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345
Comparison of Iohexol with Barium in Gastrointestinal Studies of Infants and Children
Mervyn D. Cohen1 Richard Towbin2 Sarah Susan
This
children.
evaluates
iohexob
as a contrast
In the first part of the study,
was compared
Baker1 Davis1
in a double-blind
iohexol
manner
agent
in the
gastrointestinal
in concentrations
with barium.
tract
in
of 180 and 300 mg I/mb
Sixty-four
patients
were
studied.
No significant difference in changes of blood pressure and pulse rate was found between the three groups of patients studied. Diarrhea was significantly more common in the
C. Becker Daniel
study
children
E. Eggleston2 M. KehIer John A. Smith1 David A. Cory1 Susan J. White1
receiving
to previously
iohexol
identified
than in children
high-risk
factors
receiving
barium.
in the children,
The diarrhea
was not due
nor was it due to concurrent
medication. When image quality was assessed in each anatomic testinal tract, fewer nondiagnostic ratings occurred with barium barium, fewer ratings of poor mucosal coating and slightly fewer contrast density occurred. The second part of the study was iohexob 180 mg I/mI in 18 patients in whom barium was clinically
region of the gastrointhan with iohexol. With ratings of suboptimal an open evaluation of contraindicated. Three
of 53 assessments were nondiagnostic. Mucosab coating was poor in 6%, and contrast density was suboptimab in 8% of patients. The results of this study indicate that barium is the preferred contrast agent for routine evaluation of the gastrointestinal tract in children. Good-quality images can be obtained, however, with iohexol in concentrations of 180 or 300 mg I/mb, and iohexob is an excellent
Received September
June 1 1 , 1 990; accepted
after revision
12, 1990.
This work was supported in part by Sterling Drug Company. 1 Department of Radiology, Indiana University Medical Center, Riley Hospital for Children, 702 Bamhill Dr., Indianapolis, IN 46202-5200. Address reprint requests to M. D. Cohen. 2
Department
of Michigan, 48201.
of Radiology, 3901
Beaubien
Children’s Blvd.,
0361-803X/91/1562-0345 American Roentgen Ray Society
©
Hospital Detroit,
MI
contrast
in whom
barium
AJR
156:345-350,
agent
is relatively February
for evaluation or absolutely
of the gastrointestinal
tract
in those
patients
contraindicated.
1991
Three groups of contrast agents can be used to study the gastrointestinal tract [i ]. These are barium, high-osmolality water-soluble contrast agents, and lowosmolabity water-soluble contrast agents. Barium is a widely used, safe, and effective contrast agent, but both it and the high-osmobabity water-soluble contrast agents have disadvantages. For example, barium is undesirable in patients with suspected bowel perforation, and high-osmolality agents are undesirable in the preterm infant or patients with inflammatory bowel diseases. These disadvantages have been reviewed in detail elsewhere [i]. The low-osmolality contrast agents offer some advantages over barium and high-osmobality water-soluble contrast agents [1 ]. Of the bow-osmobality contrast agents, metnizamide has been studied most widely in the gastrointestinal tract [2iO]. Unfortunately, metnzamide is extremely expensive. For this reason, the efficacy of the newer, less expensive, low-osmolality water-soluble contrast agents in the gastrointestinal tract must be examined. Some reports of the use of iohexol, iopamidol, and ioxaglate describe the usefulness of these agents in the gastrointestinal tract [1 i -i 4]. Most of these reports are open studies without any blinded comparison. The objectives of the present study were twofold. In the first part, the safety of, tolerance of patients to, and quality of nadiobogic visualization with iohexol (i 80 and 300 mg I/mb) and barium were compared during and after examinations of the gastrointestinal tract in children. In the second part of the study, we evaluated the safety, tolerance, and efficacy of iohexol (i 80 mg b/mb) in patients in whom
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346
COHEN
barium is contnaindicated bowel perforation) who tion of the gastrointestinal
Subjects
(e.g., in a patient with possible were undergoing contrast examinatract.
at two centers.
designated
to monitor
At each center, a study
patients’
enrollment,
ization, contrast administration, adverse effects, Patients were considered eligible for inclusion showed signs or symptoms that necessitated examination
of
the
gastrointestinal
tract
and
random-
and data collection. in this study if they contrast-enhanced if they
were
younger
than i8 years old. Patients were included in the study if their parent or guardian gave informed written consent. The study had two parts: the iohexol/barium study and the iohexol-only study. Patients in whom the use of barium was not contraindicated were included in the iohexol/barium study. This was a comparative double-blind study. In some patients (e.g. , those with pneumoperitoneum or necrotizing enterocolitis) barium cannot be used. These patients were all studied with iohexol and formed the iohexol-only study. This was an open study. Patients were excluded if they were pregnant or lactating, if they
had had an enhanced examination
or were scheduled
for an enhanced
examination within 48 hr, if they had received another investigational drug, if they had previously been entered into the study, or if they
had conditions or suspected conditions that contraindicated the use of barium (iohexol/banium study only). The study was approved by the institutional review board of the two
participating
institutions.
Informed
consent
was
obtained
for
Patients
were
prepared
had nothing
according
to routine
hospital
procedure.
orally for at least 3 hr before the contrast
examination (older patients fasted for a longer period than younger patients did). All patients were permitted to receive routine prescribed medications (except for other investigational drugs), and all medications given within 24 hr before, during, and 24 hr after the examinations
were
recorded
factors to contrast included previous sion;
severe
asthma;
on
cardiac, was
the
case
report
forms.
All
coexisting
risk
administration were recorded. These risk factors reaction to contrast medium; diabetes; hyperten-
hay fever;
sensitivity
renal,
or
liver
drug allergy;
recorded
on
disease;
and food
the
data
sickle
allergy.
sheet
cell
disease;
Previous
but
did
not
images were acquired according to clinical need and routine departmental procedure. The total number of images acquired and therefore the radiation exposure was exactly the same as if the patient had not been in the study. Randomization of patient allocation for the iohexol/barium study was achieved with a computer-generated randomized code. All pawere
randomly
allocated
to receive either barium, iohexol 180
mg b/mI, or iohexol 300 mg I/mI. The investigator performing the examination and the patient were not told which contrast medium
was being used. Cups, straws, bags, and tubing were either opaque with tape. For single-contrast upper gastrointestinal ex-
or covered aminations,
the
For lower
barium
intestinal
concentration
was
single-contrast
barium
60%
weight
studies,
per
volume.
the concentration
was 30% weight per volume. Patients in whom barium was contraindicated received
were allocated to the iohexol 1 80 mg I/mI.
The volume radiologist
1991
to be administered
of blood pressure
to each
patient.
and pulse rate with the patient
supine
were obtained before, 1 hr after, and when possible at 6 and 24 hr after administration of contrast medium. Changes in vital signs from the baseline were evaluated. In addition, patients were observed for 1 hr after
the examination
for adverse
seen or their parents telephoned further
about
the occurrence
of adverse
Image quality was evaluated we made a radiologic patients were enrolled,
events.
