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GENERAL COMMENTS FOR PRESENTERS 1) 2) 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 RADIOCONTRAST MEDIA: ADVERSE REACTIONS American College of Asthma, Allergy, and Immunology Drug and Anaphylaxis Committee 2009 Authors & Reviewers Dana Wallace, MD David Khan, MD Paul Dowling, MD Phil Lieberman, MD David Lang, MD Jay Portnoy, MD 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 Radiocontrast Media (RCM): TYPES AND CHARACTERISTICS OF REACTIONS RISK FACTORS FOR REACTIONS DIAGNOSIS OF REACTIONS TREATMENT OF REACTIONS PREVENTION OF REACTIONS 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): 621268. 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. Adverse Reactions to RCM Immediate reactions Anaphylactoid Chemotoxic: systemic and local Delayed reactions 94% <20 minutes 40% fatalities= respiratory decompensation Hypersensitivity Other, e.g. Iodine mumps Vasovagal reaction 1. Hagan. JB. Immuno Allergy Clin North Am 2004; 24:507-519. RCM ADVERSE REACTIONS: IMMEDIATE IN ONSET 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. 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. 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 1. 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. Risk Factors for Anaphylactoid Reactions Cardiovascular disease 1,2, 3 Beta-blockers 1 (may also complicate Tx of reaction)2 Debilitated, unstable, or elderly2 1. 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. 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. Risk Factors for Nonanaphylactoid 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. 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. Slight Risk of RCM Reaction for 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. NOT JUST SHELLFISH! 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. 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. 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 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 SYMPTOMS OF ANAPHYLACTOID REACTIONS Common Symptoms of RCM Anaphylactoid Reactions Flushing Pruritus Urticaria Angioedema Bronchospasm and wheezing Laryngospasm/stridor Hypotension Shock/Loss of consciousness (rare) 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. 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. 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. Clinical Criteria for Anaphylaxis (any agent) Anaphylaxis = Anaphylactoid (non-immune Anaphylaxis) Anaphylaxis is likely if 1 or 3 set of criteria are fulfilled: 1 3 Acute onset (min to hrs) Skin/mucosal symptoms AND Airway compromise OR ↓ BP or Associated symptoms Hypotension within min. to hrs. after exposure to known allergen Sampson HA, et al. J Allergy Clin Immunol. 2005;115:584-591. 2 Exposure to known + 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 or ANAPHYLACTOID 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 RCM ADVERSE REACTIONS: DELAYED 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. . 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 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 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 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 DIAGNOSTIC STUDIES FOR RCM ADVERSE REACTIONS 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. TREATMENT OF RADIOCONTRAST MEDIA ADVERSE REACTIONS The Treatment of Anaphylaxis and Anaphylactoid Reactions is the same Have a TX Plan Available Treatment of Anaphylaxis in the Physicians Office Assess airway breathing, circulation, and orientation Inject epinephrine, 0.3 mg intramuscularly, in the vastus lateralis (lateral thigh) Activate emergency medical services depending upon severity or lack of response to treatment. Place patient in recumbent position and elevate the lower extremities, as tolerated Establish and maintain airway. Administer oxygen Establish an intravenous line for venous access and fluid replacement; keep open with normal Consider administration of nebulized albuterol, 2.5-5 mg in 3 mL of saline; repeat as necessary Consider administration of ancillary medications, such as H1, [H2] antihistamine, [and] or a systemic corticosteroid Modified from Cox, et. al. AAAAI/ACAAI JTF Report on omalizumab-associated anaphylaxis.J Allergy Clin Immunol. 2007 Dec;120(6):1373-7. 