Fast gadolinium-based contrast agent challenge test searching
for an alternative contrast media
To the Editor,
Gadolinium-based contrast agents (GBCA) are used in contrast-enhanced
magnetic resonance imaging. Hypersensitivity reactions (HSR) to GBCA are
scarce, with an incidence of 0.07% and a recurrence rate of 30%, being
urticaria the most common presentation (91%), with 0.52/10000 of severe
reactions reported1. Recommendation of an alternative
GBCA without checking tolerance is dangerous, due to high
cross-reactivity between them2. Moreover,
premedication is not enough1, showing an overall rate
of breakthrough reactions of 39%3.
Allergy studies to achieve a safe recommendation in HSR to GBCA have
been performed. Negative predictive value of skin-tests to GBCA has been
estimated in 84%1. Therefore, more than 10% of
patients could react using an alternative negative skin-tested GBCA, and
thus, good tolerance to GBCA should be confirmed through a drug
challenge-test (DCT)4. These tests are usually
performed at graded administrations, and with observation periods
between doses1,5. However, since GBCA is usually given
as a bolus during radiologic exams, DCT at slow rates cannot be
extrapolated to further administrations. Trying to avoid this
limitation, we study the tolerance of an alternative GBCA, by means of a
fast DCT, approaching the infusion rates used in clinical practice.
In accordance with the safety warnings to avoid linear GBCA, we have
only used the macrocyclic drugs gadobutrol (Gb) and gadoteric acid (Ga).
After obtaining signed informed consent from the patients, skin
pricktests (SPT) with undiluted macrocyclic GBCA commercial solutions
were done. When SPT at 20 min yielded negative results, intradermal
tests (IDT) with 1:10 dilutions were performed, with subsequent readings
at both 20 min and 24 hours.
A fast DCT with negative skin-tested GBCA was then performed, following
our methodology to study HSR to iodinated contrast media, previously
described elsewhere6. Doses were 0.2 mg/kg for Ga and
0.1 mg/kg for Gb. First, one third of the total dose of Ga was
administered at a rate of 120 cc/hour and, immediately after, the
remaining 2/3 at 80 cc/hour. In case of Gb, infusion rates were half
those of Ga, i.e., 1/3 at 60 cc/hour and 2/3 at 40 cc/hour. Total
infusion time was 8 minutes for both of them. Well-tolerated GBCA was
finally recommended for subsequent examinations, and its tolerance was
recorded if it was used later.
Study results of sixteen patients that were enrolled are summarized in
Table 1. They were 12 women and 4 men, with median age of 45.5 years
(range 28-73). Adverse reactions to GBCA were immediate in 13 patients
(12 urticaria or exanthema, and 1 anaphylaxis), and delayed exanthema in
the remaining 3. Gb was involved in 11 reactions, and unknown GBCA in
the other 5. Most of the patients (14/16) had been previously exposed to
GBCA.
Median delay to perform the allergy study was 10 months (range 2-72
months). All skin-tests were negative, except in one patient who showed
an immediate positive SPT to Gb, which had been the GBCA involved in the
adverse reaction. In our study, we have estimated a negative predictive
value of skintests to GBCA of 89%. DCT were negative in 14 patients (12
with Ga, and 2 with Gb). Finally, 15 out of 16 patients had an
alternative GBCA, avoiding the use of premedication. In fact, tolerance
has been confirmed in 7 of them in subsequent examinations.
Safety of our protocol has been confirmed because our 2 positive DCT
showed only mild reactions (delayed exanthema and immediate urticarial,
both with Ga), and also by including a patient with previous anaphylaxis
to GBCA.
Here we present a prospective protocol to identify a safe alternative
GBCA, including DCT at high infusion rates. Further studies will be
necessary on this item/to check this.