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GENERAL COMMENTS FOR PRESENTERS

Dive into the types, risks, diagnosis, treatment, and prevention of reactions to radiocontrast media. Learn about immediate and delayed responses, risk factors, and more.

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GENERAL COMMENTS FOR PRESENTERS

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  1. GENERAL COMMENTS FOR PRESENTERS • It is not intended for the presenter to use all of the slide deck as the audience will dictate the messages you want to convey • At times the slides on CPR may not be necessary or you may want to combine the info into a few key concepts, emphasizing Epinephrine use

  2. RADIOCONTRAST MEDIA: ADVERSE REACTIONS American College of Asthma, Allergy, and Immunology Drug and Anaphylaxis Committee 2009

  3. Authors & Reviewers • Dana Wallace, MD • David Khan, MD • Paul Dowling, MD • Phil Lieberman, MD • David Lang, MD • Jay Portnoy, MD

  4. Disclosures(abbreviations below) • Dana Wallace, MD: A, SA,M,SEP, SP, SCI • David Khan, MD: None • Paul Dowling, MD: None • Phil Lieberman, MD: A, D, E, G, IS, IN,N, P, SA, SP • David Lang, MD: GSK, G, N, AZ,SA,SP,M, MI • Jay Portnoy, MD: GSK, SCI, Ph Alcon= A, Astra-Zeneca= AZ, D=Dey, E=Endo, G=Genetech, GSK, IN= Intelliject, IS+ Ista, MEDA, M=Merck, MI= Medimmune, N=Novartis, P=Pfizer, PH=Phadia, SA= Sanofi-Aventis, SP= Schering/Plough, SCI=Sciele, SEP= Sepracor

  5. Radiocontrast Media (RCM): • TYPES AND CHARACTERISTICS OF REACTIONS • RISK FACTORS FOR REACTIONS • DIAGNOSIS OF REACTIONS • TREATMENT OF REACTIONS • PREVENTION OF REACTIONS

  6. Incidence of RCM Reactions • 11-12% for ionic, 5-12% high osmolar • 3.13% for non-ionic contrast, 1-4% low osmolar • Severe reactions 0.04% (lower osmolar) 0.22% (ionic, high osmolar) • Fatality 1-2:100,000 exams (ionic % non-ionic) • 50-60 Million exams/year worldwide Canter, L. Allergy Asthma Proc. 2005;26:199-203. Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519. Katayama H. Radiology 1990, 175 (3): 621-268. Delaney A.BMC Medical Imaging 2006, 6:2. Kahn D et al. The Diagnosis and Management of Anaphylaxis Practice Parameter: 2008 update. Annals, in press. Tramer. BMJ 2006;333:675.

  7. Adverse Reactions to RCM • Immediate reactions • Anaphylactoid • 94% <20 minutes • 40% fatalities= respiratory decompensation • Chemotoxic: systemic and local • Delayed reactions • Hypersensitivity • Other, e.g. Iodine mumps • Vasovagal reaction • Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519.

  8. RCM ADVERSE REACTIONS:IMMEDIATE IN ONSET

  9. Anaphylactoid vs.. Chemotactic Reactions • Anaphylactoid (aka non-immunologic anaphylaxis) • Idiosyncratic • Does not require prior sensitization • Independent of infusion rate • Chemotoxic (cardio-, neuro-, or nephrotoxic) • Related to the chemical properties of the RCM • Dose & concentration dependent • Occur more frequently in medically unstable/debilitated patients Solensky R. Drug Allergy Practice Parameter. Annals, in press.

  10. Anaphylactoid RCM Reactions:Mechanism of action • It is not IgE mediated • Exact cause is unknown but possibly due to: • Histamine release • Complement activation • Recruitment of various mediators • Direct mast cell degranulation Lieberman PL. Clin Rev Allergy Immunol. 1999;17:469-496.

  11. Risk Factors for Anaphylactoid Reactions • Female gender (up to 20x)1 • History of previous reactions to radiocontrast media(5x)2 • Increased incidence 20-50 yrs. of age2 • Atopy (2-3x)2 and Asthma (10x)2 (not all articles agree as may just increase the severity of the reaction)4 • Lang, DM.JACI. 1995; 95:813-817. 2. Hagan. JB. Immuno Allergy Clin North Am • 2004; 24:507-519. 3. Tramer MR. BMJ 2006; 333: 675. 4. Brockow, K. Allergy, 2005. • 60(2): p. 150-8.

  12. Risk Factors for More Severe Anaphylactoid Reactions • Cardiovascular disease 1,2, 3 • Beta-blockers 1 (may also complicate Tx of reaction)2 • Debilitated, unstable, or elderly2 • Brockow, K. Allergy, 2005. 60(2): p. 150-8. 2. Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519. 3. Tramer MR. BMJ 2006; 333: 675.

  13. Possible Risk Factors for RCM • Non-immediate cutaneous • Interleukin-2 Tx (Non-immediate cutaneous)1,2 • Serum Creatinine >2.0 mg/dl2 • History of drug and contact allergy • Aspirin/NSAIDS 1 1. Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519. 2. Brockow, K. Allergy, 2005. 60(2): p. 150-8.

