GENERAL COMMENTS FOR PRESENTERS

1
GENERAL COMMENTS FOR PRESENTERS

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

2
RADIOCONTRAST MEDIA ADVERSE REACTIONS

• American College of Asthma, Allergy, and
  Immunology
• Drug and Anaphylaxis Committee 2009

3
Authors Reviewers

• Dana Wallace, MD
• David Khan, MD
• Paul Dowling, MD
• Phil Lieberman, MD
• David Lang, MD
• Jay Portnoy, MD

4
Disclosures(abbreviations below)

• Dana Wallace, MD A, SA,M,SEP, SP, SCI
• David Khan, MD None
• Paul Dowling, MD None
• Phil Lieberman, MD A, D, E, G, IS, IN,N, P, SA,
  SP
• David Lang, MD GSK, G, N, AZ,SA,SP,M, MI
• Jay Portnoy, MD GSK, SCI, Ph

Alcon A, Astra-Zeneca AZ, DDey, EEndo,
GGenetech, GSK, IN Intelliject, IS Ista,
MEDA, MMerck, MI Medimmune, NNovartis,
PPfizer, PHPhadia, SA Sanofi-Aventis, SP
Schering/Plough, SCISciele, SEP Sepracor
5
Radiocontrast Media (RCM)

• TYPES AND CHARACTERISTICS OF REACTIONS
• RISK FACTORS FOR REACTIONS
• DIAGNOSIS OF REACTIONS
• TREATMENT OF REACTIONS
• PREVENTION OF REACTIONS

6
Incidence of RCM Reactions

• 11-12 for ionic, 5-12 high osmolar
• 3.13 for non-ionic contrast, 1-4 low osmolar
• Severe reactions 0.04 (lower osmolar) 0.22
  (ionic, high osmolar)
• Fatality 1-2100,000 exams (ionic non-ionic)
• 50-60 Million exams/year worldwide

Canter, L. Allergy Asthma Proc. 200526199-203.
Hagan. JB. Immuno Allergy Clin North Am 2004
24507-519. Katayama H. Radiology 1990, 175 (3)
621-268. Delaney A. BMC Medical Imaging 2006,
62. Kahn D et al. The Diagnosis and Management
of Anaphylaxis Practice Parameter 2008 update.
Annals, in press. Tramer. BMJ 2006333675.
7
Adverse Reactions to RCM

• Immediate reactions
• Anaphylactoid
• 94 lt20 minutes
• 40 fatalities respiratory decompensation
• Chemotoxic systemic and local
• Delayed reactions
• Hypersensitivity
• Other, e.g. Iodine mumps
• Vasovagal reaction

• Hagan. JB. Immuno Allergy Clin North Am 2004
  24507-519.

8
RCM ADVERSE REACTIONSIMMEDIATE IN ONSET
9
Anaphylactoid vs.. Chemotactic Reactions

• Anaphylactoid (aka non-immunologic anaphylaxis)
• Idiosyncratic
• Does not require prior sensitization
• Independent of infusion rate
• Chemotoxic (cardio-, neuro-, or nephrotoxic)
• Related to the chemical properties of the RCM
• Dose concentration dependent
• Occur more frequently in medically
  unstable/debilitated patients

Solensky R. Drug Allergy Practice Parameter.
Annals, in press.
10
Anaphylactoid RCM ReactionsMechanism 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.
199917469-496.
11
Risk Factors for Anaphylactoid Reactions

• Female gender (up to 20x)1
• History of previous reactions to radiocontrast
  media(5x)2
• Increased incidence 20-50 yrs. of age2
• Atopy (2-3x)2 and Asthma (10x)2 (not all articles
  agree as may just increase the severity of the
  reaction)4

• Lang, DM.JACI. 1995 95813-817. 2. Hagan. JB.
  Immuno Allergy Clin North Am
• 2004 24507-519. 3. Tramer MR. BMJ 2006 333
  675. 4. Brockow, K. Allergy, 2005.
• 60(2) p. 150-8.

12
Risk Factors for More Severe Anaphylactoid
Reactions

• Cardiovascular disease 1,2, 3
• Beta-blockers 1 (may also complicate Tx of
  reaction)2
• Debilitated, unstable, or elderly2

• Brockow, K. Allergy, 2005. 60(2) p. 150-8. 2.
  Hagan. JB. Immuno Allergy Clin North Am 2004
  24507-519. 3. Tramer MR. BMJ 2006 333 675.

