Anaphylactoid Reaction to Intravenous Contrast

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

A 46-year old Caucasian female (CF) was undergoing a CT scan of the abdomen for investigation of abdominal pain.

Past medical history (PMH)

Diabetes type 2 (DM2), obesity, hypertension (HTN), obstructive sleep apnea (OSA), asthma.


Glucotrol (glipizide), Norvasc (amlodipine), albuterol MDI PRN.

Physical examination


What happened?

A spiral CT imaging protocol was performed utilizing 100 ml of Ultravist 370 nonionic contrast intravenously. No oral contrast was administered.

After the intravenous contrast administration, the patient complained of difficulty breathing. The radiologist was called and upon initial evaluation the patient had evidence of bronchospasm that was confirmed on auscultation. She also stated that she had a history of asthma. Initially, two puffs of albuterol inhaler were administered. There was only minimal change in patient's symptoms.

Subsequently, one mL of intravenous epinephrine (1:10000) was administered. The patient's shortness of breath was relieved. However, she complained of tachycardia and severe cephalgia. Blood pressure was 180/100. Patient was monitored in the scanning room and then transferred to the recovery room where blood pressure diminished. She complained of persistent headache. At this time, the clinical service assumed care for the patient who was transferred to a regular medical floor.

What happened next?

Patient's abdominal pain persisted and she also complained of chest pain. After acute coronary syndrome was ruled out, a decision was made to repeat CT scan of the abdomen.

What premedication would you prescribe to prevent anaphylactoid reaction to IV contrast?

Prednisone 50 mg po x 1, 2 hours before test.
Prednisone 50 mg po x 1, 1 hour before test.
Benadryl 50 mg po x 1, 1 hour before test.

Benadryl (diphenhydramine) was used in the classic premedication protocols but steroids alone may be sufficient.

An older alternative protocol includes:

13 hours before the procedure: Prednisone 1 mg/kg PO
7 hours before the procedure: Prednisone 1 mg/kg PO
1 hour before the procedure: Prednisone 1 mg/kg PO
1 hour before the procedure: Diphenhydramine 1 mg/kg PO/IM
1 hour before the procedure: Cimetidine 4 mg/kg PO/IM (optional)

What happened?

A standard protocol CT abdomen and pelvis was done with oral contrast (Hypaque powder in 900 cc water) and 150 cc Ultravist 300, IV. The patient received a standard prep for reported contrast allergy prior to CT scan and no adverse reaction was reported.

She also had a chest CT with IV contrast (100 ml Isovue-370) without adverse reactions. Both CT scan were normal.

Final diagnosis

Anaphylactoid Reaction to Intravenous Contrast.


The incidence of reactions to radiocontrast media is between 4-8% of procedures. Anaphylaxis occurs in 1% and death in 0.001-0.009%. The reaction may be related to complement activation.

The cause of the anaphylactoid reaction is not the iodine in the IV contrast but his hypertonicity. Newer contrast media with low osmolarity are much safer and have only 1/3 to 1/4 of the tonicity of the older agents.

The rate of adverse events from radiocontrast media administration at 5-12% for high-osmolality contrast media and 1-4% for low-osmolality contrast media.

There are no diagnostic tests to predict an adverse reaction to IV contrast. Patients with a previous reaction have a 17-35% chance of recurrence on re-exposure .

Premedication with oral corticosteroids and antihistamines can be used to prevent adverse reactions to IV contrast media. The combination CS/AH decreases the risk of ADR to less than 1%. Benadryl was used in the classic premedication protocols but steroids alone may be sufficient.

Allergic reaction to IV contrast is usually anaphylactoid rather than anaphylactic reaction. Pretreatment protocols do not work for IgE-mediated anaphylaxis.

Anaphylactic reaction refers to a type I hypersensitivity reaction with mast cell/basophil degranulation mediated by antigen binding of specific IgE. Anaphylactoid reaction refers to a non–IgE-mediated mechanism of mast cell/basophil activation. Anaphylaxis refers to the physiologic events due to either mechanism.

