Published online before print April 18, 2008, 10.1148/radiol.2473070964
(Radiology 2008;247:733-737.)
© RSNA, 2008
CT Cholangiography in Potential Liver Donors: Effect of Premedication with Intravenous Morphine on Biliary Caliber and Visualization1
Richard S. Breiman, MD,
Fergus V. Coakley, MD,
Emily M. Webb, MD,
James J. Ellingson, MD,
John P. Roberts, MD,
Jennifer Kohr, MD,
Juergen Lutz, MD,
Naomi Knoess, MD, and
Benjamin M. Yeh, MD
1 From the Departments of Radiology (R.S.B., F.V.C., E.M.W., J.J.E., J.P.R., J.K., J.L., N.K., B.M.Y.) and Surgery (J.P.R.), University of California San Francisco, 505 Parnassus Ave, Box 0628, San Francisco, CA 94143-0628. Received June 4, 2007; revision requested August 8; revision received October 2; accepted December 10; final version accepted December 11.
Address correspondence to B.M.Y. (e-mail: ben.yeh{at}radiology.ucsf.edu).
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ABSTRACT
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Purpose: To retrospectively determine whether premedication with intravenously administered morphine improves bile duct caliber and visualization in potential liver donors undergoing computed tomographic (CT) cholangiography.
Materials and Methods: This was a retrospective single institution study approved by the institutional review board and compliant with requirements of the HIPAA. Multidetector CT cholangiography was performed after slow infusion of 20 mL of iodipamide meglumine 52% diluted in 80 mL of normal saline in 143 consecutive potential liver donors (81 men and 62 women; mean age, 37 years); 43 received premedication with intravenous morphine sulfate (0.04 mg per kilogram of body weight) and 100 did not. Two independent readers recorded common bile duct diameter and area on axial CT images. Readers also scored bile duct visualization, including all second-order biliary branches, on a four-point scale (0, not seen; 3, excellent visualization).
Results: For scans obtained without and those obtained with morphine, there was no significant difference in the mean common bile duct diameter (4.1 vs 4.3 mm for reader 1 and 4.4 vs 4.6 mm for reader 2, respectively; P > .39 for both readers), in common bile duct area (20.7 vs 21.5 mm2, for reader 1 and 21.3 vs 20.2 mm2 for reader 2, respectively, P > .60 for both), or in second-order bile duct visualization score (2.34 vs 2.36 for reader 1 and 2.58 vs 2.50 for reader 2, respectively; P > .5 for both).
Conclusion: The results suggest that premedication with intravenous morphine prior to CT cholangiography in potential liver donors does not increase bile duct caliber or improve biliary visualization.
© RSNA, 2008
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INTRODUCTION
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Living-related liver donation is increasingly performed because of the nationwide shortage of cadaveric livers available for transplantation. The preoperative evaluation of biliary tract anatomy is important for the evaluation of potential liver donors because variant anatomy, particularly of the second-order ducts, is seen in up to 45% of the population and can affect the surgical approach and biliary anastomotic technique (1,2). The presurgical evaluation of second-order bile duct anatomy is challenging because of the small diameter of normal-caliber bile ducts. Several publications have suggested that computed tomographic (CT) cholangiography (CT performed after intravenous administration of a biliary contrast medium) is a safe technique for the noninvasive evaluation of biliary anatomy (3,4) and that it may be more accurate than magnetic resonance (MR) cholangiography for patients with nondilated bile ducts (5).
Premedication with intravenously administered morphine has been reported with CT cholangiography (5) because morphine is known to contract the sphincter of Oddi and may potentially promote biliary distension and improve biliary visualization (6–8), and because morphine has been successfully used to augment radionuclide cholescintigraphy (9–13). However, no studies have reported the effect of morphine on biliary caliber or visualization during CT cholangiography. Therefore, we undertook this study to retrospectively determine whether premedication with intravenous morphine improves bile duct caliber and visualization in potential liver donors undergoing CT cholangiography.
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MATERIALS AND METHODS
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Patients
This was a retrospective study approved by our institutional Committee on Human Research and was compliant with requirements of the Health Insurance Portability and Accountability Act. Patient consent for our retrospective study was waived by the committee. We identified all patients (n = 143) who were evaluated for possible liver donation from October 2001 to March 2005 and underwent CT cholangiography. There were no exclusion criteria. The patients consisted of 81 men and 62 women, with a mean age of 37 years (range, 18–56 years). The mean age of patients who received morphine and patients who did not was similar (37.1 and 36.8 years, respectively; P = .87 with unpaired Student t test), and the sex ratio of patients who received morphine and patients who did not was similar (29 men and 14 women compared with 52 men and 48 women, respectively; P = .09 with 
2 test).