  14. Risk Factors for Non-anaphylactoid Reactions: • Cardiovascular Dx • Dehydration • Hematologic conditions, e.g. sickle cell anemia • Thrombotic tendencies • Renal disease • Anxiety and apprehension (?? No data) Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519.

  15. Seafood Allergy is NOT a risk factor: Possible origin of the myth! • In 1975 Shehadi et. al noted the following regarding patients with RCM reactions: • 15% of patients gave an unconfirmed history of shellfish allergy • They surmised iodine in shellfish was responsible for the allergy. [FALSE] • They surmised iodine in shellfish cross-reacted to iodine in RC. [FALSE] [Note: The allergens in shellfish is due to the protein components] Shehadi WH. Am J Roentgenol. 1975; 124: 145-152. Beaty AD. American Journal of Medicine. 2008; 121 (2): 158e.

  16. Slight  Risk of RCM Reactionfor an allergic (atopic patient) • Up to 46% population are atopic1 • Epidemiologic studies imply that atopic individuals are at risk of RCM reactions2 • Prospective analyses confirm  risk3 • Atopics may have a more severe Reaction4 • Basophils in atopic individuals may be more sensitive to the degranulation effect of RCM agents 1) Shibbald, B. Br J Gen Pract. 1990 Aug; 40(337):338-40. 2) Enright T et al. Ann Allergy 1989;62(4):302– 5. 3) Lieberman P. et al. Clin Rev in Aller and Immun. 1999; 17(4): 469-496. 4) Brockow,K. Allergy, 2005.

  17. NOT JUST SHELLFISH! 46% population are atopic !

  18. Facts on Shellfish Allergy and RCM Reactions • Shellfish allergy is caused by the protein allergen (e.g. tropomyosin), not iodine • Having shellfish &/or RCM reactions are unrelated and coincidental (except for indicating atopy) • Iodine and iodide are small molecules that do not cause anaphylactic or anaphylactoid reactions • Povidone-iodine contact dermatitis (e.g. Betadine solution or mouthwash) does not increase risk of RCM reactions Solensky R. The Diagnosis and Management of Anaphylaxis Practice Parameter:2009 update. Annals, in press.

  19. The Myth Lives On • 2007 survey of 231 academic centers • 61% inquire about seafood allergy before RCM administration • 37% withhold RCM or recommend premedication when a patient has a history of seafood allergy • 2005 survey of patients with seafood allergy • 65% had been informed to avoid RCM • 92% thought iodine caused their seafood allergy Beaty AD. American Journal of Medicine. 2008; 121 (2): 158e.

  20. Help to Dispel the Myth! • Identify “false” risk factors such as shellfish/iodine allergy in patient or other family member as these may: • May delay or prevent a necessary procedure • May increase risk from side effects of unnecessary pre-medications • Instruct all staff to refrain from asking the patient if they have seafood or iodine allergy

  21. Help to Dispel the Myth! • Remove any reference to seafood allergy and iodine allergy from all consent forms and questionnaires • Hold inservice education session for all employees • Provide patient education about this myth, e.g. brochure or informative handout

  22. SYMPTOMS OF ANAPHYLACTOID REACTIONS

  23. Common Symptoms of RCM Anaphylactoid Reactions • Flushing • Pruritus • Urticaria • Angioedema • Bronchospasm and wheezing • Laryngospasm/stridor • Hypotension • Shock/Loss of consciousness (rare)

  24. Symptoms of Grade 1:“Mild reactions” RCM Reactions • Limited nausea and vomiting • Limited urticaria • Pruritus • diaphoresis Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519.

  25. Symptoms of Grade 2:“moderate reactions” to RCM • Faintness • Severe vomiting • Profound urticaria • Facial and laryngeal edema • Mild bronchospasm Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519.

  26. Symptoms of Grade 3:“Severe reactions” to RCM • Hypotensive shock • Pulmonary edema • Respiratory arrest • Cardiac arrest • Convulsions Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519.

  27. Clinical Criteria for Anaphylaxis (any agent) Anaphylaxis = Anaphylactoid (non-immune Anaphylaxis) Acute onset (min to hrs) Skin/mucosal symptoms AND Airway compromise OR ↓ BP or Associated symptoms Exposure to known allergen+ at least 2 items below within min to hrs History of severe reaction Skin/mucosal symptoms Airway compromise ↓ BP or Associated symptoms GI symptoms with food allergy Anaphylaxis is likely if 1 or 3 set of criteria are fulfilled: 1 2 Hypotension within min. to hrs. after exposure to known allergen 3 Sampson HA, et al. J Allergy Clin Immunol. 2005;115:584-591.

