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Absorption of Contrast Medium During

ERCP
R.A. SABLE, MD, W.S. ROSENTHAL, MD, J. SIEGEL, MD, R. HO, MD,
and R.H. JANKOWSKI, RN, BS

In order to assess systemic absorption, serum diatrizoate levels were measured in 25


patients requiring endoscopic retrograde cholangiopancreatography (ERCP). Urinary
diatrizoate was measured in the urine of seven o f these. In five additional patients,
diatriZoate was instilled into the duodenum during endoscopy. Blood was drawn before
and after completion o f the procedure in all patients and at intervals from 2 to 24 hr in
nine. Eighteen-hour urine collections were obtained from seven patients. Increases in
serum diatrizoate concentration were 7.10 ~g/ml +- 3.01 (mean +- SE) in the duodenal-
instillation patients, 230.68 +- 53.24 ps in 9 patients in whom only the pancreatic duct
was visualized, 7.83 +-- 1.05 p.g/ml in three patients in whom only the bile duct was
visualized, and 77.67 +- 28.22 ~g/ml in 13 patients in whom both ducts were visualized.
The mean total urinary excretion of diatrizoate was 3.05 +-- 0.98 g of diatrizoate.
Endoscopists performing ERCP should be aware of the likelihood of systemic absorption
and the possibility of reactions to iodinated Contrast materials in sensitive patients.

Hypersensitivity to iodized contrast media may the clinical disease states which may predispose to
preclude procedures such as intravenous cholangi- increased absorption, we have measured meglu-
ography where visualization of the biliary tree is mine diatrizoate levels in serum and urine in pa-
important for diagnostic and therapeutic purposes. tients undergoing ERCP.
Endoscopic retrograde cholangiopancreatography
(ERCP) with direct instillation of contrast material MATERIALS AND METHODS
into the biliary and pancreatic ducts provides an
alternative method of obtaining this information. The study included 25 patients, who required ERCP as
part of the evaluation of symptoms referable to diseases
However, pyelography (Figure 1), indicating ab-
of the biliary tract or pancreas. There were 12 males and
sorption of organic iodide, has been reported during 13 females, whose age ranged from 29 to 73. They were
ERCP variably ranging from 0.07% of 10,000 cases subdivided as follows: group A consisted of 9 patients
(1) to as many as 35% of 27 cases (2). This indicates with demonstration of the pancreatic duct only, group B
that substantial absorption of contrast material may contained three patients with demonstration of the bile
duct only, and group C comprised 13 patients in whom
occur. To evaluate the frequency and extent of
both ducts were demonstrated. In addition, five patients
absorption of this contrast material and to correlate were studied who had upper gastrointestinal endoscopy
for standard indications, but in whom no pathology was
found (group D). Group D included two male and three
Manuscript received October 26, 1982; revised manuscript female patients, ranging in age from 26 to 88. In the latter,
received March 22, 1983; accepted May 6, 1983.
From the Sarah C. Upham Section of Gastroenterology,
contraSt medium was instilled into the duodenum to
Department of Medicine, New York Medical College, Westches- evaluate intestinal absorption of diatrizoate. Table 1
ter County Medical Center, Valhalla, New York 10595. contains diagnostic data and separates patients on the
Address for reprint requests'. Dr. W.S. Rosenthal, Sarah C. basis of which duct was demonstrated during the study.
Upham Section of Gastroenterology, New York Medical Col- Informed consent was Obtained from all patients partici-
lege, Valhalla, New York 10595. pating in the study.

Digestive Diseases and Sciences, Vol. 28, No. 9 (September 1983) 801
0163-2116/83/0900-0801503.00/1 9 1983 Digestive Disease Systems, Inc.
,SABLE ET AL

Fig 1. X-ray taken during ERCP showing the endoscope, a filled pancreatic duct, and the visualization of a calyx in the right kidney.
The arrow points to the renal calyx.

