Edouard J. Trabulsi, MD, FACS
Leonard G. Gomella, MD, FACS
BASICS
DESCRIPTION
• Allergy reactions to IV contrast used for radiologic imaging are common, can range from mild to moderate, and occasionally life threatening.
• Often an immune system–based response to IV administration of contrast used for common urologic studies such as excretory urography and CT.
• Contrast allergy and reactions can be divided into 3 groups:
– Idiosyncratic anaphylactoid reactions
– Nonidiosyncratic reactions
– Delayed reactions
• Reactions to MRI contrast media are discussed in Section II “Nephrogenic Systemic Fibrosis/Fibrosing Dermatopathy (NSF/NFD).”
• “Contrast Induced Nephropathy” is discussed in Section II.
EPIDEMIOLOGY
Incidence
• Overall rate of ADR (adverse drug reaction) for ionic high-osmolar contrast media (HOCM) is 11–12% and 0.2–3% for nonionic low-osmolar contrast media (LOCM) (1)[B]
• It is estimated that up to 12% of patients may experience a contrast-related reaction.
Prevalence
N/A
RISK FACTORS
• History of asthma/bronchospasm (10 times), previous reaction (5 times), allergy or atopy (2–3 times) (2)[B]
• Other significant risks include: Cardiac disease, dehydration, sickle cell disease, polycythemia, multiple myeloma, pheochromocytoma, renal disease, anxiety, and the use of ionic vs. nonionic contrast material
• Possible risk factors: β-blockers, IL-2, aspirin, NSAIDs
• Concomitant shellfish allergy or iodine allergy, while a common misnomer, does not confer a higher risk of cross-reaction to radiocontrast media (RCM)
Genetics
N/A
PATHOPHYSIOLOGY
• Idiosyncratic anaphylactoid:
– Not dose dependent
– Most serious and potentially fatal type of reaction
– Occurs without warning, previous exposure not a prerequisite, not preventable
– Not considered anaphylactic due to lack of IgE antibody formation
– Usually begins with or immediately after injection of RCM (<30 min)
• Nonidiosyncratic:
– Dose dependent
– Related to osmolality, chemical composition, volume, and concentration of contrast medium used
– Idiosyncratic and nonidiosyncratic reactions may be classified as minor, moderate, or severe
– Minor: Urticaria, nausea and vomiting, sense of warmth, pruritus, diaphoresis
– Moderate: Faintness, severe vomiting, facial edema, laryngeal edema, mild bronchospasm
– Severe: Hypotensive shock, pulmonary edema, respiratory arrest, seizures, cardiovascular collapse
• Delayed:
– Occurs 1 hr to 7 days from injection of RCM
– Usually mild to moderate, transient, and self-limiting
– Commonly includes rash, urticaria, pruritus, and erythema
ASSOCIATED CONDITIONS
• Asthma
• Cardiac disease
• Dehydration
• History of allergy or atopy
• Previous adverse drug reaction
• Renal disease
• Sickle cell disease
• Renal insufficiency
GENERAL PREVENTION
• Use of alternative imaging in patients with history of previous ADR
• These measures may decrease likelihood of ADR but will not eliminate all risk (3)[B].
– Use of nonionic LOCM
– Antihistamines (diphenhydramine 50 mg 1 hr prior to study). An H2-blocker can be used in conjunction with H1, but never without H1-blockers
– Preprocedure hydration
• Patients with pre-existing renal impairment should stop metformin 24 hr prior to procedure and be well hydrated to avoid RCM-related biguanide lactic acidosis and contrast-induced nephropathy.
– In patients with normal renal function on metformin the following comorbidities should prompt discontinuation of metformin before the contrast:
Liver dysfunction, alcohol abuse, cardiac failure, myocardial or peripheral muscle ischemia, sepsis
• To limit risk for contrast-induced nephropathy, special arrangements should be made with the radiology department for any patient with a GFR <60 mL/min/1.73 m2.
• Prevention in patient with known allergy:
– Review radiology department procedures at site where testing scheduled.
