Cases & Commentaries

Reaction to Dye

Commentary By Richard Cohan, MD

The Case

A patient was referred to urology after having
several episodes of gross hematuria. The urologist thought that the
patient might have a renal mass and sent him to radiology for a CT
scan. The patient stated that he was not allergic to x-ray dye.
Therefore, the resident radiologist told the technologist to
proceed with contrast material administration for contrast
enhancement. Soon after the injection, the patient went into
anaphylactic shock on the CT table. Luckily, the patient was
rapidly resuscitated and suffered no permanent harm. On later
questioning, the patient stated that he was "very allergic" to
shellfish. On further inquiry, including an exhaustive review of
all of the patient's allergies, he stated that he was extremely
allergic to iodine in all forms.

The Commentary

Allergic-Like Reactions to Radiographic
Contrast Media

Although the near-universal replacement of
conventional high-osmolality ionic radiographic contrast agents
with low-osmolality nonionic agents (for intravascular use) has led
to a marked (four to five-fold) decrease in the incidence of
contrast reactions, such reactions will still be encountered by
nearly all radiologists. Approximately 3% of patients will
experience some type of reaction to these safer (but more
expensive) agents.(1) Fortunately,
the vast majority of adverse reactions are mild, self-limited, and
do not require any treatment. For example, severe reactions,
defined as reactions that require treatment, including dyspnea,
hypotension, loss of consciousness, or even cardiac arrest, are
encountered much less commonly. Such reactions were seen in only
0.04%, or one in 2500 patients, in one large study.(1) Fatal
contrast reactions are exceedingly rare. This is at least partially
due to the fact that if a severe reaction is aggressively and
appropriately treated, most patients will recover, and almost
always do so without any adverse long-term sequelae.

High-Risk Patients
It is essential to ask patients about any potential risk factors
prior to intravascular injection of iodinated radiographic contrast
material, so that high-risk patients can be prospectively
identified. The three most commonly encountered risk groups include
patients who have had a previous adverse reaction to an
intravascular iodinated contrast material injection, patients with
asthma, and patients who have any allergies.(1)
Older studies have also shown that patients with cardiac
arrhythmias (2), myasthenia
gravis of the central type (3),
pheochromocytomas (4), sickle cell
anemia (5), and
hyperthyroidism (6) are at risk
of having acute exacerbations of these diseases after ionic
contrast injection. Unfortunately, the risks of nonionic contrast
material injection in these patients are not well studied; however,
the risks, if there are any at all, are likely much
smaller.(5,7)

When interviewing patients prior to contrast
material injection, many health care providers, including
radiologists, technologists, nurses, and physicians, continue to
ask patients about seafood or "iodine" allergies. Specific concern
about iodine or seafood allergies is probably unjustified. The
iodine atom, present in every human being (since the thyroid gland
requires iodine to function), is too small to elicit an
antigen-antibody response; thus, patients cannot be allergic to
iodine by itself. Additionally, most adverse reactions to iodinated
contrast material do not represent true allergic reactions, as has
been demonstrated by the finding that anti-contrast material
antibodies are not consistently found in patients having adverse
allergic-like reactions.(8) The exact
mechanism of allergic-like contrast reactions is not known. Since
such reactions are not truly allergic, most researchers term these
as anaphylactoid rather than anaphylactic reactions.

The literature does not support the widespread
belief that patients with seafood allergies are particularly at
risk for an adverse reaction to iodinated contrast
material.(9) For example,
in one study, patients with shellfish/seafood allergies were no
more likely to react to an intravascular injection of ionic
contrast material than were patients with allergies to eggs, milk,
or chocolate.(10)
Accordingly, it is recommended that patients not be questioned
specifically about shellfish or iodine allergies
. Instead,
patients should be asked about any allergies. Patients with
multiple or severe allergies to any substances, as well as those
with histories of severe or poorly controlled asthma (particularly
if the asthma is currently active), should be treated with the same
caution.(9)

Pretreatment
Iodinated contrast material injection should be avoided, whenever
possible, in any patient who has had a previous moderate or severe
anaphylactoid reaction to iodinated contrast material. If contrast
material injection must be performed (because imaging with contrast
material is necessary and no alternative imaging study will provide
the desired information), corticosteroid premedication must be
provided, if at all feasible. It is also suggested that steroid
premedication be given to patients who have had previous mild
allergic-like contrast reactions, such as hives, although there is
no uniformity of opinion on this issue. Steroid premedication
should also be strongly considered in patients with multiple or
severe allergies to other agents, and in patients with symptomatic
or poorly controlled asthma. Two pretreatment regimens have been
widely researched. The first utilizes two oral 32 mg doses of
methylprednisolone administered 12 hours and 2 hours before
contrast material injection (11), while the
second requires administration of 50 mg of prednisone 13 hours, 7
hours, and 1 hour prior to contrast media injection.(12) The latter
regimen also usually includes a 1-hour pre-procedural oral dose of
50 mg of diphenhydramine.

