Download Radiocontrast Media

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
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Dana Wallace, MD
David Khan, MD
Paul Dowling, MD
Phil Lieberman, MD
David Lang, MD
Jay Portnoy, MD
Disclosures
(abbreviations below)
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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):
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TYPES AND CHARACTERISTICS OF
REACTIONS
RISK FACTORS FOR REACTIONS
DIAGNOSIS OF REACTIONS
TREATMENT OF REACTIONS
PREVENTION OF REACTIONS
Incidence of RCM Reactions
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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
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Immediate reactions
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Anaphylactoid
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Chemotoxic: systemic and local
Delayed reactions
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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
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Anaphylactoid (aka non-immunologic
anaphylaxis)
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Idiosyncratic
Does not require prior sensitization
Independent of infusion rate
Chemotoxic (cardio-, neuro-, or nephrotoxic)
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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
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It is not IgE mediated
Exact cause is unknown but possibly
due to:
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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
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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
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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
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Non-immediate cutaneous
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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:
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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!
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In 1975 Shehadi et. al noted the following
regarding patients with RCM reactions:
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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)
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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
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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
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2007 survey of 231 academic centers
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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
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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!
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Identify “false” risk factors such as
shellfish/iodine allergy in patient or other
family member as these may:
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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!
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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
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Flushing
Pruritus
Urticaria
Angioedema
Bronchospasm and wheezing
Laryngospasm/stridor
Hypotension
Shock/Loss of consciousness (rare)
Symptoms of Grade 1:
“Mild reactions” RCM Reactions
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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
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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
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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)
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Skin/mucosal symptoms
AND
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Airway compromise
OR
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↓ 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
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History of severe reaction
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Skin/mucosal symptoms
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Airway compromise
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↓ BP or Associated
symptoms
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GI symptoms with food
allergy
ANAPHYLAXIS or
ANAPHYLACTOID REACTION
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“SIMPLE DEFINITION”
An acute allergic-type reaction for which it is
known that there is potential for fatality
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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
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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
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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
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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
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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
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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
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Immediate Reactions
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Skin testing of no value
No blood tests are advised
Delayed Reactions
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Skin testing: prick, intradermal, patch
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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
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Resuscitation training results
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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
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Epinephrine
Position Supine
Oxygen
H1 and H2 Antihistamines
IV Fluids
Steroids (?)
Anaphylaxis Treatment
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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
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Establish that the patient does not respond
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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
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Start compressions
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Center of breastbone between nipples
1 ½-2 inches depth in adults
Adult: 30:2
Child:
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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
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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
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Sitting upright has been associated with
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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.
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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
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.9 NaCl (isotonic crystalloid)
Hydroxyethyl starch (Hespan) (colloid) if saline
not effective
IV FLUIDS
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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
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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)
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H2 ANTIHISTAMINES
 May reduce
hypotension
 Ranitidine IV or IM
 PO if very mild
BEST WHEN USED
IN COMBINATION
BRONCOHODILATORS FOR SEVERE
BRONCHOSPASM
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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
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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
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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
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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
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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)
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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
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β-blocker-related anaphylaxis may be
more likely to be refractory to
management
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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
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MAO Inhibitors and Tricyclic
anti-depressants
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May prevent degradation of epinephrine and
accentuate its effect
Could produce hypertensive crisis
Delayed RCM Reactions:
Treatment
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Most do not require treatment
No controlled studies
Corticosteroids and H1 antagonists
employed empirically for moderate
severe and severe reactions
Vasovagal reactions to RCM
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Attributed to fluid shifts caused by the
infusion of a hypertonic solution
Expect hypotension with bradycardia
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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
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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
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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
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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

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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

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
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
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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
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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
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Pumphrey, R.S., Fatal posture in anaphylactic shock. J Allergy Clin Immunol, 2003. 112(2): p.
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References
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
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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.
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Shehadi, W.H., Adverse reactions to intravascularly administered contrast media. A
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Shehadi, W.H., Contrast media adverse reactions: occurrence, recurrence, and distribution
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Sibbald, B., E. Rink, and M. D'Souza, Is the prevalence of atopy increasing? Br J Gen Pract,
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Simons, F.E., First-aid treatment of anaphylaxis to food: focus on epinephrine. J Allergy Clin
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References
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

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Syakalima, M., et al., Comparison of attenuation and liver-kidney contrast of liver
ultrasonographs with histology and biochemistry in dogs with experimentally induced steroid
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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
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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.