Meg!umine diatrizoate (60%) was instilled into all pa- dures such as angiography or intravenous pyelogra-
tients in amounts sufficient to achieve visualization of phy during which iodinated contrast material was
either or both ducts. This usually amounted to approxi- administered. N o relationship was found between
mately 30 ml (18 g), but varied considerably. Neverthe-
less, that specific amount of contrast was instilled into the the clinical diagnosis and the rise in serum diatri-
duodenum of group D individuals. Ten milliliters of blood zoate concentration. H o w e v e r , there did appear to
was obtained prior to the endoscopic procedure and be a definite relationship between the level of serum
immediately after completion of the study in all patients. diatrizoate and the success in demonstrating specif-
In addition blood was Obtained at intervals until 24 hr ic ducts (Table 1).
after the procedure in nine patients. To assess total
absorption, 18-hr Urine collections were obtained in seven In group B patients, in whom only the bile duct
patients. Serum and urine Specimens were frozen imme- was visualized, or group C, in whom both the bile
diately and diatrizoate content was determined later using duct and pancreatic duct were opacified, there was
methods which are standard in the pharmaceutical indus2 no significant difference in diatrizoate levels at-
try (3). Statistical analysis was performed using Student's tained when c o m p a r e d to group D patients (Figure
t test for paired and unpaired observations (4).
2). H o w e v e r , in group A patients, in Whom only the
pancreatic duct was visualized, the mean increase
RESULTS
in serum diatrizoate levels between the pre- and
The serum concentrations of diatrizoate for each p o s t e n d o s c o p y samples was 234.3 +- 53.1 p.g/ml
patient are shown in Table 1. The p r e e n d o s c o p y (Figure 2). This was highly significant (P < 0.005)
serum value represents the blank. In some in- when compared to observations in group D individ-
stances minimal elevations may reflect prior proce- uals. The change in serum diatrizoate in group D

802 Digestive Diseases and Sciences, Vol. 28, No. 9 (September 1983)
ABSORPTION OF CONTRAST MEDIUM

TABLE 1. CHANGE IN SERUM DIATRIZOATE LEVEL FOLLOWING ADMINISTRATION OF CONTRAST BY ENDOSCOPIC ROUTE

Diatrizoate serum level (txg/ml)


Patient Diagnosis Preendoscopy Postendoscopy

Group A: Pancreatic duct visualized


1 Pancreatic cancer 0.9 62.2
2 Pancreatic cancer 5.9 216.1
3 Cirrhosis of liver 0.4 63.3
4 Cirrhosis of liver 0.6 209.4
5 Cancer of gallbladder 11.8 77.9
6 Cirrhosis of liver 0.4 356.0
7 Abdominal pain 4.0 522.1
8 Abdominal pain 3.3 221.3
9 Cholelithiasis 5.0 380.1
Mean (-+ SE) 3.6 (-+1.2)* 234.3 (-+53.1)*
Group B: Bile duct visualized
10 Stricture right hepatic duct 0.7 10.2
11 Abdominal pain 0.4 8.5
12 Abdominal pain 0.6 6.5
Mean (• 0.6 (-+0.1)~ 8.4 ( - 1.1)?
Group C: Both ducts visualized
13 Pancreatic cancer 1.3 60.7
14 Alcoholic with cholestasis 4.5 31.6
15 Alcoholic with choIestasis 1.9 78.2
16 Alcoholic with cholestasis 0.4 8.8
17 Alcoholic with cholestasis 0.9 19.1
18 Metastatic carcinoma 0.6 40.5
19 Cirrhosis of liver 0.6 360.0
20 Cholestasis 0.7 38.8
21 Papillary stenosis 11.1 31.8
22 Abdominal pain 6.6 23.4
23 Cholelithiasis 3.3 215.9
24 Cholelithiasis 0.4 15.5
25 Cholelithiasis 0.9 118.6
Mean (-+SE) 2.5 (--+0.9)? 80.2 (•
Group D: Duodenal contrast instillation
1 No endoscopic pathology 2.9 7.5
2 No endoscopic pathology 0.6 0.9
3 No endoscopic pathology 1.2 10.7
4 No endoscopic pathology 0.6 18.2
5 No endoscopic pathology 2.4 5.9
Mean (--+SE) 1.5 (+0.5)~ 8.6 (+2.9)$
*Difference significant (P < 0.005).
?Difference significant (P < 0.01).
~:Difference significant (P < 0.05).

patients was small, but significant (P < 0.05). The to parallel the serum concentration. No patient
mean preendoscopy serum level was 1.5 fxg/ml developed clinical pancreatitis. Despite a history of
rising to 8.6 Ixg/ml following endoscopy (Figure 2). previQus hypersensitivity to intravenous contrast
This is consistent with minimal absorption of con- media in two patients, no allergic manifestations
trast medium from the intestine, as well as the bile were observed among the individuals studied. In
duct or pancreatic duct. the two patients with a history of hypersensitivity,
The urine studies demonstrated that large serum diatrizoate levels of 215 and ! 18 txg/ml were
amounts of diatrizoate were excreted in five of the noted.
seven patients studied. In these five patients, this Samples obtained between 2 and 24 hr indicated
was equal to a mean of 4.1 +-_ 2.3 g which would be that the peak serum value observed occurred at the
approximately 22% of the administered dose (18 g). end of the endoscopic procedure.
Lower concentrations were present in the urine of
DISCUSSION
the other patients studied in whom the serum con-
centrations were also low. Thus, as might be ex- ERCP is a relatively safe method of examining
pected, the urinary excretion of diatrizoate tended the biliary tree with iodized radiographic contrast

Digestive Diseases and Sciences, Vol. 28, No. 9 (September 1983) 803
SABLE ET AL

Diotr/zoo/e ins/riled into..