There are two important issues concerning
premedication. First, premedication is known to be effective only
if the first dose of corticosteroids is administered at least 12
hours prior to intravascular contrast media injection.(11) While the
minimum duration of an effective steroid regimen has not been
determined, a single oral dose of steroids 2 hours prior to
injection is definitely of no benefit.(11)
Second, corticosteroid premedication reduces the number of adverse
reactions, but does not completely prevent them from occurring. For
example, in one study, total adverse reactions to ionic contrast
media in both high-risk and low-risk patients decreased from about
9% to 6% with a 12-hour steroid "prep."(11)
Adverse reactions requiring therapy decreased from 2.0%-2.2% to
1.2%. In another study, which included only high-risk patients,
premedication had a more pronounced effect, reducing the number of
reactions to ionic contrast material by two-thirds (from 9% to
3%).(12) In a more
recent study of both high-risk and low-risk patients, 6 to 24 hour
steroid regimens reduced the number of total reactions to nonionic
contrast material by a similar amount (from 4.9% to
1.7%).(13)

Treating Acute Contrast
Reactions

Treatment of acute allergic-like reactions to contrast material is
discussed in more detail elsewhere (14), but is
summarized in the Table.

Identifying and Communicating with
High-Risk Patients

It is exceedingly important that radiology departments have a
system in place to identify all patients at an increased risk of
developing an adverse reaction to radiographic contrast material.
At the least, the individual injecting the contrast material must
specifically ask patients whether they have had contrast material
before and, if so, how well they tolerated the injection. They must
also inquire about any "allergies" (including to contrast material)
and about the nature of such allergies. Since some patients will
not be able to distinguish a non-allergic reaction from an allergic
one, the interviewer must try to make such a distinction. Asking
patients who are to receive contrast material to fill out a brief
questionnaire adds another layer of safety.

If a patient does react to iodinated contrast
material, the radiologist must subsequently educate the patient
about the nature of the reaction and what future precautions are
necessary. The physician must also include a description of the
reaction in the official report. Finally, the patient should be
"flagged" as being at high-risk, so that if he or she returns to
the radiology department, the patient's risk can be easily
recognized. A contrast "alert" should be programmed into the
radiology information system, or the patient's name recorded on an
appropriate list in the radiology department. The more formalized
the process, the less likely that patient will receive a contrast
injection in the future without any advance awareness of the
increased risks of such an injection.

In the case presented here, it would have been
very helpful to know of the patient's being "very allergic" to
shellfish and to "iodine in all forms" prior to the administration
of contrast. However, as has been described, the term "iodine
allergy" is not accurate. This patient probably has multiple,
severe allergies. Upon obtaining such a history, the CT examination
should have been deferred and premedication with corticosteroids
instituted prior to imaging.

Take-Home Points

  • Every patient must be asked about prior
    contrast reactions, asthma, allergies, and other underlying
    diseases/medical problems. Specific questions with respect to
    seafood/shellfish or to iodine allergies are not necessary and can
    lead to confusion.
  • Contrast material injection should be
    avoided, if at all possible, in any patient who has had a previous
    moderate or severe allergic-like reaction to contrast material.
    Should re-injection be needed, steroid premedication should be
    provided for such patients, if at all possible.
  • Steroid premedication should be
    considered even in patients who have had previous mild
    allergic-like reactions.
  • Steroid premedication should also be
    considered in patients with multiple or severe true allergies to
    other substances or severe, poorly controlled, or currently
    symptomatic asthma.
  • Every radiologist must be aware of the
    appropriate ways to treat the various encountered acute contrast
    reactions.
  • After a reaction has occurred, the
    radiologist must educate the patient about the nature of the
    reaction and necessary future precautions. The reaction should be
    documented in the radiology report. Finally, the patient should be
    "flagged" as being at high-risk, so that if he or she returns to
    the radiology department, this risk can be recognized easily.

