Three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective analysis of feasibility and adverse reaction to contrast material.
© Persson et al; licensee BioMed Central Ltd. 2006
Received: 30 August 2005
Accepted: 22 April 2006
Published: 22 April 2006
Computed Tomography Cholangiography (CTC) is a fast and widely available alternative technique to visualise hepatobiliary disease in patients with an inconclusive ultrasound when MRI cannot be performed. The method has previously been relatively unknown and sparsely used, due to concerns about adverse reactions and about image quality in patients with impaired hepatic function and thus reduced contrast excretion. In this retrospective study, the feasibility and the frequency of adverse reactions of CTC when using a drip infusion scheme based on bilirubin levels were evaluated.
The medical records of patients who had undergone upper abdominal spiral CT with subsequent three-dimensional rendering of the biliary tract by means of CTC during seven years were retrospectively reviewed regarding serum bilirubin concentration, adverse reaction and presence of visible contrast media in the bile ducts at CT examination. In total, 153 consecutive examinations in 142 patients were reviewed.
Contrast media was observed in the bile ducts at 144 examinations. In 110 examinations, the infusion time had been recorded in the medical records. Among these, 42 examinations had an elevated bilirubin value (>19 umol/L). There were nine patients without contrast excretion; 3 of which had a normal bilirubin value and 6 had an elevated value (25–133 umol/L). Two of the 153 examinations were inconclusive. One subject (0.7%) experienced a minor adverse reaction – a pricking sensation in the face. No other adverse effects were noted.
We conclude that drip infusion CTC with an infusion rate of the biliary contrast agent iotroxate governed by the serum bilirubin value is a feasible and safe alternative to MRC in patients with and without impaired biliary excretion.
In this retrospective study the feasibility and the frequency of adverse reactions when using a drip infusion scheme based on bilirubin levels has been evaluated.
For diagnosis of hepatobiliary disease, ultrasound and MR cholangiography (MRC) are most frequently used. Endoscopic Retrograde Cholangiography (ERC) is often regarded as the gold standard for visualising biliary disease. The latter modality is invasive, user-dependent and may induce pancreatitis. It should therefore not be performed in patients where intervention is less certain. Ultrasound, on the other hand, is easily tolerated by the patients and cost effective. The modality is, however, user-dependent and the captured images are not easily understood by clinicians. MRC is superior in visualising the biliary system, and the images are appreciated by the surgeons at surgical planning. It does not require any contrast agent to visualise the bile ducts, and dilatation and gallstones in the common bile duct are easily detected [1–3]. Unfortunately, MRC cannot be performed in all patients and hospitals due to limited availability of MRI or due to contraindications. MRC is also often inconclusive in patients with air in the biliary system, e.g. after papillotomy or liver surgery with entero-hepatic anastomoses (such as Whipple's operation and Billroth 2). Surgical clips after cholecystectomy may also give artefacts mimicking a ductal cancer or a stone [4, 5]. An alternative non-invasive method to ultrasound and MRC is therefore required.
Computed Tomography Cholangiography (CTC) is a fast and widely available technique to visualise hepatobiliary disease. Without contrast administration, multi detector CT has been reported to have a sensitivity of 65%–88% and a specificity of 84%–97% to detect gallstones [6, 7]. Techniques to improve the sensitivity and specificity by administering biliary contrast media orally  or intravenously [9, 10] have been developed, but are not wide-spread. Possible explanations for infrequent use of CTC might be the low resolution of single detector helical CT and reports of an unacceptable high number of adverse events after injection of meglumine iotroxate . With the development of multidetector CT, the resolution of CTC exceeds that of MR. The number of adverse reactions with biliary contrast media has probably diminished by infusing the contrast media instead of injecting.
The aim of this retrospective study was to evaluate prolonged drip infusion CT cholangiography (CTC) in patients with suspected obstructive biliary disease with respect to both feasibility and rate of adverse reactions after administration of the biliary contrast agent (iotroxate).
This is a retrospective study in 142 consecutive patients (68 men and 74 women, mean age 69 years, range 24 – 95 years) referred for investigation of biliary disease during the period from January 1996 to January 2003. After approval by the ethics committee for the region, the medical records of all patients were retrospectively reviewed regarding bilirubin level, infusion time and adverse events. Adverse events were defined as any signs of reaction to contrast media that occurred after the injection, such as anaphylaxis, urticaria and respiratory distress.
Administration of contrast media
The infusion rate of iotroxate (Biliscopin®) was governed by the bilirubin level prior to the investigation. The same total amount of Iodine (5 g) was given to all patients.
CT acquisition parameters
Type of scanner
Number of examinations
1 × 5.0 mm
4 × 2.5 mm
16 × 0.75 mm
Evaluation of contrast media excretion
The attenuation in choledochus and liver was obtained retrospectively by measurement in the restored digital images in all examinations with bilirubin >19 μmol/L (n = 42), as well as in 67 individuals also described in another study , 19 of the latter with bilirubin >19 μmol/L. In total, attenuation values from 90 (= 42 + 67 - 19) patients were obtained.
Review of literature
A MEDLINE search was performed for all clinical studies in English published during the period 1975–2004 concerning iotroxate, using the words "Biliscopin" or "iotroxate". All articles were reviewed for reports regarding adverse events. The pooled frequency of adverse events was calculated for all articles with a number of patients >100 where the contrast had been infused for 30 minutes or more.
Data are given as mean (± standard deviation). Frequencies are given with their 95% confidence interval, computed with normal approximation.