13
Possible Risk Factors for RCM

• Non-immediate cutaneous
• Interleukin-2 Tx (Non-immediate cutaneous)1,2
• Serum Creatinine gt2.0 mg/dl2
• History of drug and contact allergy
• Aspirin/NSAIDS 1

1. Hagan. JB. Immuno Allergy Clin North Am 2004
24507-519.
2. Brockow, K. Allergy, 2005. 60(2) p. 150-8.
14
Risk Factors for Non-anaphylactoid Reactions

• Cardiovascular Dx
• Dehydration
• Hematologic conditions, e.g. sickle cell anemia
• Thrombotic tendencies
• Renal disease
• Anxiety and apprehension (?? No data)

Hagan. JB. Immuno Allergy Clin North Am 2004
24507-519.
15
Seafood Allergy is NOT a risk factor Possible
origin of the myth!

• In 1975 Shehadi et. al noted the following
  regarding patients with RCM reactions
• 15 of patients gave an unconfirmed history of
  shellfish allergy
• They surmised iodine in shellfish was responsible
  for the allergy. FALSE
• They surmised iodine in shellfish cross-reacted
  to iodine in RC. FALSE
• Note The allergens in shellfish is due to the
  protein components

Shehadi WH. Am J Roentgenol. 1975 124 145-152.
Beaty AD. American Journal of Medicine. 2008 121
(2) 158e.
16
Slight ? Risk of RCM Reactionfor an allergic
(atopic patient)

• Up to 46 population are atopic1
• Epidemiologic studies imply that atopic
  individuals are at risk of RCM reactions2
• Prospective analyses confirm ? risk3
• Atopics may have a more severe Reaction4
• Basophils in atopic individuals may be more
  sensitive to the degranulation effect of RCM
  agents

1) Shibbald, B. Br J Gen Pract. 1990 Aug
40(337)338-40. 2) Enright T et al. Ann Allergy
198962(4)302 5. 3) Lieberman P. et al. Clin
Rev in Aller and Immun. 1999 17(4) 469-496. 4)
Brockow,K. Allergy, 2005.
17
NOT JUST SHELLFISH!
46 population are atopic !
18
Facts on Shellfish Allergy and RCM Reactions

• Shellfish allergy is caused by the protein
  allergen (e.g. tropomyosin), not iodine
• Having shellfish /or RCM reactions are unrelated
  and coincidental (except for indicating atopy)
• Iodine and iodide are small molecules that do not
  cause anaphylactic or anaphylactoid reactions
• Povidone-iodine contact dermatitis (e.g. Betadine
  solution or mouthwash) does not increase risk of
  RCM reactions

Solensky R. The Diagnosis and Management of
Anaphylaxis Practice Parameter2009 update.
Annals, in press.
19
The Myth Lives On

• 2007 survey of 231 academic centers
• 61 inquire about seafood allergy before RCM
  administration
• 37 withhold RCM or recommend premedication when
  a patient has a history of seafood allergy
• 2005 survey of patients with seafood allergy
• 65 had been informed to avoid RCM
• 92 thought iodine caused their seafood allergy

Beaty AD. American Journal of Medicine. 2008 121
(2) 158e.
20
Help to Dispel the Myth!

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

21
Help to Dispel the Myth!

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

22
SYMPTOMS OF ANAPHYLACTOID REACTIONS
23
Common Symptoms of RCM Anaphylactoid Reactions

• Flushing
• Pruritus
• Urticaria
• Angioedema
• Bronchospasm and wheezing
• Laryngospasm/stridor
• Hypotension
• Shock/Loss of consciousness (rare)

24
Symptoms of Grade 1Mild reactions RCM
Reactions

• Limited nausea and vomiting
• Limited urticaria
• Pruritus
• diaphoresis

Hagan. JB. Immuno Allergy Clin North Am 2004
24507-519.
25
Symptoms of Grade 2moderate reactions to RCM

• Faintness
• Severe vomiting
• Profound urticaria
• Facial and laryngeal edema
• Mild bronchospasm

Hagan. JB. Immuno Allergy Clin North Am 2004
24507-519.
26
Symptoms of Grade 3Severe reactions to RCM

• Hypotensive shock
• Pulmonary edema
• Respiratory arrest
• Cardiac arrest
• Convulsions

Hagan. JB. Immuno Allergy Clin North Am 2004
24507-519.
27
Clinical Criteria for Anaphylaxis (any agent)
Anaphylaxis Anaphylactoid (non-immune
Anaphylaxis)
Anaphylaxis is likely if 1 or 3 set of criteria
are fulfilled
1

• Acute onset (min to hrs)
• Skin/mucosal symptoms
• AND
• Airway compromise
• OR
• ? BP or Associated symptoms

2

• 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

Hypotension within min. to hrs. after exposure to
known allergen
3
Sampson HA, et al. J Allergy Clin Immunol.
2005115584-591.
28
ANAPHYLAXIS orANAPHYLACTOID REACTION