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. Broselow-Luten pediatric emergency tape: Consider using Gaca AM. Radiology, 2007. 245 (1):236-244. Sample Information sheet Gaca AM. Radiology, 2007. 245 (1):236-244. Anaphylaxis Treatment Epinephrine Position Supine Oxygen H1 and H2 Antihistamines IV Fluids Steroids (?) 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 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 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 # 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 IM vs. SQ Epinephrine 8 2+ minutes - 34 SHORTEST ONSET OF ACTION 14 (5 – 120) minutes + p < 0.05 Time to Cmax after injection (minutes) Simons: J Allergy Clin Immunol 113:838, 2004 # 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 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. Airway Support Bag-Valve-Mask Airway Laryngeal Mask #3 Drug IV FLUIDS Bock SA, Munoz-Furlong A, Sampson HA. J Allergy Clin Immunol. 2001;107:191–193. For Hypotension (systolic <100) which has not responded to first IM Epinephrine When there is shock in spite of increased vascular resistance 10% severe anaphylaxis not reversible with Epi* Select IV Fluids .9 NaCl (isotonic crystalloid) Hydroxyethyl starch (Hespan) (colloid) if saline not effective IV FLUIDS Administer rapidly 5-10 mg/kg crystalloid over first 5-10 minutes, and total of 20-30 mg/kg first hour Apply BP cuff to bag of fluid or withdraw fluid and use a stopcock to infuse with a large 50 cc syringe if IV pump is not available You may need to administer up to 50% of the intravascular volume ANTIHISTAMINES (AFTER EPI) NEVER THE 1st Drug H1 ANTIHISTAMINES Cannot abort anaphylaxis Onset of action slow relative to Epi Diphenhydramine (IV or PO) Cetirizine PO (may be used in lieu of diphenhydramine) H2 ANTIHISTAMINES May reduce hypotension Ranitidine IV or IM PO if very mild BEST WHEN USED IN COMBINATION BRONCOHODILATORS FOR SEVERE BRONCHOSPASM Nebulized albuterol or levalbuterol q 20 minutes as needed Nebulized Atrovent can be mixed with albuterol for 1-2 doses Glucagon may be especially useful for pt on beta blocker EPINEPHRINE IV Use only after 2-3 doses of IM and Volume Replacement No firmly established dose or regimen Reserve for non-responsive hypotension or cardiac arrest Risk of arrhythmias EPINEPHRINE IV Always dilute to 1:10,000 or even 1:100,000 before administering Administer in step-wise increasing dose (see drug dose chart) finally moving to constant infusion of 30-100 ml/hour of 1:100,000 dilution Connect to cardiac monitor as soon as possible Treat 30 minutes after symptoms resolve Dose escalates rapidly with cardiac arrest… up to10-50X starting dose Brown et al. EMMJ 12:149, 2004. VASOPRESSORS Use when IM Epi, fluid replacement, and IV epinephrine have failed Dopamine drip is preferred drug, titrate to maintain systolic BP (infusion dose on web site) Obtain central venous access as soon as possible Connect to cardiac monitor as soon as possible CORTICOSTEROIDS Limited data supporting usefulness in anaphylaxis Never a substitute for Epi Minimal benefit for initial treatment 4-6 hours before onset of action Questionable benefit for prolonged and biphasic reactions (higher dose [1-2mg/kg/day] + freq. dosing [q 6 hr for 38 hrs.])* 1 mg/kg of methylprednisolone IV For milder anaphylaxis consider .5 mg/kg of *2009 Draft Anaphylaxis PP prednisolone PO Patterns of Anaphylaxis Uniphasic1 Signs and symptoms occur then subside within 1 to 2 hours Biphasic2 Signs and symptoms resolve, but return between 1 and 48 hours later Protracted3 Signs and symptoms do not resolve with initial therapy and may last up to 32 hours despite aggressive treatment 1 Lieberman P. Clinician’s Manual on Anaphylaxis. 2005. Philadelphia, PA: Current Medicine LLC; 2005:33. Lieberman P. Allergy Clin Immunol Int—J World Allergy Org. 2004;16:241-248. 3 Lieberman P. J Allergy Clin Immunol. 2005;115:S483-S523. 