All patients
were
24 hr after the examination
either
to inquire
events.
as follows: to facilitate patients’
care,
diagnosis at the end of each study. Once all two radiologists at each center reviewed and
graded the films obtained in both parts of the study in a blinded manner. An overall assessment of quality of radiologic visualization was recorded for each film series as well as individual assessments of the esophagus, stomach, duodenum, small bowel, and large bowel when seen. The quality of visualization was rated on a three-point scale (poor, good, and excellent). Poor visualization was considered nondiagnostic, whereas good and excellent visualizations were condiagnostic. For each segment
sidered
assessed within the gastrointestinal and mucosal coating were recorded of opacification was assessed on a three-point
sity of opacification density
tract, denas well. The scale of not
dense enough, optimal, and too dense. Mucosal coating sessed on a three-point scale of poor, good, and excellent. The iohexol-only study was an open study and therefore
was aswas not
to statistical analysis. For the iohexol/banium study, safety and efficacy were summarized by using standard deviations and ranges. Safety was assessed by comparison of the proportion of patients experiencing any adverse event and efficacy as the proportion of patients with diagnostic overall evaluations. Both were ana-
of contrast
performing
the
Each study was performed
iohexol-only
material study
and
in exactly
study.
These
given was determined was
based
lyzed by the standard contingency table method. Significant findings were followed with analyses considering each contrast medium pair. Additional testing was performed that examined differences in the quality
of visualization
sidered
either
poor,
possible
differences
among
contrast
good,
or excellent.
between
centers.
media,
with
visualization
All analyses
accounted
con-
for
contrast constitute
exclusion from the study. The patient’s age, sex, height, weight, race, and relevant medical history also were recorded. All of the
tients
February
subject
every patient. All patients
on weight,
Recordings
The study was performed was
AJA:156,
have been if the patient had not been entered in the study. The volume of contrast material given was therefore not influenced by the fact that the patient was in the study. Because of the large normal variation in the amount of contrast material given for any study, it was thought impossible to define a specific amount of contrast agent, based
and Methods
coordinator
ET AL.
on clinical
patients
by the need.
the same manner as it would
Results Eighty-two patients were ennobled, 64 in the iohexol/banium study and 1 8 in the iohexob-only study (Table 1). In the iohexob/banium study, patients from the three study groups are similar in terms of sex distribution, age, weight, and history of exposure to contrast medium. A few more patients with associated risk factors were in the barium group than in either of the other two groups (Table 1). Twenty-nine (69%) of 42 patients receiving iohexob and i 7 (77%) of 22 patients receiving barium from the iohexob/barium study and i 4 (78%) of i 8 patients in the iohexol-only study received
one
on more
concomitant
medications
within
24 hr
before and after the procedure. The most common medication classifications were antiasthma, anticonvulsant, antibiotic, and gastrointestinal. Risk factors were present in oven 60% of the patients (Table i); no difference in frequency was seen between the groups (p = .i 44). Allergy and age less than i year were the commonest risk factors.
AJR:156,
PEDIATRIC
February 1991
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TABLE
1: Demographic
Gb STUDIES:
Data, History
IOHEXOL
of Prior Contrast
VS
Exposure,
lohexol/Barium
BARIUM
347
and Risk Factors
lohexol-Only
Study
Demographic
Study
Parameter
lohexol
(1
80
lohexol (300
mg I/mI) No. of patients
21
Sex (M/F) Race
1 i/i
White
i9
Black
2
Age (years) Weight History
(kg) of exposure
4.7 i9.9
± ±
4.8 i9.3
Barium
mg I/mI)
mg I/mI)
2i
22
1 2/9
1 5/7
18 9/9
20
20
12
i
2
5.4 19.2
±
5.8
±
16.6
6
3.5
±
4.5
i .2
±
15.5
±
14.9
4.7
±
3.1 5.5
to con-
trast medium (V/N) Associated risk factor(s) including
0
lohexol (i 80
sensitivity
to ller-
gens or contrast (V/N)
medium
8/i 3
12/9
No significant difference in the volume of contrast material administered was found between the three groups in the iohexol/barium study (p = .63i). The volumes given were 5.2 ± 5.9 mb/kg (iohexol i 80 mg I/mb), 7.0 ± 7.0 (iohexol 300 mg I/mb), and 6.5 ± 3.3 mI/kg (barium). The difference in the dose per kilogram between the iohexol i 80 mg b/mb groups in the iohexob/barium study (5.2 ± 5.9 mb/kg) and in the iohexob-only study (9.2 ± 5.6 mI/kg) was statistically significant (p = .048). Comparing blood pressure and pulse nate recordings before and after contrast administration for patients in the iohexol/ barium study, we noted that nine patients had systolic blood pressure changes of 30 mm Hg or greater; these systolic blood pressure changes ranged from -38 to +63 mm Hg. Three patients had diastolic blood pressure changes of 30 mm Hg on greaten; these changes ranged from +30 to +38 mm Hg. Twenty-one patients had pulse rate changes of 30 beats pen minute or greater; these changes ranged from -64 to +98 beats per minute. Most of the changes represented increases from relatively low baseline recordings or decreases from relatively high baseline recordings. Most of the changes were transient and many were thought to be due to an agitated state of the patient before or when the vital sign measurements were taken. No difference in the changes of blood pressure and pulse rate was seen between the three groups of patients. No clinical adverse effects were ascribed to the vital sign changes, and no child required treatment on the basis of changes in vital signs. Adverse event information is summarized in Table 2. Eleven patients from the iohexol i 80 mg b/mb group had a total of i 7 adverse events, and nine patients from the iohexol 300 mg 1/ ml group had a total of 12 adverse events. One patient from the barium group had a single adverse event. The most common adverse event was mild to moderate diarrhea. Overall none of the adverse events were serious or life threatening and all were followed up until they resolved. Allocation of a patient to a high-risk subgroup did not predict an adverse event, as adverse events were detected more frequently in the bow-risk group than in the high-risk subgroup.
7/i 4
6/i 6
9/12
4/i 4
16/6
TABLE
2: Summary
i5/3
of Adverse
Iohexol(i80 mg
No. of patients Abdominal
pain
I/mI)
Events
in lohexob/Barium
Iohexol(300 mg
I/mI)
20
22
1
0 0 0 0 0 1 1
10
Fever Nausea
i i
Urticaria Vomiting
3
0 8 2 2 0 0
17
12
a
B a r tu m
20
Diarrhea
Totala
Study
i
Barium vs iohexol 180 is significant (p .005); barium vs iohexol 300 is (p = .003); iohexol 180 vs iohexol 300 is not significant (p = .75).
significant
The results of nadiobogic evaluation of the image quality for the various contrast agents are given in Tables 3-6. Tables 3, 4, and 5 give the analysis for nadiobogic visualization, mucosal coating, and contrast density for the three contrast agents used in the iohexol/banium study. The results are given separately for the duodenum, esophagus, stomach, small bowel, and large bowel. There are 64 separate evaluations for iohexob i 80 mg I/mI, 63 for iohexol 300 mg b/mb, and 78 barium assessments for individual organs. Of these, only six with iohexol 1 80 mg I/mb, seven with iohexol 300 mg b/mb, and three with barium were considered nondiagnostic (poor rating on radiographic visualization). With regard to mucosab coating, the ratings were good on excellent for 52 (80%) of iohexol 1 80 mg I/mb, 57 (90%) of iohexob 300 mg b/mI, and 77 (99%) of barium evaluations. Contrast density was considered optimal in 58 (9i %) of iohexol i 80 mg I/mI, 57 (90%) of iohexol 300 mg I/mb, and 73 (94%) Of barium evaluations. Table 6 gives similar data for iohexol 1 80 mg b/mI for the iohexol-onby study. Three of 53 iohexol 180 mg I/mI assessments were nondiagnostic (poor radiographic visualization). Mucosal coating was good or excellent in 50 cases (94%). Density was considered optimal in 49 evaluations (92%).