Immediate-type adverse reactions to radiocontrast media are virtually always non-IgE mediated and have thus been previously termed “anaphylactoid reactions.” It was recently recommended that the term “nonimmunologic anaphylaxis” be used instead.

Figure 1. Mind map diagram of adverse reactions to drugs.

Does seafood allergy increase the risk of radiocontrast media reactions?

No. Patients with allergy to seafood and shellfish have specific IgE against proteins within the meat of the fish, and that iodine content plays no etiologic role. Radiocontrast media reactions are almost always non-IgE mediated and the the idea of cross-reactivity between iodine and radiocontrast media has been discounted.

Cross-reactivity to iodinated contrast media

Hypersensitivity to iodinated contrast media agents presents with cross-reactivity and is cell mediated. In a case report of 2 patients, skin prick test responses were negative, but patch test results were positive, suggesting participation of cellular mechanisms in these responses.

Evidence on allergy testing is best for iodinated RCM, limited for blue dyes, and insufficient for fluorescein

Classification of adverse reactions to drugs: "SOAP III" mnemonic (click to enlarge the image):

Adverse drug reactions (ADRs) affect 10–20% of hospitalized patients and 25% of outpatients.

Rule of 10s in ADR

10% of patients develop ADR
10% of these are due to allergy
10% of these lead to anaphylaxis
10% of these lead to death

Epinephrine (adrenaline) is the first-line the treatment of anaphylaxis. Adult intramuscular dose is 0.3 to 0.5 ml of 1:1,000 concentration. This should be given in the lateral aspect of the thigh by intramuscular injection. The dose can be repeated every 5 to 15 minutes, depending upon the response, for 3-4 doses. The same is true for children except the dose is 0.01 mg per kg (AAAAI Ask the Expert, 2012).

Dr Lockey: Radiocontrast Reactions: Rectifying Misconceptions About Shellfish Allergy and Iodine


50% of hypersensitivity reactions to contrast media may be caused by an immunological mechanism. Allergy, 2009.

Clinical review: ABC of allergies, Adverse reactions to drugs. Daniel Vervloet, Stephen Durham. BMJ 1998;316:1511-1514.
Contrast Medium Reactions, Recognition and Treatment. eMedicine, 2005.
Adverse Reactions to Contrast Material: Recognition, Prevention, and Treatment. American Family Physician, 2002.
Chapter 92 – Drug Allergy. N. Franklin Adkinson Jr. Adkinson: Middleton's Allergy: Principles and Practice, 6th ed. Online access from MDConsult.
Adverse Drug Reactions: Types and Treatment Options. AFP, 2003.
Advances in basic and clinical immunology in 2007. Journal of Allergy and Clinical Immunology - Volume 122, Issue 1 (July 2008).
Seafood Allergy and Radiocontrast Media: Are Physicians Propagating a Myth? Andrew D. Beaty, MD, Philip L. Lieberman, MD, Raymond G. Slavin, MD. American Journal of Medicine,Volume 121, Issue 2, Pages 158.e1-158.e4 (February 2008).
'Iodine allergy' label is misleading - Australian Prescriber
AAAAI explains why there is no IgE antibody-mediated "iodine allergy." IgE mediated seafood allergy has never been attributed to iodine, but rather to specific proteins in fish and shellfish
3% of patients who are exposed to iodinated contrast media develop delayed hypersensitivity reactions. Skin prick test is negative but the patch test is positive. Medscape and JACI, 2011.

Multiple choice questions

Chapter 57: Drug Allergy. Allergy and Immunology Review Corner: Chapter 57 of Pediatric Allergy: Principles & Practices, edited by Donald Y.M. Leung, et al.

Published: 08/24/2007
Updated: 06/22/2013


Anonymous said...

The article was informative. Thanks.

Anonymous said...

I had a reaction years ago. Getting a test next week with ivp dye and I am getting pre treatment hope it is ok