2 60 Risk factors indicating a more prolonged observation period (8-24 hours) A reaction with hypotension requiring fluid administration An individual who has experienced a previous biphasic response A severe reaction with wheezing Beta Blockers & ACE inhibitors/receptor blockers β-blocker-related anaphylaxis may be more likely to be refractory to management Paradoxical bradycardia Profound hypotension Severe bronchospasm There is insufficient evidence to determine whether ACE inhibitors/receptor blockers increase either the risk of developing or difficulty of treating anaphylaxis Draft 2009 JTF Anaphylaxis PP MEDICATIONS FOR SPECIAL CONSIDERATION MAO Inhibitors and Tricyclic anti-depressants May prevent degradation of epinephrine and accentuate its effect Could produce hypertensive crisis Delayed RCM Reactions: Treatment Most do not require treatment No controlled studies Corticosteroids and H1 antagonists employed empirically for moderate severe and severe reactions Vasovagal reactions to RCM Attributed to fluid shifts caused by the infusion of a hypertonic solution Expect hypotension with bradycardia Caution: Bradycardia can also be present in anaphylactoid reactions Do not withhold epinephrine if in doubt Slow the infusion rate of RCM Treat with position reverse Trendelenburg, IV fluids, atropine PREVENTION OF RCM REACTIONS Prevention of 1st Reaction (when pt is at higher risk1) Use low osmolar contrast media (LOCM) agents for intravascular procedures Premedication not routinely used May be indicated in some cases based on the clinician's judgment2 Premedication for high osmolar contrast media (HOCM) agents for extravascular procedures not advised, lower risk 1. See slide 8-10. 2. Tramer, MR. BMJ 2006; 333:675. History of Prior Anaphylactoid Reactions Previous guidelines based on consensus Efficacy data on use of premedication with past anaphylactoid reaction is lacking Valid data on efficacy of drug combinations not available There is not 100% consensus of what constitutes optimal preventative therapy When using non-ionic contrast (almost universal) premedication may not be necessary Delany A. BMC Medical Imagima 2006, 6:2. Tramer, MR. BMJ 2006; 333:675. Evidence from 2 Systematic Reviews of RCM Pre-treatment No randomized trials exclusive to patients with history of anaphylactoid reaction to RCM Many trials excluded severe reactions to RCM Most studies used an unselected patient population Delany A. BMC Medical Imagima 2006, 6:2. Tramer, MR. BMJ 2006; 333:675. Tramèr Systematic review of RCM Premedication Symptom category Tramer, M. R et al. BMJ 2006;333:675 Tramèr Systematic review of RCM Premedication Severity Grade Tramèr Systemic Review: Severity Grade Tramer, M. R et al. BMJ 2006;333:675 Benefit of using H1 Antihistamines in the Prevention of RCM Reactions (Systematic Review-Delaney) Delaney A. BMC Medical Imaging 2006, 6:2. Benefit of using H1 + H2 Antihistamines in the Prevention of RCM Reactions Cimetidine added to regimens containing H1antihistamines and glucocorticoids did not further reduce the number of subsequent adverse reactions1,2 Cimetidine added to H1 antihistamine reduced overall side effects, excluding heat (6.1% vs.. 12.9% control) but effect on severe events unknown3 H1 (IV)+ H2 (IV) antihistamines angioedema (0.5% vs.. 4.1% control)3 1. Greenberger, PA. Arch Intern Med 1985; 145:2197. 2. Geenberger, PA. J Allergy Clin Immunol 1986; 77:630. 3. Ring J. Int Arch Allergy Appl Immnol 1985; 78(1):9-14. Benefit of using corticosteroids in the Prevention of RCM Reactions (Systematic Reviews) Use of two doses (e.g. methylprednisolone 32 mg) 6 hrs and 2 hrs prior to RCM administration May reduce risk of anaphylactoid reaction (systemic review did not produce pooled statistic)1 Reduced laryngeal edema (0.4% vs.. 1.4% control)2 Composite outcome (shock, bronchospasm, & laryngospasm) was reduced (0.2% vs.. 0.9% control)2 1. Delany A. BMC Medical Imagima 2006, 6:2. Tramer, MR. BMJ 2006; 333:675. Prevention of Reactions: Pre-medication - unclear benefit Ephedrine Has been used in premedication regimens However, multiple contraindications and weak evidence that it further reduces reactivity (beyond the two drug regimen) Not routinely recommended Geenberger, PA. J Allergy Clin Immunol 1984; 74:540. CURRENT RECOMMENDATIONS [GIVEN A HISTORY OF PRIOR ANAPHYLACTOID REACTION] Prevention of Reactions: If possible, avoid agent that caused reaction in past Use non-ionic, lower osmolar agents (LOCM) Some institutions use only LMW agents Consider these measures for patients who have prior history of reaction, since rate of recurrence is estimated at 17-60% 1. Katayama H. Radiology, 1990; 175:621. 2. Greenberger PA. Arch Intern Med 1985; 145:2197. 3. Witten DM. Am J Roentgenol Radium Ther Nucl Med 1973; 119:832. 4. Shehadi WH. Radiology 1982; 143:11. 