Richard
Cohan, MD
Professor, Department of Radiology
University of Michigan School of Medicine

References

1. Katayama H, Yamaguchi K, Kozuka T, Takashima
T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic
contrast media. A report from the Japanese Committee on the Safety
of Contrast Media. Radiology. 1990;175:621-8.[ go to PubMed ]

2. Lawton G, Phillips T, Davies R. Alterations in
heart rate and rhythm at urography with sodium diatrizoate. Acta
Radiol Diagn (Stockh). 1982;23:107-10.[ go to PubMed ]

3. Chagnac Y, Hadani M, Goldhammer Y. Myasthenic
crisis after intravenous administration of iodinated contrast
agent. Neurology. 1985;35:1219-20.[ go to PubMed ]

4. Raisanen J, Shapiro B, Glazer GM, Desai S,
Sisson JC. Plasma catecholamines in pheochromocytoma: effect of
urographic contrast media. AJR Am J Roentgenol. 1984;143:43-6.[ go to PubMed ]

5. Rao VM, Rao AK, Steiner RM, Burka ER, Grainger
RG, Ballas SK. The effect of ionic and nonionic contrast media on
the sickling phenomenon. Radiology. 1982;144:291-3.[ go to PubMed ]

6. Lorberboym M, Mechanick JI. Accelerated
thyrotoxicosis induced by iodinated contrast media in metastatic
differentiated thyroid carcinoma. J Nucl Med. 1996;37:1532-5.[ go to PubMed ]

7. Mukherjee JJ, Peppercorn PD, Reznek RH, et al.
Pheochromocytoma: effect of nonionic contrast medium in CT on
circulating catecholamine levels. Radiology. 1997;202:227-31.[ go to PubMed ]

8. Almen T. The etiology of contrast medium
reactions. Invest Radiol. 1994;29 Suppl 1:S37-45.[ go to PubMed ]

9. Coakley FV, Panicek DM. Iodine allergy: an
oyster without a pearl? AJR Am J Roentgenol. 1997;169:951-2.[ go to PubMed ]

10. Shehadi WH. Adverse reactions to
intravascularly administered contrast media. A comprehensive study
based on a prospective survey. Am J Roentgenol Radium Ther Nucl
Med. 1975;124:145-52.[ go to PubMed ]

11. Lasser EC, Berry CC, Talner LB, et al.
Pretreatment with corticosteroids to alleviate reactions to
intravenous contrast material. N Engl J Med. 1987;317:845-9.[ go to PubMed ]

12. Greenberger PA, Patterson R, Radin RC. Two
pretreatment regimens for high-risk patients receiving radiographic
contrast media. J Allergy Clin Immunol. 1984;74:540-3.[ go to PubMed ]

13. Lasser EC, Berry CC, Mishkin MM, Williamson
B, Zheutlin N, Silverman JM. Pretreatment with corticosteroids to
prevent adverse reactions to nonionic contrast media. AJR Am J
Roentgenol. 1994;162:523-6.[ go to PubMed ]

14. Cohan RH, Leder RA, Ellis JH. Treatment of
adverse reactions to radiographic contrast media in adults. Radiol
Clin North Am. 1996;34:1055-76.[ go to PubMed ]

Table

Table. Principles in Treating Acute Contrast
Reactions

Since anaphylactoid and anaphylactic
reactions have similar manifestations, treat them identically.

Patients with hives alone can either be
observed or treated with an antihistamine (such as diphenhydramine,
25-50 mg, PO, IM, or IV).

Patients with more severe reactions
should be closely observed, have vital signs checked frequently,
and receive high flow oxygen (ideally with oximetry
monitoring).

Patients with isolated bronchospasm can
be treated with a beta agonist inhaler (such as albuterol).

If there is no response to repeated
inhalers or if there is symptomatic laryngeal edema, consider
treatment with epinephrine (0.1-0.3 mg as initial dose, with total
dose titrated to symptoms). Slow intravenous injection (of 1-3 ml
of a 1:10,000 concentration) is preferred over subcutaneous
injection (as 0.1-0.3 ml of a 1:1,000 concentration). It is vital
to check and double-check the doses and concentrations, as
epinephrine overdoses can be fatal.

The unusual patient with pulmonary edema
(which may be cardiogenic or noncardiogenic) should sit up, receive
diuretics (beginning with 40 mg furosemide), and be moved to an
emergency department (or, for inpatients, a monitored unit), since
the reaction can be progressive and fatal.

The patient with hypotension should have
his or her legs elevated and receive rapid fluid resuscitation with
IV crystalloid solutions. If the patient is tachycardic and remains
hypotensive after fluid administration, pressors can be added. If
the patient is severely bradycardic and hypotensive, suspect a
vasovagal reaction. If needed, atropine can be used (dose of
0.5-1.0 mg) to increase the heart rate as well as cardiac
contractility.

Cardiorespiratory arrest should be
treated with basic and advanced cardiac life support, including
defibrillation if appropriate.