– Give methylprednisolone (Medrol) 32 mg PO 12 and 2 hr prior to scheduled test and 50 mg diphenhydramine
– Patients with allergies to other substances (food, medicines), with history of asthma, who are allergic to iodinated contrast, who are receiving gadolinium (or those with allergy to gadolinium who are to receive IV contrast) DO NOT need steroid prep.
DIAGNOSIS
HISTORY (4)
• Previous ADR
• Cardiac or renal disease
• Metformin with chronic renal diisease
• Allergies
PHYSICAL EXAM
• Monitor vital signs (BP, heart rate, respirations)
– Hypotension and rarely shock
• Observe for:
– Urticaria, bronchospasm, wheezing, stridor shortness of breath, flushing, pruritus, angioedema
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• In acute setting, no labs are usually needed
• Blood gas may be useful
• The following may be obtained immediately after the reaction to help with the diagnosis: Elevated tryptase or histamine (released from activated mast cells).
Imaging
N/A
Diagnostic Procedures/Surgery
N/A
Pathologic Findings
N/A
DIFFERENTIAL DIAGNOSIS
Complex of symptoms immediately after contrast administration supports diagnosis
TREATMENT
GENERAL MEASURES
• Any facility that administers IV contrast should be equipped to treat common reactions noted below as well as initial steps in cardiac/respiratory arrest.
• The American College of Radiology classifies acute contrast reactions and treatment in adults as noted below. Treatment is similar in children with appropriate dose modifications.
– Hives
Mild (scattered/transient): Observe or PO diphenhydramine or PO fexofenadine
Moderate (numerous/bothersome): PO/IM/IV diphenhydramine or PO fexofenadine
Severe (widespread/progressive): Consider IM/IV diphenhydramine; consider IM/IV epinephrine
– Diffuse erythema: IV access, monitor vitals, pulse oximeter, O2 mask
If hypotensive NS or LR IV bolus 1 L
If no fluid response consider IM/IV epinephrine
– Bronchospasm: IV access, monitor vitals, pulse oximeter, O2 mask
Mild: β-agonist inhaler (eg, albuterol); consider rapid response team or ER admit
Moderate: Consider IM/IV epinephrine; consider rapid response team or ER admit
Severe: IM/IV epinephrine and rapid response team/911
– Laryngeal edema: IV access, monitor vitals, pulse oximeter, O2 mask, IM/IV epinephrine; consider rapid response team/911 based on response
– Hypotension (systolic BP <90 mm Hg): IV access, monitor vitals, pulse oximeter, O2 mask, elevate legs 60°; consider NS or LR IV bolus 1 L
With bradycardia (pulse <60 BPM [vasovagal] as above; give atropine; consider rapid response team/911
With tachycardia (pulse >100 BPM [anaphylactoid reaction]) IM/IV epinephrine; consider rapid response team based on response
– Hypertensive crisis (DBP >120 mm Hg; SBP >200 mm Hg; IV access, monitor vitals, pulse oximeter, O2 mask; IV labet alol or nitroglycerine SL and furosemide; rapid response team/911
– Unresponsive and pulseless: Check for responsiveness; rapid response team/911; initiate CPR; apply AED device; epinephrine IV (10 mL 1:10,000)
– Pulmonary edema: IV access, monitor vitals, pulse oximeter, O2 mask; elevate head of bed; IV furosemide, IV morphine; rapid response team/911
– Seizures: Protect patient; turn on side to avoid aspiration; suction airway as needed; IV access, monitor vitals, pulse oximeter, O2 mask; if unremitting rapid response team/911 lorazepam IV
– Hypoglycemia: IV access, O2 mask; oral 2 sugar packets or 4 oz fruit juice or D50W I amp IV with D5W or D5NS 100 mL/h adjunctively; if no IV glucagon 1 mg IM