348
COHEN
TABLE
3: Radiologic
Efficacy
by Anatomic
Site for Barium
ET AL.
in Barium/lohexol
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Radio logic Visualization Site
Poor
M ucosal
lent
Diag-
2 0
6 3
13 17
21 20
90 100
Stomach
0
i 2
9
2i
Small Bowel Large Bowel
1 0
5 2
7 i
i3 3
Good
TABLE
+
Poor
Coating Percent
Ecel-
Good
Total
Diag-
nostica
Not Dense Enough
Optimal (%)
Dense
20 (95) 19 (95)
0 i (5)
Too
(%)
7 8
2i 20
95 100
(%) 1 (5) 0
16
5
2i
1 00
0
19 (90)
2 (10)
4 2
9 1
13 3
100 100
1 (7) 0
12 (93) 3 (i 00)
0 0
i 0
i3 12
i 00
0
92 i 00
0 0
1991
Density
nostica
Esophagus
Duodenum
a
Total
February
Study
Percent
Excel-
Good
AJA:156,
excellent.
4: Radiobogic
Efficacy
by Anatomic Radiologic
Site for lohexol
(i80
mg b/mb) in bohexol/Barium
Visualization
Mucosal
Study
Coating
Density
Not
Site Poor
Excel-
Good
Total
Percent
Diagnostica
Poor
Good
Excel-
lent
Total
Percent
Dense
Diagnostica
Enough
Optimal
(%)
(%)
a
Duodenum
2
13
1
i 6
88
5
i i
0
i6
69
2 (1 3)
i 4 (88)
Esophagus
i
14
4
19
95
2
i7
0
i9
89
2(u)
i7(89)
Stomach
0
14
4
i8
1 00
2
14
2
18
89
0
i 8 (i00)
Small Bowel Large Bowel
3 0
4 2
i i
8 3
63 1 00
3 0
4 3
i 0
8 3
63 i 00
Good
TABLE
+
2 (25) 0
6 (75) 3 (i 00)
excellent.
5: Radiobogic
Efficacy
by Anatomic Radiologic
Site for lohexob (300
mg I/mb) in bohexob/Barium
Visualization
Mucosal
Study
Coating
Site Poor
Good
Excel-
Total
Diagnostica Percent
Poor
Good
Excel-
Total
Density Not Dense Enough
Percent Diagnostica
Optimal
(%)
(%)
a
Duodenum
i
i 0
Esophagus
0
iO
Stomach Small Bowel Large Bowel
i 5 0
Good
TABLE
+
9 5 1
3 7
14 17
93 iOO
i 0
i 1 14
2 3
14 i7
93 100
i (7) 0
i 3 (93) i7(iOO)
5 2 4
15 12 5
93 60 i 00
0 4 i
11 6 0
4 2 4
i5 12 5
100 67 80
i (7) 4 (34) 0
i 4 (93) 8 (65) 5 (i 00)
excellent.
6: Radiologic
Efficacy
by Anatomic Radiologic
Site for lohexol
Good
in lohexol-Only
Visualization
Site
Poor
(180 mg I/mI)
Excel-
Total
Mucosal
Percent Diagnostica
Poor
Good
Excellent
Study Coating
Density
Total
Not Dense Enough
Percent Diagnostica
Optimal
(%)
(%)
S
Duodenum
i
8
4
i3
92
i
i i
i
13
92
i (8)
i 2 (92)
Esophagus Stomach Small Bowel
0 0 2
7 8
2 3 1
9 i4 1i
iOO iOO 82
0 0 2
8 14 9
i 0 0
9 i4 i1
iOO iOO 82
i (ii) 0 2 (1 8)
8(89) i4(iOO) 9 (82)
Large Bowel
0
3
3
6
1 00
0
5
i
6
100
0
Good
+
ii
6 (i 00)
excellent.
We evaluated the overall nadiobogic efficacy for each contrast agent. In the iohexol/banium study, barium was rated as excellent in i 2 cases and good in 10 cases; iohexol i 80 mg b/mb was rated as excellent in four cases, good in i 4 cases,
and poor in three cases; excellent in seven cases, cases. In the iohexol-only rated
as excellent
in six
iohexol 300 mg I/mI was rated as good in 1 2 cases, and poor in two study, iohexol i 80 mg b/mI was cases
and
good
in i 2 cases.
These
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AJR:156,
February
1991
PEDIATRIC
Gb STUDIES:
IOHEXOL
VS
349
BARIUM
data are for the radiologist’s impression of the overall quality of the entire study, but are not broken down by anatomic region. No statistical significant difference among the contrast media was found in the iohexol/barium study (p = .21 5) with regard to diagnostic (good + excellent) vs nondiagnostic (poor) assessments. However, when the individual classifications of overall quality (poor, good, excellent) are considered, a significant (p = .024) difference is seen among the contrast media owing to the greaten frequency of excellent assessments in the barium group relative to the iohexol i80 mg I/mI group. No significant difference was observed between the iohexol 180 and 300 mg b/mb groups when individual assessments of specific organs were compared in the iohexol/banium study (Table 2).