I000
Pancreatic Bile Duct Both Ducts Duodenum
Duct

I00

13
E
13n
"4
o
o o
o
...J
o
10
o
_r []
[]

O &
~5
o
E
0
0

o
1.0 0
KEY
17
oo .~_ Mean:l: I S.E.

&9 9 o13 Contrast injected into:


9 Poncreotic Duct
9 Bite Duct
o Both Ducts
o Duodenum

Pre / Post Pre / Post Pre / Post Pre / Post


instillation Status
Fig 2. Effect on serum levels of instillation of contrast medium into bile ducts and
pancreatic ducts, individually and together, during ERCP compared to the effect of
direct instillation into the duodenum.

media. In a survey of 10,000 ERCP procedures (1), trast material which occurred during the perform-
51 drug reactions (0.5%) were found, but only three ance of ERCP. It should be emphasized that high
were attributed to the contrast medium (0.03% of levels of serum diatrizoate were achieved without
total). This can be compared with a 10% incidence reaction in two patients in whom there was a prior
of reactions associated with intravenous cholangi- history of hypersensitivity to aqueous radiographic
ography (5). The present study, however, demon- contrast media (hives in both).
strated that no reaction to the media occurred in While no pyelograms were noted in this series, 19
any patient, despite significant absorption of con- of 25 patients demonstrated an elevation of serum

804 Digestive Diseases and Sciences, Vol. 28, No. 9 (September 1983)
ABSORPTION OF CONTRAST MEDIUM

diatrizoate levels on completion of the procedure pressure into the biliary tree of rats and demonstrat-
which was higher than the highest value seen in ed disruption of hepatocytes and distribution of
group D. In the overall study group of patients, these markers in hepatocytes, sinusoids, and the
there was visualization of the pancreatic duct in space of Disse. This undoubtedly represents a po-
nine, while in another 13 patients, visualization of tential route for materials injected into the biliary
both the pancreatic and bile ducts was achieved tree to reach the systemic circulation, if the force of
(Table 1). Based on this observation, we conclude injection is sufficiently high.
that absorPtion of the medium occurs mainly via the The low incidence of reactions to contrast media
pancreatic duct. In our study, repeated attempts to during ERCP is probably related to the slow rate of
selectively opacify the biliary tree after demonstra- absorption when compared with direct intravenous
tion of the pancreatic duct probably resulted in injection. Saltzman and Sundstrum (11) showed
repeated filling of the pancreatic duct system and that the degree of fall in blood pressure and increase
thus promoted parenteral absorPtion of the media. in pulse rate was directly associated with the rate of
With this in mind, review of the available films did intravenous injection of water soluble organic io-
not reveal overt radiological evidence of overfilling. dide containing contrast agents. Busfeld et al (12),
The increases in serum diatrizoate were significant- using a similar agent, also reported increased toxici-
ly less when simultaneous filling of both systems ty associated with increasing rate of intravenous
occurred. In the three patients in whom only the injection.
bile duct was visualized, there was no difference in Similarly, in clinically performed intravenous
contrast level rise from that demonstrated after cholangiograms, the incidence of reaction is also
simple instillation of contrast into the duodenum. related to the time rate of the injection of contrast
Considerable experimental efforts have been ex- (5). If the contrast is injected over a 2-min period,
pended with respect to the mechanism of absorp- the incidence of reactions was 13%; injections last-
tion of materials from the pancreatic duct. Bognel et ing 3-10 min produced an 11% reaction rate, and
al (6) demonstrated in their study in dogs that dye injections taking 11 min or longer produced a 7%
injected into the main pancreatic duct was not reaction rate.
recoverable in lymph collected from the thoracic In light of our findings that there is a significant
duct. Their conclusion was that absorption of con- absorption of diatrizoate with ERCP, endoscopists
trast media is more likely through acinar-portal should be prepared for reactions to contrast, al-
pathways and not via the lymphatics. Pietri et al (7) though the incidence is small.
have shown that retrograde injection of contrast
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Digestive Diseases and Sciences, Vol. 28, No. 9 (September 1983) 805
SABLE ET AL

tion following experimental ERCP. Invest Radiol 14:493- tin in experimental animals. A combined light and electron
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806 Digestive Diseases and Sciences, Vol. 28, No. 9 (September 1983)

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