– Anxiety/panic attack: Diagnosis of exclusion; monitor for evolving reactions if present; IV access, monitor vitals, pulse oximeter; reassure patient
– Reaction rebound prevention: IV steroids help short-term recurrence but not acute treatment benefit; consider IV hydrocortisone/methylprednisolone with severe allergic reaction prior to transport to ED
MEDICATION
First Line
• Based on guidelines noted above (5):
– Albuterol: 2 puffs (90 mcg/puff)
– Atropine 0.6–1 mg slow IV with NS flush up to 3 mg
– Benadryl
25–50 mg PO
25–50 mg IV slowly over 2 min
– Epinephrine
0.3 mg (0.3 mL 1:1,000 solution) IM
EpiPen or (equivalent) IM 0.3 mL 1:1,000 solution
1 mL 1:10,000 solution slow IV injection over 5 min repeated every 5–10 min as needed for severe reaction
– Furosemide 20–40 mg IV over 2 min
– Fexofenadine: 180 mg PO
– Glucagon: 1 mg IM
– Hydrocortisone 200 mg IV over 2 min
– Labet alol: 20 IV over 2 min; double dose every 10 min PRN
– Lorazepam 2–4 mg IV slow push; 4 mg max
– Methylprednisolone: 40 mg IV over 2 min
– Morphine: 1–3 mg IV, repeat every 5–10 min PRN
– Nitroglycerine: 0.4 mg tablet SL repeat every 5–10 min PRN
Second Line
N/A
SURGERY/OTHER PROCEDURES
N/A
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
For life-threatening reactions: ABCs of resuscitation, IV fluids, vasopressors for BP support if IV fluids not adequate
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Depends on severity of ADR
• Risk of death of 1 in 170,000 for both ionic HOCM and nonionic LOCM
COMPLICATIONS
• Renal failure occurs in up to 5%
• Generally supportive measures only with renal function returning to normal in a few weeks
• Contrast-induced nephropathy (CIN)
FOLLOW-UP
Patient Monitoring
• Appropriate supportive measures until recovery depending on severity of ADR
• For patients with renal insufficiency on metformin follow-up renal function monitoring recommended.
Patient Resources
N/A
REFERENCES
1. Cochran ST, Bomyea K. Trends in adverse events from iodinated contrast media. Acad Radiol. 2002;9(suppl 1):S65–S68.
2. Hagan JB. Anaphylactoid and adverse reactions to radiocontrast agents. Immunol Allergy Clin North Am. 2004;24:507–519.
3. Liccardi G, Lobefalo G, Di Florio E, et al. Strategies for the prevention of asthmatic, anaphylactic and anaphylactoid reactions during the administration of anesthetics and/or contrast media. J Investig Allergol Clin Immunol.2008;18(1):1–11.
4. Schabelman E, Witting M. The relationship of radiocontrast, iodine, and seafood allergies: A medical myth exposed. J Emerg Med. 2010;39(5):701–707.
5. ACR Manual on Contrast Media Version 9 2013 (www.acr.org). Accessed October 2013.
ADDITIONAL READING
• Brockow K, Christiansen C, Kanny G, et al. Management of hypersensitivity reactions to iodinated contrast media. Allergy. 2005;60:150–158.
• Schopp JG, Iyer RS, Wang CL, et al. Allergic reactions to iodinated contrast media: Premedication considerations for patients at risk. Emerg Radiol. 2013;20(4):299–306.
See Also (Topic, Algorithm, Media)
• Contrast-Induced Nephropathy (CIN)
• Nephrogenic Systemic Fibrosis/Fibrosing Dermatopathy (NSF/NFD)
• Reference Tables: Contrast Agents, Genitourinary
CODES
ICD9
• 708.0 Allergic urticaria
• 995.0 Other anaphylactic reaction
• 995.27 Other drug allergy
ICD10
• L50.0 Allergic urticaria
• T50.8X5A Adverse effect of diagnostic agents, initial encounter
• T88.6XXA Anaphylactic reaction due to adverse effect of correct drug or medicament properly administered, initial encounter
CLINICAL/SURGICAL PEARLS
A shellfish or iodine allergy does not correlate with contrast media allergy.