iohexol/barium study. For overall radiobogic efficacy, three of 2i studies with iohexob i80 mg b/mI in the iohexol/banium study were rated as poor, whereas no studies with this concentration were rated as poor for the iohexol-only study. Two reasons are believed to account for this difference. The patients receiving iohexol i80 mg I/mb in the iohexol-only study received a greater volume of contrast material pen kilogram of body weight (9.2 ± 5.6 ml) than did those patients in the iohexol/banium study (5.2 ± 5.9 mI/kg). Second, the age and weight of the patients in the iohexol-only study are very different from those of patients in the iohexol/banium study (Table i). This is because many of the clinical conditions for which barium is contraindicated exist in the newborn. In the small patients in the iohexol-only study, the lower body weight may result in less scattering of the X-ray beam with less boss of contrast on the radiograph. The concentration of
Discussion
iodine
In selected clinical situations, bow-osmolality water-soluble contrast agents have definite advantages over other contrast agents for examination of the gastrointestinal tract in children [i]. Early attempts to achieve low osmolabity involved dilution of high-osmolality contrast agents with resultant very low iodine concentrations [1 5]. For the past i 0 years, metnizamide has been used in almost isotonic solutions and with an iodine concentration of 1 80 mg I/mb to achieve good-quality images for the diagnosis of a variety of disorders in children, including bowel perforation [6-8] and necrotizing enterocolitis [4-i 0]. Unfortunately metnizamide is expensive. bohexob is similar to metrizamide, but less costly. Like metrizamide, it is extremely stable in bowel secretions [i 6] and has virtually no absorption from the normal bowel [1 6, 17]. Previous reports suggest that iohexol will have clinical usefulness similar to that of metrizamide in the intestinal tract, but unfortunately these reports do not include comparative double-blind evaluations of these agents [i 1 -i 3, i 8]. Evaluation of the radiobogic visualization, mucosal coating, and density of the contrast agent showed that barium was the preferred contrast agent for each of these evaluations, although the difference between barium and iohexol was not great. The particulate nature of the barium probably accounts for its preference for mucosab coating. The greaten attenuation of the X-ray beam by barium probably accounts for the fewer ratings of poor visualization with barium than with iohexol. The radiologists’ overall rating of radiobogic efficacy for each study showed that none of the barium studies was rated as poor, whereas five of the iohexol studies were assessed as poor. It should, however, be noted that 37 of the iohexol examinations in the iohexob/banium study were rated as good or excellent. Barium had more ratings of excellent than iohexob had. In summary, the results of the iohexob/banium study indicate that radiologic visualization with iohexol is good, but if the use of barium was not contraindicated, barium is the preferred agent. The iohexol-onby study evaluated iohexol i 80 mg b/mb in an open manner in patients for whom barium was contraindicated. A comparison of Table 4 (iohexob i 80 mg I/mb in the iohexol/barium study) and Table 6 (iohexob i 80 mg b/mb in the iohexol-only study) indicates fewer poor evaluations with this concentration of iohexob in the iohexol-only study than in the
degradation from scatter is greater in the larger patients. Both iohexol and barium were safe agents in that no major contrast reactions requiring therapeutic intervention on hospitalization were identified in either group. Table 2 shows, however, a much higher frequency of minor side effects with iohexol than with barium. In the iohexol/banium study, only one minor reaction occurred with barium, whereas 29 neactions occurred with iohexol. The frequency of these minor reactions did not correlate with the presence of high-risk factors in the patients’ histories. Of these adverse events, diarrhea was by far the commonest. The diarrhea was slightly more common in the patients with the bower concentration of iohexol. Ten patients receiving iohexol i 80 mg b/mI had diarrhea, compared with eight patients receiving iohexol 300 mg I/mI. The osmolality of the i 80 mg b/mb iohexol concentration is 408 mOsm/I and that of the 300 mg I/mb iohexol is 798 mOsm/I. Although the differences in the frequency of diarrhea are not statistically significant, they do raise the possibility that the toxic effect of iohexol causing diarrhea may not be purely an osmotic effect but might be due to some other irritating effect of this agent on the bowel. The osmolality of iohexob i 80 mg I/mb is only about 35% greaten than that of normal blood, and the high frequency of diarrhea is somewhat surprising if one postulates that the diarrhea is due purely to an osmotic effect of the contrast agent. Unfortunately a review of the literature does not provide additional answers. In three European studies with iohexob, a combined total of 1 12 patients had no episodes of diarrhea [19]. In another study that used iohexol 350 mg b/mI in adults, diarrhea was reported as a common event [20]. In i i fit adults, 150 ml of iohexol 350 mg b/mb caused diarrhea in 1 0 patients [2i ]. Finally, in a study of i 1 5 patients receiving either iohexol, iopamidol, or ioxaglate, no evidence of toxicity was reported. The difference in frequency of diarrhea in patients receiving iohexol as compared with the patients receiving barium is highly significant. Although many of our patients were receiving concomitant medication, the medications received did not differ among the three groups of patients, and we therefore believe that the diarrhea is a result of the iohexol and not of the concomitant medication. With regard to vital signs, the difference between the changes in blood pressure and pulse rate observed in the
is the
same
for each
group
of patients,
but
the
image
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350
COHEN
three groups was not statistically significant, and we believe that all of these changes can be accounted for by variations in the calmness or agitation of the patients when the readings were made. In summary, iohexob can be effectively used as a contrast agent in the gastrointestinal tract. The frequency of side effects is greaten than that with barium, but these side effects are mild. Although iohexob is not as good as barium for bowel visualization, it should provide an excellent substitute for the more expensive metrizamide for those patients in whom barium is relatively on absolutely contraindicated. The radiologists’ perception of image quality with iohexob is better in smaller than in larger patients. These data have been submitted to the Food and Drug Administration for approval to label iohexob “for oral use in the gastrointestinal tract in children.” Approval has not yet been obtained.
1 . Cohen MD. Choosing contrast media for the evaluation of the gastrointestinal tract of neonates and infants. Radiology 1987:162:447-456 2. Cohen M, Smith WL, Smith JA, Gresham EL, Schreiner A, Lemons J. The
use of metrizamide
(Amipaque)
to visualize the gastrointestinal
tract in
report. Clin Radiol 1980;31 :635-641 visualization of the gastrointestinal tract with metriz-
amide. Radiology 1982;i43:327-328 4. Cohen MD, Smith JA, Slabaugh RD, Rust RJ. Neonatal necrotizing enterocolitis shown by oral metrizamide (Amipaque). AJR 1982;138: ioi 9-i 023 5. Cohen MD, 5chreiner A, Grosfeld J, Weber T, Lemons J, Jansen R. A new look at the neonatal bowel: contrast studies with metrizamide (Amipaque). J Pediatr Surg 1983:18:442-448
AJR:i56,
6. Cohen MD, Weber TA, Grosfeld JL. Bowel perforation
February 1991
in the newbom:
diagnosis with metrizamide. Radiology 1984:150:65-69 7. Belt T, Cohen MD. Metrizamide evaluation of the esophagus AJR 1984;143:367-369
in infants.
8. Cohen MD, Jansen A, Lemons J, Schreiner A. Evaluation of the gasless abdomen in the newbom and young infant with metrizamide. AJR 1984:142:393-396
9. Johansen JG. Assessment of a non-ionic contrast medium the gastrointestinal tract. Invest Radiol 1978:13:523-527
(Amipaque)
in
1 0. Keller MS. Chawla HS. Neonatal metrizamide gastrointestinal series in suspected necrotizing enterocolitis. Am J Dis Child 1985;139:7i3-7i6 1 1 . Clarke EA, Dutton NE. Use of iohexol in the early determination of gastrointestinal perforation. J Pediatr Surg 1988;23: 1027-1 028 12. Brick SH, Caroline DE, Lev-Toaff AS, Friedman AC, Grumbach K, Radecki PD. Esophageal disruption: evaluation with iohexol esophagography. Radiology I988;169:141-143 13. Ratcliffe JF. The use of ioxaglate in the paediatric gastrointestinal tract: a report of 25 cases. Clin Radiol 1983;34:579-583 14. Ratcliffe JF. The use of low osmolality water soluble (LOWS) contrast media in the pediatric gastro-intestinal tract: a report of 1 i5 examinations. Pediatr Radiol 1986:16:47-52 15. Kuhns LA, Kanellitsas C. Use of isotonic water-soluble contrast agents for
gastrointestinal 16. Schwartzentruber
REFERENCES
children: a preliminary 3. Cohen MD. Prolonged
ET AL.
examinations
in infants. Radiology 1982;144:41 1 DJ, Billmire DF, Cohen M, Block T, Gunter M, Grosfeld JL. Use of iohexol in the radiographic diagnosis of ischemic bowel. J Pediatr Surg 1986:21:525-529 1 7. Mutzel W, Speck U. Pharmacokinetics and biotransformation of iohexol in the rat and dog. Acta Radiol Suppl 1980;362:87-92 18. Bell KE, McKinstry CS, Mills OM. lopamidol in the diagnosis of suspected upper gastro-intestinal perforation. Clin Radiol 1987;38: 165-1 68 19. Nycomed Clinical Report Nos. 120, 121 , and 130. Rensselaer, NY: Sterling Research Group, 1989 20. Sterling Research Group Clinical Study Report Nos. 137 and 632. Rensselaer, NY: Sterling Research Group, 1988 21 . Sterling Research Group Clinical Study Report No. 633. Rensselaer, NY: Sterling Research Group, 1988
345
Comparison of Iohexol with Barium in Gastrointestinal Studies of Infants and Children
Mervyn D. Cohen1 Richard Towbin2 Sarah Susan
This
children.
evaluates
iohexob
as a contrast
In the first part of the study,
was compared
Baker1 Davis1
in a double-blind
iohexol
manner
agent
in the
gastrointestinal
in concentrations
with barium.
tract
in
of 180 and 300 mg I/mb
Sixty-four
patients
were
studied.