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

29
RCM ADVERSE REACTIONSDELAYED
30
Delayed RCM Reactions

• Occur in 2 of patients1
• Occur between 1 hour and 1 week after RCM
  administration1
• Usually mild, cutaneous, self-limited1
• Serious reactions 0.004-0.0081
• No association with anaphylactoid reactions
• Controversial as reactions following CT with and
  without contrast may be equal.2

1. Lerch, M. Current Opinion in Allergy and
Clinical Immunology October 2004 - Volume 4 -
Issue 5 - pp 411-419 2. Yasuda, R.Invest Radiol,
1998. 33(1) p. 1-5. .
31
Delayed RCM Reactions Risk Factors

• Female
• Pt being treated with IL-2
• Frequency of previous reaction (possible) but
  recurrence is not consistent
• More frequent with non-ionic dimers
• Equal frequency with ionic non-ionic monomers

Current Opinion in Allergy and Clinical
Immunology October 2004 - Volume 4 - Issue 5 -
pp 411-419
32
Delayed RCM Reactions

• May be T-cell mediated
• The majority are maculopapular, pruritic rashes
  with fever
• Desquamation is frequent
• Predilection for palms
• Organ involvement. e.g. liver, kidneys, not
  uncommon
• Often patient has multiple drug sensitivities

Current Opinion in Allergy and Clinical
Immunology October 2004 - Volume 4 - Issue 5 -
pp 411-419
33
Delayed RCM ReactionsBiopsy findings

• Lymphocyte rich perivascular infiltrate
• Spongiosis
• CD4 memory cells
• Negative for eosinophils, complement, and
  antibodies
• Consistent with delayed hypersensitivity

Current Opinion in Allergy and Clinical
Immunology October 2004 - Volume 4 - Issue 5 -
pp 411-419
34
Delayed RCM Reactions Infrequent

• Cutaneous vasculitis
• Erythema multiforme
• Stevens Johnson syndrome
• Toxic Epidermal Necrolysis (TEN)
• Drug Rash with Eosinophilia and Systemic Symptoms
  (DRESS)

Current Opinion in Allergy and Clinical
Immunology October 2004 - Volume 4 - Issue 5 -
pp 411-419
35
DIAGNOSTIC STUDIES FORRCM ADVERSE REACTIONS
36
RCM Diagnostic Studies

• Immediate Reactions
• Skin testing of no value
• No blood tests are advised
• Delayed Reactions
• Skin testing prick, intradermal, patch
• Positive and negative
• No relationship between type of reaction or agent
  used
• Frequent cross-reactivity of agents
• Testing is not recommended

Kanny, G. J Allergy Immunol 2005 115 (1)
179-184.
37
TREATMENT OF RADIOCONTRAST MEDIA ADVERSE REACTIONS
38
The Treatment of Anaphylaxis and Anaphylactoid
Reactions is the same
39
Have a TX Plan Available
40
Enhancing Pediatric Safety during RCM Reaction

• Resuscitation training results
• Shortened the time to call code (98 vs. 140
  seconds)
• Shortened the time for requesting Epi (121 vs.
  163 sec) and O2 (40 vs. 89)
• Simulation training for radiology residents is
  valuable

Gaca AM. Radiology, 2007. 245 (1)236-244.
41
Broselow-Luten pediatric emergency tape Consider
using
Gaca AM. Radiology, 2007. 245 (1)236-244.
42
Sample Information sheet
Gaca AM. Radiology, 2007. 245 (1)236-244.
43
Anaphylaxis Treatment

• Epinephrine
• Position Supine
• Oxygen
• H1 and H2 Antihistamines
• IV Fluids
• Steroids (?)

44
Anaphylaxis Treatment

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

45
CPR

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

46
CPR

• Start compressions
• Center of breastbone between nipples
• 1 ½-2 inches depth in adults
• Adult 302
• Child
• 1-rescurer ratio is 302
• 2-rescurer ratio is 152

47
1 DRUG F0R ANAPHYLAXIS

• EPINEPHRINE
• (.01 mg/kg to max of .5 mg)
• IM in Lateral thigh (or SC upper arm)
• Repeat q 5 minutes PRN

48
IM vs. SQ Epinephrine
8 2 minutes

SHORTEST ONSET OF ACTION
-
34 14 (5 120) minutes p lt 0.05

-
Time to Cmax after injection (minutes)
Simons J Allergy Clin Immunol 113838, 2004
49
2 DRUG OXYGEN

• Any patient with Hypotension
• Any patient with 02 sat lt95
• Any patient requiring more than one Epi injection
• Face mask recommended over nasal prongs.
• Start with 6-8 Liter/minute

50
Position Patient Supine

• Sitting upright has been associated with
• Empty ventricle syndrome
• Pulseless Electrical Activity
• Increased Death
• 4/10 pre-hospital deaths associated with assuming
  upright or sitting position
• Pumphrey, R. J allergy Clin Immunol2003,
  112451-452.