Out of 153 examinations performed in 142 patients, one subject experienced a minor reaction (pricking sensation in the face) following the administration of 70 ml of contrast. In this patient, the pre-exam bilirubin value was normal (11 μmol/L) and the planned infusion time was 60 minutes. Four weeks later, the same patient successfully underwent a repeated CT cholangiography using the same infusion rate without any adverse reactions. In the other 141 patients (151 examinations), no adverse reaction was noted in the medical records. Thus, the observed frequency of adverse reactions in this material was 1/153 (0.65%). Of the 153 examinations, 10 were performed in out-patients. These patients normally stay in the radiology department one hour after the contrast injection has been completed. Due to the retrospective nature of this study, late mild adverse advents may not have been recorded in these 10 patients. More severe adverse reactions such as a skin rash, itches, etc. are, however, usually reported to the hospital by the patients and according to the routines of the hospital, adverse reactions are always noted in the medical records after an X-ray examination. The hospital is the only one in the district and no notes could be found about adverse advents in the patients' files (files from departments of radiology, surgery and internal medicine were reviewed).
The bilirubin value, infusion time and final diagnosis in the nine cases where no secretion of contrast media was observed at DIC-CT.
Bilirubin value, μmol/L
Infusion time, minutes
Reported findings in medical records, final diagnosis
Reported findings at DIC-CT
Hepatitis Type B1
wide bile duct
Intraductal stone in choledochus and pancreatitis 7,2,6
wide bile duct
Concrememt in choledochus1,2,3,6,
Concrement in choledochus, Total occlusion and Klatskin tumour5,7
Intraductal stone, tumour
Distal stenosis in choledochus and pancreatitis 4,5,7
Total occlusion in choledochus, pancreas tumour 2,3
wide bile duct
Post operative cholangitis/cholecystitis with bile fistula and leakage1,6,7
The remaining 4 patients had hepatitis, pancreatitis, cholangitis or cholecystitis.
Review of literature
Published studies on the frequency of adverse reactions at infusion of iotroxate at intravenous cholangiography. Included are all studies with at least 100 patients using an infusion time of at least 30 min. The severity of the reactions is graded as reported. The number in superscript denotes the corresponding reference.
No. of Patients
11 A (1.0%)
Frequency (95% confidence limits)
The lack of excretion may also constitute valuable information. Patients without excretion are likely to have either a total occlusion of the main bile duct/choledochus or severely impaired hepatocyte function. The bilirubin concentration, if not already considerably elevated, is likely to increase in these patients. In this study, the lack of excretion could be explained by the final diagnosis in all patients (Table 3).
The protein-binding characteristics essential for biliary contrast media increase the risk of adverse reactions [11, 15]. In a previously published review of the literature on the frequency of adverse reactions in examinations with short injection time (<10 min), the pooled number of adverse events was three times higher (16% vs. 5%) than after infusion (>30 min) of the same amount of contrast media . The frequency of adverse events of iotroxate (Biliscopin®) at infusion has been reported to be as high as 3.4%, with a pooled frequency of 1.9% (Table 4). It has been proposed that the tolerance of intravenous biliary contrast media is improved when a slow infusion technique is used (up to one hour of infusion) [16, 17]. Our study supports this proposal, as there was only one adverse reaction, which was mild, in 142 patients and 153 examinations (0.65%).
After an inconclusive ultrasound examination, MRC has the advantage of not exposing the patient to radiation and contrast media. On the other hand, in many clinical situations the availability of MRI examinations with short notice is limited. The sensitivity and specificity of contrast enhanced CTC to detect choledocholithiasis are comparable to those of MRC (sensitivity 86–93% and 80–95%, respectively, and specificity 94–100% and 88–96%, respectively) [3, 8, 18, 19]. CTC is also faster than MRC, which may be of importance in patients with difficulties in lying in the supine position for a prolonged time or when evaluating severely ill patients.
CTC has been used to preoperatively evaluate aberrant bile ducts before laparoscopic cholecystectomy. The frequency of anatomic variants that may affect the outcome of laparoscopic cholecystectomy was estimated to be 15% with CTC [16, 20, 21]. In clinical practise, the frequency of bile duct injuries is about 0.5–1.5% [22, 23]. The potential value of pre-operative mapping of the biliary system by using CTC must therefore be weighed against the cost and radiation.
With injection of contrast media via biliary drainage catheters, CTC has been successfully used to visualize the extent of ductal invasion by hilar carcinoma . Whether administration of contrast media orally or intravenously may achieve similar results in patients without drainage has not been shown.
CTC has been shown to provide kinetic and functional information . This is also possible in contrast enhanced MRC when hepatocyte specific contrast media is used (Gd-BOPTA and Gd-EOB-BOPTA). Further studies are required to evaluate whether contrast enhanced MRC or CTC should be preferred to evaluate biliary kinetics.
The main disadvantages of CTC compared to MRC are the use of radiation and contrast media. In our study, including the literature review, the frequency and severity of adverse reactions was low when infusing the contrast media. The disadvantage of infusion is the need of supervision, which is impractical in a radiology department. In our setting, this problem was solved by admitting the patients to a ward for infusion prior to CTC.
This study indicates that drip infusion CTC with an infusion rate of iotroxate governed by the serum bilirubin concentration is a feasible and safe tool in patients with and without impaired biliary excretion. In addition to those with inconclusive MRC or contraindications, CTC is a diagnostic alternative in patients already admitted to the hospital for whom a reliable diagnosis or mapping of the biliary tree is required within a limited time. In younger patients, non-ionising methods (i.e. MRC or a repeated ultrasound examination) should be preferred.
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