis
• Suspected in any patient with hypotension during
  catheterization
• Diff. Dx. Includes cardiac and non-cardiac causes
• Vasovagal reaction bradycardia as opposed to
  typical tachycardia in anaphylactoid rxn
  (however, B-blockers and VVI PMs may blunt this
  response)
• CVP, SVR, and/or PCWP will be low reflecting
  hypoTN
• Usually occur within 20 min. of exposure

7
Pathophysiology

• The substantial reduction in toxicity with
  introduction of low-osmolar agents suggests
  hypertonicity of older agents played a role
• In vitro data indicates RCM can activate
  basophils and mast cells by an IgE-independent
  mechanism (ie anaphylactoid)
• RCMs have been shown to activate (directly and
  indirectly) complement, fibrinolytic, and kinin
  systems
• Several factors argue against an immunologic
  pathogenesis
• RCM reactions usually occur on first
  administration
• Relatively dose-independent (test dose not
  helpful)
• They do not always occur on subsequent exposure
  (estimated only 16)
• Efforts to raise anti-sera to RCM have confirmed
  its very weak immungenicity (related to chemical
  structure)

8
Pathophysiology (continued)

• However,
• Reports of detection of IgE antibodies specific
  for ioxaglate (Hexabrix) in patients repeatedly
  exposed to this RCM
• Mast cell activation demonstrated in vivo by
  detection of tryptase in serum of patients with
  RCM reactions
• Report of a patient who experienced a delayed
  hypersensitivity rxn. after second exposure to
  RCM who had previous positive patch testing
• Mita H, Tadokoro K, Akiyama K. Detection of IgE
  antibody to a radiocontrast medium. Allergy
  1998 531133-40.

9
Prevention

• Whos at risk?
• Those with previous RCM anaphylactoid reactions
• Atopic patients (2X risk)
• Patients on B-blockers
• Less common with intra-arterial vs. intravenous
  injection (but reaction more severe)
• No evidence to support that patients with known
  allergic sensitivity to iodine are at higher
  risk
• Coakley FV, Pannicck DM. Iodine allergyan
  oyster without a pearl? Am J Roengenol
  1997169951-2
• Leder R. How well does a history of seafood
  allergy predict the likelihood of an adverse
  reaction to IV contrast material? Am J Roentgenol
  1997906-7.

10
Prevention (continued)

• What can you do to minimize risk?
• Determine if study is essential
• Make certain patient understands risks
• Ensure proper hydration (consider early
  admission)
• Use non-ionic, lower osmolar RCM
• Use a pre-treatment medical regimen proven
• effective (next slide)

11
Prevention (continued)

• A Pre-treatment Medical regimen
• Steroids Prednisone 50mg p.o. 13, 7, and 1 hours
  before the procedure
• H1 Antihistamines Diphenhydramine 50 mg 1 hour
  before procedure
• Bronchodilators Ephedrine 25 mg or albuterol 4
  mg p.o. 1 hour prior to procedure
• H2 Antihistamines?
• Greenberger PA, Patterson R. The Prevention of
  Immediate Generalized Reactions to Radiocontrast
  Media in High-risk Patients. J Allergy Clin
  Immunol 199187867-872.
• Marshall GD Jr., Lieberman PL. Comparison of
  three pretreatment protocols to prevent
  anaphylactoid reactions to radiocontrast media.
  Annals of Allergy. 67(1)70-4, 1991 Jul.

12
Treatment

• Depends on severity of reaction and specific
  clinical manifestation
• Minor (erythema, pruritis),Moderate (urticaria,
  angioedema, bronchospasm), and Severe (shock,
  respiratory arrest) reactions
• Pharmacologic Agents
• Epinephrine for severe rxn. alpha effect
  causes vasoconstriction beta-1 effect causes
  chronotropy and inotropy beta-2 cause
  bronchodilation at cellular level, increases
  cAMP caution in B-blockers dose 0.3 cc of
  11000 dilution Q15 min. to max of 1 cc IV dose
  10ug/min bolus followed by gtt 1-4 ug/min.
• IV Steroids mechanism unclear-stabilizes cell
  membranes? Prevents biphasic rxn.?
  Hydrocortisone 400 mg IV
• Antihistamines inactivate unbound histamine
  Diphenhydramine 25-50 mg IV Cimetidine 300 mg
  IV or Ranitidine 50 mg IV
• IVF necessary for severe reactions NS vs. LR
• Glucagon 1-4 mg IV (or atropine)

13
Conclusions

• Relatively uncommon but potentially
  life-threatening
• Anaphylactoid reaction
• Pathogenesis in debate
• Importance of prevention
• Rapid diagnosis and treatment is essential

14
Additional References

• Practice parameters for the diagnosis and
  treatment of anaphylaxis, The Journal of Allergy
  and Immunology, volume 96, no. 5, part 2, Nov.
  1995.
• Allergy. Principles and Practice, fifth edition,
  Middlelton, jr., et al, vol. 2, pp.1079-1092.
• Optiray 350 package insert, September 2000
• Goss, et al., Systemic anapohylactoid reactions
  to iodinated contrast media during cardiac
  catheterization procedures guidelines for
  prevention, diagnosis, and treatment. Laboratory
  Performance Standards Committee of the Society
  for Cardiac Angiography and Interventions.
  Catheterization and Cardiovascular Diagnosis.
  34(2)99-104, 1995 Feb.
• Adkisson, Jr., Pathophysiology of contrast
  media anaphylactoid reactions new perspectives
  on an old problem. (letter, comment) Allergy.
  53(12)1111-1113, 1998 Dec.
• Bashmore et al., ACC/SCAI Clinical Expert
  Consensus Document On Catheterization Laboratory
  Standards. JACC Vol. 37, No. 8, June
  20012170-2714.