No significant difference in changes of blood pressure and pulse rate was found between the three groups of patients studied. Diarrhea was significantly more common in the
C. Becker Daniel
study
children
E. Eggleston2 M. KehIer John A. Smith1 David A. Cory1 Susan J. White1
receiving
to previously
iohexol
identified
than in children
high-risk
factors
receiving
barium.
in the children,
The diarrhea
was not due
nor was it due to concurrent
medication. When image quality was assessed in each anatomic testinal tract, fewer nondiagnostic ratings occurred with barium barium, fewer ratings of poor mucosal coating and slightly fewer contrast density occurred. The second part of the study was iohexob 180 mg I/mI in 18 patients in whom barium was clinically
region of the gastrointhan with iohexol. With ratings of suboptimal an open evaluation of contraindicated. Three
of 53 assessments were nondiagnostic. Mucosab coating was poor in 6%, and contrast density was suboptimab in 8% of patients. The results of this study indicate that barium is the preferred contrast agent for routine evaluation of the gastrointestinal tract in children. Good-quality images can be obtained, however, with iohexol in concentrations of 180 or 300 mg I/mb, and iohexob is an excellent
Received September
June 1 1 , 1 990; accepted
after revision
12, 1990.
This work was supported in part by Sterling Drug Company. 1 Department of Radiology, Indiana University Medical Center, Riley Hospital for Children, 702 Bamhill Dr., Indianapolis, IN 46202-5200. Address reprint requests to M. D. Cohen. 2
Department
of Michigan, 48201.
of Radiology, 3901
Beaubien
Children’s Blvd.,
0361-803X/91/1562-0345 American Roentgen Ray Society
©
Hospital Detroit,
MI
contrast
in whom
barium
AJR
156:345-350,
agent
is relatively February
for evaluation or absolutely
of the gastrointestinal
tract
in those
patients
contraindicated.
1991
Three groups of contrast agents can be used to study the gastrointestinal tract [i ]. These are barium, high-osmolality water-soluble contrast agents, and lowosmolabity water-soluble contrast agents. Barium is a widely used, safe, and effective contrast agent, but both it and the high-osmobabity water-soluble contrast agents have disadvantages. For example, barium is undesirable in patients with suspected bowel perforation, and high-osmolality agents are undesirable in the preterm infant or patients with inflammatory bowel diseases. These disadvantages have been reviewed in detail elsewhere [i]. The low-osmolality contrast agents offer some advantages over barium and high-osmobality water-soluble contrast agents [1 ]. Of the bow-osmobality contrast agents, metnizamide has been studied most widely in the gastrointestinal tract [2iO]. Unfortunately, metnzamide is extremely expensive. For this reason, the efficacy of the newer, less expensive, low-osmolality water-soluble contrast agents in the gastrointestinal tract must be examined. Some reports of the use of iohexol, iopamidol, and ioxaglate describe the usefulness of these agents in the gastrointestinal tract [1 i -i 4]. Most of these reports are open studies without any blinded comparison. The objectives of the present study were twofold. In the first part, the safety of, tolerance of patients to, and quality of nadiobogic visualization with iohexol (i 80 and 300 mg I/mb) and barium were compared during and after examinations of the gastrointestinal tract in children. In the second part of the study, we evaluated the safety, tolerance, and efficacy of iohexol (i 80 mg b/mb) in patients in whom
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346
COHEN
barium is contnaindicated bowel perforation) who tion of the gastrointestinal
Subjects
(e.g., in a patient with possible were undergoing contrast examinatract.
at two centers.
designated
to monitor
At each center, a study
patients’
enrollment,
ization, contrast administration, adverse effects, Patients were considered eligible for inclusion showed signs or symptoms that necessitated examination
of
the
gastrointestinal
tract
and
random-
and data collection. in this study if they contrast-enhanced if they
were
younger
than i8 years old. Patients were included in the study if their parent or guardian gave informed written consent. The study had two parts: the iohexol/barium study and the iohexol-only study. Patients in whom the use of barium was not contraindicated were included in the iohexol/barium study. This was a comparative double-blind study. In some patients (e.g. , those with pneumoperitoneum or necrotizing enterocolitis) barium cannot be used. These patients were all studied with iohexol and formed the iohexol-only study. This was an open study. Patients were excluded if they were pregnant or lactating, if they
had had an enhanced examination
or were scheduled
for an enhanced
examination within 48 hr, if they had received another investigational drug, if they had previously been entered into the study, or if they
had conditions or suspected conditions that contraindicated the use of barium (iohexol/banium study only). The study was approved by the institutional review board of the two
participating
institutions.
Informed
consent
was
obtained
for
Patients
were
prepared
had nothing
according
to routine
hospital
procedure.
orally for at least 3 hr before the contrast
examination (older patients fasted for a longer period than younger patients did). All patients were permitted to receive routine prescribed medications (except for other investigational drugs), and all medications given within 24 hr before, during, and 24 hr after the examinations
were
recorded
factors to contrast included previous sion;
severe
asthma;
on
cardiac, was
the
case
report
forms.
All
coexisting
risk
administration were recorded. These risk factors reaction to contrast medium; diabetes; hyperten-
hay fever;
sensitivity
renal,
or
liver
drug allergy;
recorded
on
disease;
and food
the
data
sickle
allergy.
sheet
cell
disease;
Previous
but
did
not
images were acquired according to clinical need and routine departmental procedure. The total number of images acquired and therefore the radiation exposure was exactly the same as if the patient had not been in the study. Randomization of patient allocation for the iohexol/barium study was achieved with a computer-generated randomized code. All pawere
randomly
allocated
to receive either barium, iohexol 180
mg b/mI, or iohexol 300 mg I/mI. The investigator performing the examination and the patient were not told which contrast medium
was being used. Cups, straws, bags, and tubing were either opaque with tape. For single-contrast upper gastrointestinal ex-
or covered aminations,
the
For lower
barium
intestinal
concentration
was
single-contrast
barium
60%
weight
studies,
per
volume.
the concentration
was 30% weight per volume. Patients in whom barium was contraindicated received
were allocated to the iohexol 1 80 mg I/mI.
