GENERAL COMMENTS FOR PRESENTERS

1) 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

2) 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, PhAlcon= 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 worldwideCanter, 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.

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 reaction1. 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 patientsSolensky 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 More Severe 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 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.

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 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.

NOT JUST SHELLFISH!46% population are atopic !

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

allergyBeaty AD. American Journal of Medicine. 2008; 121 (2): 158e.

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!

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)

Acute onset (min to hrs) Skin/mucosal symptomsAND Airway compromiseOR ↓ 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:

Hypotension within min. to hrs. after exposure to known allergen

1

3

2

Sampson HA, et al. J Allergy Clin Immunol. 2005;115:584-591.

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

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 monomersCurrent 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

sensitivitiesCurrent 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

hypersensitivityCurrent 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 FORRCM 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 recommendedKanny, 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 AvailableTreatment 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 fluidreplacement; 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 corticosteroidModified 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 sheetGaca 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 ANAPHYLAXISEPINEPHRINE

(.01 mg/kg to max of .5 mg)

IM in Lateral thigh (or SC upper arm)

Repeat q 5 minutes PRN

IM vs. SQ EpinephrineIM vs. SQ Epinephrine

Simons: J Allergy Clin Immunol 113:838, 2004

Time to Cmax after injection (minutes)Time to Cmax after injection (minutes)

8 2 minutes8 2 minutes++--

34 14 (5 – 120) minutes p < 0.05

34 14 (5 – 120) minutes p < 0.05

--++

SHORTEST ONSET OF ACTION

# 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 Laryngeal Mask Airway

#3 Drug IV FLUIDS

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

Bock SA, Munoz-Furlong A, Sampson HA. J Allergy Clin Immunol. 2001;107:191–193.

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 prednisolone PO*2009 Draft Anaphylaxis PP

Patterns of Anaphylaxis

60

1 Lieberman P. Clinician’s Manual on Anaphylaxis. 2005. Philadelphia, PA: Current Medicine LLC; 2005:33.2 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.

Signs and symptoms occur then subside within 1 to 2 hours

Uniphasic1

Uniphasic1

Biphasic2Biphasic2

Protracted3

Protracted3

Signs and symptoms resolve, but return between 1 and 48 hours later

Signs and symptoms do not resolve with initial therapy and may last up to 32 hours despite aggressive treatment

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 Systemic Review:Severity Grade

Tramer, M. R et al. BMJ 2006;333:675

Tramèr Systematic review of RCM Premedication

Severity Grade

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 H1-antihistamines 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)31. 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 PointsDO NOT FORGET

Shellfish allergy is not a risk factor for RCM studiesIodine allergy is not a risk factor for RCM studiesRCM reactions can be immediate or delayed in onsetEpinephrine is the #1 drug for treatment of all anaphylaxis and anaphylactoid reactionsUse non-ionic, low osmolar contrast agentsUse a pre-treatment protocol for repeat RCM studies following a previous anaphylactoid RCM reactionHave 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. 600-5.

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.

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OPTIONAL SLIDES TO USE

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

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.