5. Greenberger PA. J Allergy Clin Immunol 1984;74:600. 6. Greenberger PA. J Allergy Clin Immunol 1984; 74:540. RCM Categories (examples) *= safer groups $$ = increased cost, but safer Prevention of Reactions: Consider maintaining IV access throughout procedure Have personnel, medications, and equipment needed for treatment of allergic reactions always should be available when these agents are administered Obtain consent before administration Medic alert bracelets recommended for persons with history of prior reactions in case of emergent need for use of RMC when history can’t be obtained Use a pre-medication regimen including: systemic corticosteroids and H1 antihistamines Prevention of Reactions: Pre-medications Different regimens proposed over the years Best evidence is for use of Steroids and H-1 antihistamines used as follows: Prednisone: 50 mg orally given 13 hours, 7 hours, and 1 hour before in adults (in children, 0.5 to 0.7 mg/kg orally per dose, up to 50 mg) Diphenhydramine: 50 mg orally or parenterally given 1 hour before in adults (in children, 1.25 mg/kg orally, up to 50 mg) 1. Katayama H. Radiology, 1990; 175:621. 2. Greenberger PA. Arch Intern Med 1985; 145:2197. 3. Witten DM. Am J Roentgenol Radium Ther Nucl Med 1973; 119:832. 4. Shehadi WH. Radiology 1982; 143:11. 5. Greenberger PA. J Allergy Clin Immunol 1984;74:600. 6. Greenberger PA. J Allergy Clin Immunol 1984; 74:540. Kahn D et al. The Diagnosis and Management of Anaphylaxis Practice Parameter: 2008 update. Annals, in press. Prevention of Reactions: Emergent Procedures A rapid pretreatment protocol has been studied for patients with a previous immediate hypersensitivity reaction (IHR) to RCM requiring an emergency procedure. (14) Hydrocortisone: 200 mg IV immediately and every four hours until completion of procedure and Diphenhydramine: 50 mg PO/IV (or IM), one hour before RCM administration and The lowest osmolal RCM agent available should be used Delayed RCM Reactions: Prevention To prevent reoccurrence, IV bolus of corticosteroids immediately post-procedure has been suggested Romano case study for prevention of iobitridol-induced (angiograms) delayed hypersensitivity Cyclosporine 100 mg bid for one week prior and 2 weeks after procedure Methylprednisolone 40 mg daily one week prior and 2 weeks after procedure Romano, A. Radiology 2002;225-466 Take Away Points DO NOT FORGET Shellfish allergy is not a risk factor for RCM studies Iodine allergy is not a risk factor for RCM studies RCM reactions can be immediate or delayed in onset Epinephrine is the #1 drug for treatment of all anaphylaxis and anaphylactoid reactions Use non-ionic, low osmolar contrast agents Use a pre-treatment protocol for repeat RCM studies following a previous anaphylactoid RCM reaction Have a written anaphylaxis treatment plan and hold mock drills frequently References Beaty, A.D., P.L. Lieberman, and R.G. Slavin, Seafood allergy and radiocontrast media: are physicians propagating a myth? Am J Med, 2008. 121(2): p. 158 e1-4. Bock, S.A., A. Munoz-Furlong, and H.A. Sampson, Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol, 2001. 107(1): p. 191-3. Brockow, K., Contrast media hypersensitivity--scope of the problem. Toxicology, 2005. 209(2): p. 189-92. Brockow, K., et al., Management of hypersensitivity reactions to iodinated contrast media. Allergy, 2005. 60(2): p. 150-8. Brockow, K. and J. Ring, [Radiographic contrast media hypersensitivity. New understanding of pathophysiology with implications for patient management]. Hautarzt, 2005. 56(1): p. 32-7. Brown, D., A matter of the heart. Adv Nurse Pract, 2004. 12(7): p. 22-3. Canter, L.M., Anaphylactoid reactions to radiocontrast media. Allergy Asthma Proc, 2005. 26(3): p. 199-203. Cox, L., et al., American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol, 2007. 120(6): p. 1373-7. References Delaney, A., A. Carter, and M. Fisher, The prevention of anaphylactoid reactions to iodinated radiological contrast media: a systematic review. BMC Med Imaging, 2006. 6: p. 2. 10Enright, T., et al., The role of a documented allergic profile as a risk factor for radiographic contrast media reaction. Ann Allergy, 1989. 62(4): p. 302-5. 1Gaca, A.M., et al., Enhancing pediatric safety: using simulation to assess radiology resident preparedness for anaphylaxis from intravenous contrast media. Radiology, 2007. 