The volume radiologist
1991
to be administered
of blood pressure
to each
patient.
and pulse rate with the patient
supine
were obtained before, 1 hr after, and when possible at 6 and 24 hr after administration of contrast medium. Changes in vital signs from the baseline were evaluated. In addition, patients were observed for 1 hr after
the examination
for adverse
seen or their parents telephoned further
about
the occurrence
of adverse
Image quality was evaluated we made a radiologic patients were enrolled,
events.
All patients
were
24 hr after the examination
either
to inquire
events.
as follows: to facilitate patients’
care,
diagnosis at the end of each study. Once all two radiologists at each center reviewed and
graded the films obtained in both parts of the study in a blinded manner. An overall assessment of quality of radiologic visualization was recorded for each film series as well as individual assessments of the esophagus, stomach, duodenum, small bowel, and large bowel when seen. The quality of visualization was rated on a three-point scale (poor, good, and excellent). Poor visualization was considered nondiagnostic, whereas good and excellent visualizations were condiagnostic. For each segment
sidered
assessed within the gastrointestinal and mucosal coating were recorded of opacification was assessed on a three-point
sity of opacification density
tract, denas well. The scale of not
dense enough, optimal, and too dense. Mucosal coating sessed on a three-point scale of poor, good, and excellent. The iohexol-only study was an open study and therefore
was aswas not
to statistical analysis. For the iohexol/banium study, safety and efficacy were summarized by using standard deviations and ranges. Safety was assessed by comparison of the proportion of patients experiencing any adverse event and efficacy as the proportion of patients with diagnostic overall evaluations. Both were ana-
of contrast
performing
the
Each study was performed
iohexol-only
material study
and
in exactly
study.
These
given was determined was
based
lyzed by the standard contingency table method. Significant findings were followed with analyses considering each contrast medium pair. Additional testing was performed that examined differences in the quality
of visualization
sidered
either
poor,
possible
differences
among
contrast
good,
or excellent.
between
centers.
media,
with
visualization
All analyses
accounted
con-
for
contrast constitute
exclusion from the study. The patient’s age, sex, height, weight, race, and relevant medical history also were recorded. All of the
tients
February
subject
every patient. All patients
on weight,
Recordings
The study was performed was
AJA:156,
have been if the patient had not been entered in the study. The volume of contrast material given was therefore not influenced by the fact that the patient was in the study. Because of the large normal variation in the amount of contrast material given for any study, it was thought impossible to define a specific amount of contrast agent, based
and Methods
coordinator
ET AL.
on clinical
patients
by the need.
the same manner as it would
Results Eighty-two patients were ennobled, 64 in the iohexol/banium study and 1 8 in the iohexob-only study (Table 1). In the iohexob/banium study, patients from the three study groups are similar in terms of sex distribution, age, weight, and history of exposure to contrast medium. A few more patients with associated risk factors were in the barium group than in either of the other two groups (Table 1). Twenty-nine (69%) of 42 patients receiving iohexob and i 7 (77%) of 22 patients receiving barium from the iohexob/barium study and i 4 (78%) of i 8 patients in the iohexol-only study received
one
on more
concomitant
medications
within
24 hr
before and after the procedure. The most common medication classifications were antiasthma, anticonvulsant, antibiotic, and gastrointestinal. Risk factors were present in oven 60% of the patients (Table i); no difference in frequency was seen between the groups (p = .i 44). Allergy and age less than i year were the commonest risk factors.
AJR:156,
PEDIATRIC
February 1991
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TABLE
1: Demographic
Gb STUDIES:
Data, History
IOHEXOL
of Prior Contrast
VS
Exposure,
lohexol/Barium
BARIUM
347
and Risk Factors
lohexol-Only
Study
Demographic
Study
Parameter
lohexol
(1
80
lohexol (300
mg I/mI) No. of patients
21
Sex (M/F) Race
1 i/i
White
i9
Black
2
Age (years) Weight History
(kg) of exposure
4.7 i9.9
± ±
4.8 i9.3
Barium
mg I/mI)
mg I/mI)
2i
22
1 2/9
1 5/7
18 9/9
20
20
12
i
2
5.4 19.2
±
5.8
±
16.6
6
3.5
±
4.5
i .2
±
15.5
±
14.9
4.7
±
3.1 5.5
to con-
trast medium (V/N) Associated risk factor(s) including
0
lohexol (i 80
sensitivity
to ller-
gens or contrast (V/N)
medium
8/i 3
12/9
No significant difference in the volume of contrast material administered was found between the three groups in the iohexol/barium study (p = .63i). The volumes given were 5.2 ± 5.9 mb/kg (iohexol i 80 mg I/mb), 7.0 ± 7.0 (iohexol 300 mg I/mb), and 6.5 ± 3.3 mI/kg (barium). The difference in the dose per kilogram between the iohexol i 80 mg b/mb groups in the iohexob/barium study (5.2 ± 5.9 mb/kg) and in the iohexob-only study (9.2 ± 5.6 mI/kg) was statistically significant (p = .048). Comparing blood pressure and pulse nate recordings before and after contrast administration for patients in the iohexol/ barium study, we noted that nine patients had systolic blood pressure changes of 30 mm Hg or greater; these systolic blood pressure changes ranged from -38 to +63 mm Hg. Three patients had diastolic blood pressure changes of 30 mm Hg on greaten; these changes ranged from +30 to +38 mm Hg. Twenty-one patients had pulse rate changes of 30 beats pen minute or greater; these changes ranged from -64 to +98 beats per minute. Most of the changes represented increases from relatively low baseline recordings or decreases from relatively high baseline recordings. Most of the changes were transient and many were thought to be due to an agitated state of the patient before or when the vital sign measurements were taken. No difference in the changes of blood pressure and pulse rate was seen between the three groups of patients. No clinical adverse effects were ascribed to the vital sign changes, and no child required treatment on the basis of changes in vital signs. Adverse event information is summarized in Table 2. Eleven patients from the iohexol i 80 mg b/mb group had a total of i 7 adverse events, and nine patients from the iohexol 300 mg 1/ ml group had a total of 12 adverse events. One patient from the barium group had a single adverse event. The most common adverse event was mild to moderate diarrhea. Overall none of the adverse events were serious or life threatening and all were followed up until they resolved. Allocation of a patient to a high-risk subgroup did not predict an adverse event, as adverse events were detected more frequently in the bow-risk group than in the high-risk subgroup.
7/i 4
6/i 6
9/12
4/i 4
16/6
TABLE
2: Summary
i5/3
of Adverse
Iohexol(i80 mg
No. of patients Abdominal
pain
I/mI)
Events
in lohexob/Barium
Iohexol(300 mg
I/mI)
20
22
1
0 0 0 0 0 1 1
10
Fever Nausea
i i
Urticaria Vomiting
3
0 8 2 2 0 0
17
12
a
B a r tu m
20
Diarrhea
Totala
Study
i
Barium vs iohexol 180 is significant (p .005); barium vs iohexol 300 is (p = .003); iohexol 180 vs iohexol 300 is not significant (p = .75).
significant
The results of nadiobogic evaluation of the image quality for the various contrast agents are given in Tables 3-6. Tables 3, 4, and 5 give the analysis for nadiobogic visualization, mucosal coating, and contrast density for the three contrast agents used in the iohexol/banium study. The results are given separately for the duodenum, esophagus, stomach, small bowel, and large bowel. There are 64 separate evaluations for iohexob i 80 mg I/mI, 63 for iohexol 300 mg b/mb, and 78 barium assessments for individual organs. Of these, only six with iohexol 1 80 mg I/mb, seven with iohexol 300 mg b/mb, and three with barium were considered nondiagnostic (poor rating on radiographic visualization). With regard to mucosab coating, the ratings were good on excellent for 52 (80%) of iohexol 1 80 mg I/mb, 57 (90%) of iohexob 300 mg b/mI, and 77 (99%) of barium evaluations. Contrast density was considered optimal in 58 (9i %) of iohexol i 80 mg I/mI, 57 (90%) of iohexol 300 mg I/mb, and 73 (94%) Of barium evaluations. Table 6 gives similar data for iohexol 1 80 mg b/mI for the iohexol-onby study. Three of 53 iohexol 180 mg I/mI assessments were nondiagnostic (poor radiographic visualization). Mucosal coating was good or excellent in 50 cases (94%). Density was considered optimal in 49 evaluations (92%).
