This article discusses a study on allergic-type reactions to patients using high concentration contrast media versus patients receiving lower concentration contrast media.
Sergio Ginaldi, MD
Director of Ultrasound and CT, Tallahassee Memorial Hospital, FL
and Staff Radiologist, Section of Abdominal and Interventional
Radiology, Radiology Associates of Tallahassee, Tallahassee,
The advanced imaging capabilities of new, fast CT scanners have
prompted radiologists to consider adjusting contrast administration
protocols, specifically to use contrast media with a higher
concentration of iodine and to infuse it at a faster rate. To
evaluate the safety of such an approach, my colleagues and I
reviewed the incidence, type, severity and predictability of
adverse reactions to iodine contrast material in our radiology
practice. We also investigated the effectiveness in high-risk
patients of premedication for the prevention of allergic reactions
and prophylactic hydration for the prevention of
Our experience is that of a community practice in Tallahassee,
FL. The 20 radiologists in our group cover 2 major hospitals, where
we conduct approximately 26,000 CT scans a year. We also operate a
number of satellite locations, including Tallahassee Diagnostic
Imaging Center (TDI), where we perform 6,000 to 7,000 CT scans a
year. The data and experiences discussed in this article reflect
work done at the larger, regional hospital, Tallahassee Memorial
Hospital, and at TDI, the largest diagnostic center.
We retrospectively reviewed the medical records of all 30,301
patients who underwent pediatric and adult contrast-enhanced CT
examinations between August 1999 and October 2001. Of those, 78%
were imaged using Isovue 370 (Bracco Diagnostics, Princeton, NJ).
Another 8% were scanned using Ultravist (Berlex Laboratories,
Wayne, NJ) with an iodine concentration of 370 mg/mL, and 14% were
scanned using Ultravist with an iodine concentration of 300
The mean age of patients in the study was 58 years, and 63% were
female. The vast majority of patients, 21,459 (71%), were scanned
in the hospital. In both the hospital and the outpatient imaging
center, non-neurological studies were most common, outnumbering
neurological examinations by a ratio of almost 5-to-1 in the
hospital and >2-to-1 at TDI (Table 1). Non-neurological CT
studies include scans of the neck, chest, abdomen, pelvis, and
limbs in various combinations. As might be expected in a private
practice, the most common combination was a dual scan of the
abdomen and pelvis for abdominal pain. The next most common
referring diagnoses were appendicitis and diverticulitis. Studies
were tailored to the right lower quadrant in cases of suspected
appendicitis and consisted of a combined abdominal/pelvic scan in
cases of suspected diverticulitis. Chest CT for possible pulmonary
emboli was next in order of frequency.
We prepared patients for contrast-enhanced CT by first obtaining
a clinical history (Table 2). We focused on whether they had
previously experienced an adverse reaction to iodine or been
diagnosed with allergies, asthma, cardiac disease, renal disease,
multiple myeloma, or sickle cell anemia. We also determined whether
the patient had undergone more than one contrast-enhanced procedure
within the previous week, and measured baseline serum creatinine
levels as needed.
Any patient with a history of allergies to iodinated contrast
media or steroid-treated asthma underwent CT scanning at the
hospital, rather than the outpatient imaging center. Patients who
required premedication were also referred to the hospital for
scanning. Premedication consisted of antihistamines,
corticosteroids, and occasionally, a sedative administered just
before the contrast injection.
Patients whose serum creatinine levels were between 1.5 and 2.0
mg/dL, as well as those with multiple myeloma or recent sickle cell
crisis, underwent hydration therapy. This consisted of 100 mL of
0.45% normal saline infused at 100 mL/hr before contrast
administration and, if tolerated, 200 mL infused at the same rate
after the procedure.
We obtained peripheral venous access by inserting a 20-gauge
angiocatheter into the antecubital vein. Most patients were studied
in the supine position and, therefore, could be imaged using a
breathhold technique. The selection of scanning technique,
including slice width and pitch, depended on the size of the region
of clinical interest, the size and age of the patient, and the type
of CT scanner used. Two of our scanners were equipped with
single-detector helical technology and 2 with multidetector
The technique we use to administer contrast is shown in Table 3.
It varies with the iodine concentration of the contrast media, as
well as the type of scan. For the most common examination, a
combination of abdominal and pelvic scans, we use contrast media
with an iodine concentration of 370 mg/mL.