245(1): p. 236-44. Greenberger, P.A., Contrast media reactions. J Allergy Clin Immunol, 1984. 74(4 Pt 2): p. 6005. Greenberger, P.A., et al., Emergency administration of radiocontrast media in high-risk patients. J Allergy Clin Immunol, 1986. 77(4): p. 630-4. Greenberger, P.A., R. Patterson, and R.C. Radin, Two pretreatment regimens for high-risk patients receiving radiographic contrast media. J Allergy Clin Immunol, 1984. 74(4 Pt 1): p. 540-3. Greenberger, P.A., R. Patterson, and C.M. Tapio, Prophylaxis against repeated radiocontrast media reactions in 857 cases. Adverse experience with cimetidine and safety of beta-adrenergic antagonists. Arch Intern Med, 1985. 145(12): p. 2197-200. References Hagan, J.B., Anaphylactoid and adverse reactions to radiocontrast agents. Immunol Allergy Clin North Am, 2004. 24(3): p. 507-19, vii-viii. Kanny, G., et al., T cell-mediated reactions to iodinated contrast media: evaluation by skin and lymphocyte activation tests. J Allergy Clin Immunol, 2005. 115(1): p. 179-85. Katayama, H., et al., Adverse reactions to ionic and nonionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology, 1990. 175(3): p. 621-8. Lang, D.M., et al., Gender risk for anaphylactoid reaction to radiographic contrast media. J Allergy Clin Immunol, 1995. 95(4): p. 813-7. Lerch, M. and W.J. Pichler, The immunological and clinical spectrum of delayed drug-induced exanthems. Curr Opin Allergy Clin Immunol, 2004. 4(5): p. 411-9. Lieberman, P.L. and R.L. Seigle, Reactions to radiocontrast material. Anaphylactoid events in radiology. Clin Rev Allergy Immunol, 1999. 17(4): p. 469-96. Munechika, H., R. Yasuda, and K. Michihiro, Delayed adverse reaction of monomeric contrast media: comparison of plain CT and enhanced CT. Acad Radiol, 1998. 5 Suppl 1: p. S157-8. Przybilla, B., et al., [Skin testing with the components of analgesics in patients with anaphylactoid hypersensitivity reactions to mild analgesics]. Hautarzt, 1985. 36(12): p. 682-7. Pumphrey, R.S., Fatal posture in anaphylactic shock. J Allergy Clin Immunol, 2003. 112(2): p. 451-2. References Ring, J., K.H. Rothenberger, and W. Clauss, Prevention of anaphylactoid reactions after radiographic contrast media infusion by combined histamine H1- and H2-receptor antagonists: results of a prospective controlled trial. Int Arch Allergy Appl Immunol, 1985. 78(1): p. 9-14. Romano, A., et al., Effective prophylactic protocol in delayed hypersensitivity to contrast media: report of a case involving lymphocyte transformation studies with different compounds. Radiology, 2002. 225(2): p. 466-70. Sampson, H.A., et al., Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol, 2005. 115(3): p. 584-91. Shehadi, W.H., Adverse reactions to intravascularly administered contrast media. A comprehensive study based on a prospective survey. Am J Roentgenol Radium Ther Nucl Med, 1975. 124(1): p. 145-52. Shehadi, W.H., Contrast media adverse reactions: occurrence, recurrence, and distribution patterns. Radiology, 1982. 143(1): p. 11-7. Sibbald, B., E. Rink, and M. D'Souza, Is the prevalence of atopy increasing? Br J Gen Pract, 1990. 40(337): p. 338-40. Simons, F.E., First-aid treatment of anaphylaxis to food: focus on epinephrine. J Allergy Clin Immunol, 2004. 113(5): p. 837-44. References Syakalima, M., et al., Comparison of attenuation and liver-kidney contrast of liver ultrasonographs with histology and biochemistry in dogs with experimentally induced steroid hepatopathy. Vet Q, 1998. 20(1): p. 18-22. Tramer, M.R., et al., Pharmacological prevention of serious anaphylactic reactions due to iodinated contrast media: systematic review. BMJ, 2006. 333(7570): p. 675. Witten, D.M., F.D. Hirsch, and G.W. Hartman, Acute reactions to urographic contrast medium: incidence, clinical characteristics and relationship to history of hypersensitivity states. Am J Roentgenol Radium Ther Nucl Med, 1973. 119(4): p. 832-40. Yasuda, R. and H. Munechika, Delayed adverse reactions to nonionic monomeric contrastenhanced media. Invest Radiol, 1998. 33(1): p. 1-5. OPTIONAL SLIDES TO USE Risk Factors for Anaphylactoid Reactions Cardiovascular disease 1,2, 3 Beta-blockers 1 (may also complicate Tx of reaction)2 Debilitated, unstable, or elderly2 Mastocytosis (potential)1 Viral infection at time (potential)1 Autoimmune Dz,.e.g. SLE (potential)1 1. 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.