348
COHEN
TABLE
3: Radiologic
Efficacy
by Anatomic
Site for Barium
ET AL.
in Barium/lohexol
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Radio logic Visualization Site
Poor
M ucosal
lent
Diag-
2 0
6 3
13 17
21 20
90 100
Stomach
0
i 2
9
2i
Small Bowel Large Bowel
1 0
5 2
7 i
i3 3
Good
TABLE
+
Poor
Coating Percent
Ecel-
Good
Total
Diag-
nostica
Not Dense Enough
Optimal (%)
Dense
20 (95) 19 (95)
0 i (5)
Too
(%)
7 8
2i 20
95 100
(%) 1 (5) 0
16
5
2i
1 00
0
19 (90)
2 (10)
4 2
9 1
13 3
100 100
1 (7) 0
12 (93) 3 (i 00)
0 0
i 0
i3 12
i 00
0
92 i 00
0 0
1991
Density
nostica
Esophagus
Duodenum
a
Total
February
Study
Percent
Excel-
Good
AJA:156,
excellent.
4: Radiobogic
Efficacy
by Anatomic Radiologic
Site for lohexol
(i80
mg b/mb) in bohexol/Barium
Visualization
Mucosal
Study
Coating
Density
Not
Site Poor
Excel-
Good
Total
Percent
Diagnostica
Poor
Good
Excel-
lent
Total
Percent
Dense
Diagnostica
Enough
Optimal
(%)
(%)
a
Duodenum
2
13
1
i 6
88
5
i i
0
i6
69
2 (1 3)
i 4 (88)
Esophagus
i
14
4
19
95
2
i7
0
i9
89
2(u)
i7(89)
Stomach
0
14
4
i8
1 00
2
14
2
18
89
0
i 8 (i00)
Small Bowel Large Bowel
3 0
4 2
i i
8 3
63 1 00
3 0
4 3
i 0
8 3
63 i 00
Good
TABLE
+
2 (25) 0
6 (75) 3 (i 00)
excellent.
5: Radiobogic
Efficacy
by Anatomic Radiologic
Site for lohexob (300
mg I/mb) in bohexob/Barium
Visualization
Mucosal
Study
Coating
Site Poor
Good
Excel-
Total
Diagnostica Percent
Poor
Good
Excel-
Total
Density Not Dense Enough
Percent Diagnostica
Optimal
(%)
(%)
a
Duodenum
i
i 0
Esophagus
0
iO
Stomach Small Bowel Large Bowel
i 5 0
Good
TABLE
+
9 5 1
3 7
14 17
93 iOO
i 0
i 1 14
2 3
14 i7
93 100
i (7) 0
i 3 (93) i7(iOO)
5 2 4
15 12 5
93 60 i 00
0 4 i
11 6 0
4 2 4
i5 12 5
100 67 80
i (7) 4 (34) 0
i 4 (93) 8 (65) 5 (i 00)
excellent.
6: Radiologic
Efficacy
by Anatomic Radiologic
Site for lohexol
Good
in lohexol-Only
Visualization
Site
Poor
(180 mg I/mI)
Excel-
Total
Mucosal
Percent Diagnostica
Poor
Good
Excellent
Study Coating
Density
Total
Not Dense Enough
Percent Diagnostica
Optimal
(%)
(%)
S
Duodenum
i
8
4
i3
92
i
i i
i
13
92
i (8)
i 2 (92)
Esophagus Stomach Small Bowel
0 0 2
7 8
2 3 1
9 i4 1i
iOO iOO 82
0 0 2
8 14 9
i 0 0
9 i4 i1
iOO iOO 82
i (ii) 0 2 (1 8)
8(89) i4(iOO) 9 (82)
Large Bowel
0
3
3
6
1 00
0
5
i
6
100
0
Good
+
ii
6 (i 00)
excellent.
We evaluated the overall nadiobogic efficacy for each contrast agent. In the iohexol/banium study, barium was rated as excellent in i 2 cases and good in 10 cases; iohexol i 80 mg b/mb was rated as excellent in four cases, good in i 4 cases,
and poor in three cases; excellent in seven cases, cases. In the iohexol-only rated
as excellent
in six
iohexol 300 mg I/mI was rated as good in 1 2 cases, and poor in two study, iohexol i 80 mg b/mI was cases
and
good
in i 2 cases.
These
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AJR:156,
February
1991
PEDIATRIC
Gb STUDIES:
IOHEXOL
VS
349
BARIUM
data are for the radiologist’s impression of the overall quality of the entire study, but are not broken down by anatomic region. No statistical significant difference among the contrast media was found in the iohexol/barium study (p = .21 5) with regard to diagnostic (good + excellent) vs nondiagnostic (poor) assessments. However, when the individual classifications of overall quality (poor, good, excellent) are considered, a significant (p = .024) difference is seen among the contrast media owing to the greaten frequency of excellent assessments in the barium group relative to the iohexol i80 mg I/mI group. No significant difference was observed between the iohexol 180 and 300 mg b/mb groups when individual assessments of specific organs were compared in the iohexol/banium study (Table 2).