  28. ANAPHYLAXIS orANAPHYLACTOID REACTION • “SIMPLE DEFINITION” • An acute allergic-type reaction for which it is known that there is potential for fatality • Regardless of the severity of the presenting symptoms • For which immediate treatment has been shown to prevent progression of the disease process

  29. RCM ADVERSE REACTIONS:DELAYED

  30. Delayed RCM Reactions • Occur in 2% of patients1 • Occur between 1 hour and 1 week after RCM administration1 • Usually mild, cutaneous, self-limited1 • Serious reactions 0.004-0.008%1 • No association with anaphylactoid reactions • Controversial as reactions following CT with and without contrast may be equal.2 1. Lerch, M. Current Opinion in Allergy and Clinical Immunology: October 2004 - Volume 4 - Issue 5 - pp 411-419 2. Yasuda, R.Invest Radiol, 1998. 33(1): p. 1-5. .

  31. Delayed RCM Reactions: Risk Factors • Female • Pt being treated with IL-2 • Frequency of previous reaction (possible) but recurrence is not consistent • More frequent with non-ionic dimers • Equal frequency with ionic & non-ionic monomers Current Opinion in Allergy and Clinical Immunology: October 2004 - Volume 4 - Issue 5 - pp 411-419

  32. Delayed RCM Reactions • May be T-cell mediated • The majority are maculopapular, pruritic rashes with fever • Desquamation is frequent • Predilection for palms • Organ involvement. e.g. liver, kidneys, not uncommon • Often patient has multiple drug sensitivities Current Opinion in Allergy and Clinical Immunology: October 2004 - Volume 4 - Issue 5 - pp 411-419

  33. Delayed RCM Reactions:Biopsy findings • Lymphocyte rich perivascular infiltrate • Spongiosis • CD4+ memory cells • Negative for eosinophils, complement, and antibodies • Consistent with delayed hypersensitivity Current Opinion in Allergy and Clinical Immunology: October 2004 - Volume 4 - Issue 5 - pp 411-419

  34. Delayed RCM Reactions: Infrequent • Cutaneous vasculitis • Erythema multiforme • Stevens Johnson syndrome • Toxic Epidermal Necrolysis (TEN) • Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Current Opinion in Allergy and Clinical Immunology: October 2004 - Volume 4 - Issue 5 - pp 411-419

  35. DIAGNOSTIC STUDIES FORRCM ADVERSE REACTIONS

  36. RCM Diagnostic Studies • Immediate Reactions • Skin testing of no value • No blood tests are advised • Delayed Reactions • Skin testing: prick, intradermal, patch • Positive and negative • No relationship between type of reaction or agent used • Frequent cross-reactivity of agents • Testing is not recommended Kanny, G. J Allergy Immunol 2005; 115 (1): 179-184.

  37. TREATMENT OF RADIOCONTRAST MEDIA ADVERSE REACTIONS

  38. The Treatment of Anaphylaxis and Anaphylactoid Reactions is the same

  39. Have a TX Plan Available

  40. Enhancing Pediatric Safety during RCM Reaction • Resuscitation training results • Shortened the time to call code (98 vs. 140 seconds) • Shortened the time for requesting Epi (121 vs. 163 sec) and O2 (40 vs. 89) • Simulation training for radiology residents is valuable Gaca AM. Radiology, 2007. 245 (1):236-244.

  41. Broselow-Luten pediatric emergency tape: Consider using Gaca AM. Radiology, 2007. 245 (1):236-244.

  42. Sample Information sheet Gaca AM. Radiology, 2007. 245 (1):236-244.

  43. Anaphylaxis Treatment • Epinephrine • Position Supine • Oxygen • H1 and H2 Antihistamines • IV Fluids • Steroids (?)

  44. Anaphylaxis Treatment • Assess signs and symptom of Anaphylaxis • Review Airway, Breathing, Circulation, Defibrillator, and mental status • If severe anaphylaxis, staff to administer first dose of epinephrine using standing order

  45. CPR • Establish that the patient does not respond • Adult: Activate EMS immediately • Child: Give 5 cycles CPR then activate EMS • Head-tilt-chin lift • Look, listen, feel : 5-10 seconds • Give 2 breaths • Check carotid pulse and rate: 5-10 seconds

  46. CPR • Start compressions • Center of breastbone between nipples • 1 ½-2 inches depth in adults • Adult: 30:2 • Child: • 1-rescurer ratio is 30:2 • 2-rescurer ratio is 15:2

  47. # 1 DRUG F0R ANAPHYLAXIS EPINEPHRINE (.01 mg/kg to max of .5 mg) IM in Lateral thigh (or SC upper arm) Repeat q 5 minutes PRN

  48. IM vs. SQ Epinephrine 8 2minutes + SHORTEST ONSET OF ACTION - 34 14 (5 – 120)minutes p < 0.05 + - Time to Cmax after injection (minutes) Simons: J Allergy Clin Immunol 113:838, 2004

  49. # 2 DRUG OXYGEN • Any patient with Hypotension • Any patient with 02 sat <95% • Any patient requiring more than one Epi injection • Face mask recommended over nasal prongs. • Start with 6-8 Liter/minute

  50. Position Patient Supine • Sitting upright has been associated with • Empty ventricle syndrome • Pulseless Electrical Activity • Increased Death • 4/10 pre-hospital deaths associated with assuming upright or sitting position Pumphrey, R. J allergy Clin Immunol:2003, 112:451-452.

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