We use only nonionic contrast media and attempt to record all
adverse reactions that occur within 24 hours of contrast
administration. We observe patients for at least 48 hours for
evidence of worsening renal function, as gauged by an increase in
the serum creatinine level of 0.5 mg/dL or more above baseline. In
some cases we also check creatinine clearance and electrolyte
Nonfatal allergic-type reactions were equally common among
patients who received contrast media with an iodine concentration
of 370 mg/mL as among those who received contrast media with an
iodine concentration of 300 mg/mL (Table 4). In the outpatient
clinic, the rates of allergic-type reactions were 1.4% and 1.3%,
respectively, for a total of 120 patients. In the hospital, where
more than 21,000 patients were scanned using only
higher-concentration contrast media, the rate of allergic-type
reactions was even lower, <1%.
Only 0.3% of the patients scanned at the outpatient center
required medication for an allergic-type reaction, and of the 29
who did, only 3 were injected with epinephrine. There was no
appreciable difference in the rates of allergic-type reaction on
the basis of iodine concentration.
Of the more than 21,000 patients who were scanned in the
hospital, 95% had no clinical risk factors in their history to
prompt premedication. In this group, the incidence of allergic-type
reactions was very low, approximately 0.7%. In the 1,175 patients
who were premedicated, the incidence of allergic-type reactions was
substantially higher, approximately 4%. In other words, the chance
of an allergic-type reaction was more than 5.5 times as high in our
premedicated patients (those with risk factors) than in those
without risk factors for an allergic-type reaction (Table 5). The
most common allergic-type reactions were urticaria, itching,
sneezing, transient warmth, slight headache, flushing, and
Of the 191 patients who had allergic-type reactions in the
hospital, 48, or 25%, were premedicated. Only 0.6% of patients who
were scanned at the hospital required medication for an
allergic-type reaction. Of the 137 who did, only 9 were injected
Fatal Allergic Reactions
Of the 4,249 patients who were scanned using contrast media with
an iodine concentration of 300 mg/mL, 1 patient died. An additional
2 patients died of the more than 26,052 who were scanned with 1 of
2 contrast agents with an iodine concentration of 370 mg/mL. There
was no statistically significant difference between the two groups
in the incidence of death. None of the 3 patients was considered to
be at clinical risk or was premedicated.
We were able to collect data on renal function in a total of
8,543 patients. Of these, 8,122 were scanned in the hospital, and
421 were admitted from our outpatient facility. A total of 258
patients were identified as being at high risk for contrast
nephrotoxicity before scanning, and underwent hydration.
Nonetheless, we observed a high incidence of contrast
nephrotoxicity, in 87 (34%) of 258 high-risk patients (Figure 1).
Five patients required dialysis, 1 of whom continues on chronic
dialysis. This level of contrast-associated nephrotoxicity is lower
than is usually reported in the literature.
It may have been reduced by following strict pre-scan protocols,
including determination of baseline serum creatinine and the
prophylactic use of hydration.
We identified an additional 12 patients with nephrotoxicity in
the remaining group, none of whom were considered to be at high
risk and, therefore, did not receive hydration before contrast
administration. None required dialysis. Overall, about 1% of
patients monitored for renal function developed nephrotoxicity, and
only 0.06% of the monitored patient population required
There was little difference in the incidence of allergic-type
reactions among patients who received high-concentration contrast
agent (370 mgI/mL) and those who received a lower concentration
(300 mgI/mL); the rates for both were approximately 1%.
The majority of adverse reactions were mild. Reaction severity
also does not appear to depend on the concentration of iodine in
the contrast media.
Among patients with established risk factors, allergic-type
reactions were 4 times more frequent than among patients without
risk factors, despite premedication. Posttreatment medication for
allergic-type reactions, in our experience, was needed in <1% of
Contrast nephrotoxicity occurred in about 1% of patients without
predisposing risk factors. In patients known to be at high risk,
the incidence was >30%, despite hydration.
It is important to remember that, even if the incidence of
adverse reactions to nonionic contrast agents is very low,
reactions can happen at any time with any product. Physicians who
administer or authorize the use of intravenous contrast media need
to know how to monitor and treat adverse reactions. Patients at
risk for a reaction or nephrotoxicity should be well hydrated and
premedicated when possible. Guidelines for the diagnosis and
treatment of adverse reactions to radiocontrast media are available
from the American College of Radiology.