iohexol/barium study. For overall radiobogic efficacy, three of 2i studies with iohexob i80 mg b/mI in the iohexol/banium study were rated as poor, whereas no studies with this concentration were rated as poor for the iohexol-only study. Two reasons are believed to account for this difference. The patients receiving iohexol i80 mg I/mb in the iohexol-only study received a greater volume of contrast material pen kilogram of body weight (9.2 ± 5.6 ml) than did those patients in the iohexol/banium study (5.2 ± 5.9 mI/kg). Second, the age and weight of the patients in the iohexol-only study are very different from those of patients in the iohexol/banium study (Table i). This is because many of the clinical conditions for which barium is contraindicated exist in the newborn. In the small patients in the iohexol-only study, the lower body weight may result in less scattering of the X-ray beam with less boss of contrast on the radiograph. The concentration of
Discussion
iodine
In selected clinical situations, bow-osmolality water-soluble contrast agents have definite advantages over other contrast agents for examination of the gastrointestinal tract in children [i]. Early attempts to achieve low osmolabity involved dilution of high-osmolality contrast agents with resultant very low iodine concentrations [1 5]. For the past i 0 years, metnizamide has been used in almost isotonic solutions and with an iodine concentration of 1 80 mg I/mb to achieve good-quality images for the diagnosis of a variety of disorders in children, including bowel perforation [6-8] and necrotizing enterocolitis [4-i 0]. Unfortunately metnizamide is expensive. bohexob is similar to metrizamide, but less costly. Like metrizamide, it is extremely stable in bowel secretions [i 6] and has virtually no absorption from the normal bowel [1 6, 17]. Previous reports suggest that iohexol will have clinical usefulness similar to that of metrizamide in the intestinal tract, but unfortunately these reports do not include comparative double-blind evaluations of these agents [i 1 -i 3, i 8]. Evaluation of the radiobogic visualization, mucosal coating, and density of the contrast agent showed that barium was the preferred contrast agent for each of these evaluations, although the difference between barium and iohexol was not great. The particulate nature of the barium probably accounts for its preference for mucosab coating. The greaten attenuation of the X-ray beam by barium probably accounts for the fewer ratings of poor visualization with barium than with iohexol. The radiologists’ overall rating of radiobogic efficacy for each study showed that none of the barium studies was rated as poor, whereas five of the iohexol studies were assessed as poor. It should, however, be noted that 37 of the iohexol examinations in the iohexob/banium study were rated as good or excellent. Barium had more ratings of excellent than iohexob had. In summary, the results of the iohexob/banium study indicate that radiologic visualization with iohexol is good, but if the use of barium was not contraindicated, barium is the preferred agent. The iohexol-onby study evaluated iohexol i 80 mg b/mb in an open manner in patients for whom barium was contraindicated. A comparison of Table 4 (iohexob i 80 mg I/mb in the iohexol/barium study) and Table 6 (iohexob i 80 mg b/mb in the iohexol-only study) indicates fewer poor evaluations with this concentration of iohexob in the iohexol-only study than in the
degradation from scatter is greater in the larger patients. Both iohexol and barium were safe agents in that no major contrast reactions requiring therapeutic intervention on hospitalization were identified in either group. Table 2 shows, however, a much higher frequency of minor side effects with iohexol than with barium. In the iohexol/banium study, only one minor reaction occurred with barium, whereas 29 neactions occurred with iohexol. The frequency of these minor reactions did not correlate with the presence of high-risk factors in the patients’ histories. Of these adverse events, diarrhea was by far the commonest. The diarrhea was slightly more common in the patients with the bower concentration of iohexol. Ten patients receiving iohexol i 80 mg b/mI had diarrhea, compared with eight patients receiving iohexol 300 mg I/mI. The osmolality of the i 80 mg b/mb iohexol concentration is 408 mOsm/I and that of the 300 mg I/mb iohexol is 798 mOsm/I. Although the differences in the frequency of diarrhea are not statistically significant, they do raise the possibility that the toxic effect of iohexol causing diarrhea may not be purely an osmotic effect but might be due to some other irritating effect of this agent on the bowel. The osmolality of iohexob i 80 mg I/mb is only about 35% greaten than that of normal blood, and the high frequency of diarrhea is somewhat surprising if one postulates that the diarrhea is due purely to an osmotic effect of the contrast agent. Unfortunately a review of the literature does not provide additional answers. In three European studies with iohexob, a combined total of 1 12 patients had no episodes of diarrhea [19]. In another study that used iohexol 350 mg b/mI in adults, diarrhea was reported as a common event [20]. In i i fit adults, 150 ml of iohexol 350 mg b/mb caused diarrhea in 1 0 patients [2i ]. Finally, in a study of i 1 5 patients receiving either iohexol, iopamidol, or ioxaglate, no evidence of toxicity was reported. The difference in frequency of diarrhea in patients receiving iohexol as compared with the patients receiving barium is highly significant. Although many of our patients were receiving concomitant medication, the medications received did not differ among the three groups of patients, and we therefore believe that the diarrhea is a result of the iohexol and not of the concomitant medication. With regard to vital signs, the difference between the changes in blood pressure and pulse rate observed in the
is the
same
for each
group
of patients,
but
the
image
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350
COHEN
three groups was not statistically significant, and we believe that all of these changes can be accounted for by variations in the calmness or agitation of the patients when the readings were made. In summary, iohexob can be effectively used as a contrast agent in the gastrointestinal tract. The frequency of side effects is greaten than that with barium, but these side effects are mild. Although iohexob is not as good as barium for bowel visualization, it should provide an excellent substitute for the more expensive metrizamide for those patients in whom barium is relatively on absolutely contraindicated. The radiologists’ perception of image quality with iohexob is better in smaller than in larger patients. These data have been submitted to the Food and Drug Administration for approval to label iohexob “for oral use in the gastrointestinal tract in children.” Approval has not yet been obtained.
1 . Cohen MD. Choosing contrast media for the evaluation of the gastrointestinal tract of neonates and infants. Radiology 1987:162:447-456 2. Cohen M, Smith WL, Smith JA, Gresham EL, Schreiner A, Lemons J. The
use of metrizamide
(Amipaque)
to visualize the gastrointestinal
tract in
report. Clin Radiol 1980;31 :635-641 visualization of the gastrointestinal tract with metriz-
amide. Radiology 1982;i43:327-328 4. Cohen MD, Smith JA, Slabaugh RD, Rust RJ. Neonatal necrotizing enterocolitis shown by oral metrizamide (Amipaque). AJR 1982;138: ioi 9-i 023 5. Cohen MD, 5chreiner A, Grosfeld J, Weber T, Lemons J, Jansen R. A new look at the neonatal bowel: contrast studies with metrizamide (Amipaque). J Pediatr Surg 1983:18:442-448
AJR:i56,
6. Cohen MD, Weber TA, Grosfeld JL. Bowel perforation
February 1991
in the newbom:
diagnosis with metrizamide. Radiology 1984:150:65-69 7. Belt T, Cohen MD. Metrizamide evaluation of the esophagus AJR 1984;143:367-369
in infants.
8. Cohen MD, Jansen A, Lemons J, Schreiner A. Evaluation of the gasless abdomen in the newbom and young infant with metrizamide. AJR 1984:142:393-396
9. Johansen JG. Assessment of a non-ionic contrast medium the gastrointestinal tract. Invest Radiol 1978:13:523-527
(Amipaque)
in
1 0. Keller MS. Chawla HS. Neonatal metrizamide gastrointestinal series in suspected necrotizing enterocolitis. Am J Dis Child 1985;139:7i3-7i6 1 1 . Clarke EA, Dutton NE. Use of iohexol in the early determination of gastrointestinal perforation. J Pediatr Surg 1988;23: 1027-1 028 12. Brick SH, Caroline DE, Lev-Toaff AS, Friedman AC, Grumbach K, Radecki PD. Esophageal disruption: evaluation with iohexol esophagography. Radiology I988;169:141-143 13. Ratcliffe JF. The use of ioxaglate in the paediatric gastrointestinal tract: a report of 25 cases. Clin Radiol 1983;34:579-583 14. Ratcliffe JF. The use of low osmolality water soluble (LOWS) contrast media in the pediatric gastro-intestinal tract: a report of 1 i5 examinations. Pediatr Radiol 1986:16:47-52 15. Kuhns LA, Kanellitsas C. Use of isotonic water-soluble contrast agents for
gastrointestinal 16. Schwartzentruber
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