51
Airway Support

• Bag-Valve-Mask Laryngeal Mask Airway

52
3 Drug IV FLUIDS
Bock SA, Munoz-Furlong A, Sampson HA. J Allergy
Clin Immunol. 2001107191193.

• For Hypotension (systolic lt100) 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

53
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

54
ANTIHISTAMINES (AFTER EPI)NEVER THE 1st Drug

• H2 ANTIHISTAMINES
• May reduce hypotension
• Ranitidine IV or IM
• PO if very mild

• 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)

BEST WHEN USED IN COMBINATION
55
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

56
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

57
EPINEPHRINE IV

• Always dilute to 110,000 or even 1100,000
  before administering
• Administer in step-wise increasing dose (see drug
  dose chart) finally moving to constant infusion
  of 30-100 ml/hour of 1100,000 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 12149, 2004.
58
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

59
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
60
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. Clinicians Manual on Anaphylaxis.
2005. Philadelphia, PA Current Medicine LLC
200533. 2 Lieberman P. Allergy Clin Immunol
IntJ World Allergy Org. 200416241-248. 3
Lieberman P. J Allergy Clin Immunol.
2005115S483-S523.
61
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

62
Beta Blockers ACE inhibitors/receptor blockers

• ß-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
63
MEDICATIONS FOR SPECIAL CONSIDERATION

• MAO Inhibitors and Tricyclic anti-depressants
• May prevent degradation of epinephrine and
  accentuate its effect
• Could produce hypertensive crisis

64
Delayed RCM ReactionsTreatment

• Most do not require treatment
• No controlled studies
• Corticosteroids and H1 antagonists employed
  empirically for moderate severe and severe
  reactions

65
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

66
PREVENTION OF RCM REACTIONS
67
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
333675.
68
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, 62. Tramer,
MR. BMJ 2006 333675.
69
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, 62. Tramer,
MR. BMJ 2006 333675.
70
Tramèr Systematic review of RCM
PremedicationSymptom category
Tramer, M. R et al. BMJ 2006333675
71
Tramèr Systemic ReviewSeverity Grade
Tramèr Systematic review of RCM
PremedicationSeverity Grade
Tramer, M. R et al. BMJ 2006333675
72
Benefit of using H1 Antihistamines in the
Prevention of RCM Reactions(Systematic
Review-Delaney)
Delaney A. BMC Medical Imaging 2006, 62.
73
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)3

• Greenberger, PA. Arch Intern Med 1985 1452197.
• Geenberger, PA. J Allergy Clin Immunol 1986
  77630.
• 3. Ring J. Int Arch Allergy Appl Immnol 1985
  78(1)9-14.

74
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, 62.
Tramer, MR. BMJ 2006 333675.
75
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
74540.
76
CURRENT RECOMMENDATIONSGIVEN A HISTORY OF
PRIOR ANAPHYLACTOID REACTION

77
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 175621. 2.
Greenberger PA. Arch Intern Med 1985 1452197.
3. Witten DM. Am J Roentgenol Radium Ther Nucl
Med 1973 119832. 4. Shehadi WH. Radiology 1982
14311. 5. Greenberger PA. J Allergy Clin Immunol
198474600. 6. Greenberger PA. J Allergy Clin
Immunol 1984 74540.
78
RCM Categories (examples)
safer groups
increased cost, but safer
79
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 cant
  be obtained
• Use a pre-medication regimen including systemic
  corticosteroids and H1 antihistamines

80
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 175621. 2.
Greenberger PA. Arch Intern Med 1985 1452197.
3. Witten DM. Am J Roentgenol Radium Ther Nucl
Med 1973 119832. 4. Shehadi WH. Radiology 1982
14311. 5. Greenberger PA. J Allergy Clin Immunol
198474600. 6. Greenberger PA. J Allergy Clin
Immunol 1984 74540. Kahn D et al. The Diagnosis
and Management of Anaphylaxis Practice Parameter
2008 update. Annals, in press.
81
Prevention of ReactionsEmergent 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

82
Delayed RCM ReactionsPrevention

• 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 2002225-466
83
Take Away PointsDO 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

84
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--scop
  e 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.

85
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.

86
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.

87
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.

88
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 contrast-enhanced
  media. Invest Radiol, 1998. 33(1) p. 1-5.

89
OPTIONAL SLIDES TO USE
90
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

• Brockow, K. Allergy, 2005. 60(2) p. 150-8. 2.
  Hagan. JB. Immuno Allergy Clin North Am 2004
  24507-519. 3. Tramer MR. BMJ 2006 333 675.