CT Cholangiography Technique
The first 43 patients had been premedicated with an intravenous bolus of morphine sulfate (Abbott Laboratories, Chicago, Ill) (0.04 mg per kilogram of body weight) just prior to the start of intravenous administration of cholangiographic contrast material. Because our initial results showed CT cholangiography was reliable and accurate and a prior study showed excellent CT cholangiography results in living potential liver donors without morphine premedication (14), we decided to omit this component of the premedication regime, and the latter 100 patients did not receive intravenous morphine. Because of older studies (15–17) suggesting biliary contrast media commonly cause hypersensitivity reactions, all patients were also premedicated with 25 mg of intravenous diphenhydramine (Benadryl; Pfizer, New York, NY) and then given a 30-minute infusion of 20 mL of iodipamide meglumine 52% (Cholografin; Bracco Diagnostics, Princeton, NJ) diluted in 80 mL of normal saline.
For all patients, the liver was imaged 15 minutes after completion of iodipamide meglumine infusion by using a single breath-hold 1.25- or 2.5-mm collimation multi–detector row CT scanner (LightSpeed; GE Medical Systems, Milwaukee, Wis). Patients imaged prior to February 2002 (n = 8) were examined by using a four–detector row scanner with a section thickness of 2.5 mm; all subsequent patients (n = 135) were examined by using a 16–detector row scanner with a section thickness of 1.25 mm. All patients were observed for contrast material reactions. Images were reconstructed at 0.625–1.25-mm intervals with a reduced field of view targeted to the liver. These targeted datasets were postprocessed on a threedimensional workstation (Advantage Windows 4.0; GE Medical Systems) by a specially-trained radiology technologist using oblique coronal and axial maximum intensity projections and volume-rendered three-dimensional reformations. All patients had undergone CT angiography with arterial and venous phase imaging of the liver on the same day within 2 hours prior to CT cholangiography.
Image Interpretation
Two subspecialty-trained abdominal radiologists (E.M.W., J.J.E.), each with 1-year specialty experience with abdominal CT and neither of whom had been involved with the initial interpretation of the CT cholangiograms, independently reviewed all images (ie, axial and three-dimensional images) of the 143 patients by using a picture archiving and communication system workstation (Impax; Agfa, Mortsel, Belgium). Readers were aware that patients were potential liver donors but were unaware of all other clinical and imaging information, including whether morphine premedication had been administered. In particular, readers were unaware whether patients had or had not received premedication with intravenous morphine.
Readers recorded the following parameters: (a) maximum short-axis diameter of the common bile duct in the head of the pancreas as seen on axial CT images; (b) maximum cross-sectional area of the common duct in the head of the pancreas as seen on axial CT images, measured with an elliptical region of interest tool; and (c) bile duct visualization score by using a previously described method (4). Each of the 12 biliary tract segments was scored on a scale of 0 to 3. The biliary tract segments consist of the common duct (one segment), cystic duct (one segment), first-order right and left main ducts (two segments), second-order branch ducts (four segments), and third-order branch ducts (four segments). Common, cystic, first-order branch, and second-order branch ducts were scored as follows: 0, not visualized; 1, faintly seen; 2, identified but the origin or portions of the duct are not visualized; and 3, excellent visualization from origin to branches. Third-order branch ducts were scored for each segment as follows: 0, not visualized; 1, third-order branches faintly seen; 2, one or two third-order branches clearly seen; and 3, excellent visualization of third-order branches.
Statistical Analysis
Statistical analyses were performed by using Stata software package, version 8.0 (Stata, College Station, Tex). For each reader, the visualization scores for the bile duct branches (first-, second-, and third-order) were compared between CT cholangiograms obtained with morphine premedication or those obtained without by using generalized estimating equations with a random-effects model and accounting for the presence of multiple bile duct branch scores within the same patient, patient sex, patient age, and CT section thickness. A P value of less than .05 was considered to indicate a statistically significant difference.
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RESULTS
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No significant difference in common bile duct caliber at CT cholangiography was found between patients who received premedication with intravenous morphine and those who did not (Figs 1–3; Table 1). Similarly, no statistically significant difference in biliary visualization scores was seen between the patients who received premedication with intravenous morphine and patients who did not (Table 2). There was no significant interobserver difference between the two readers in the assessment of bile duct visualization or bile duct size, from the largest common bile duct to the smallest third-order bile duct branches, including the clinically important and often challenging second-order ducts.
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Figure 1: Axial CT cholangiogram obtained with intravenous morphine premedication and postbiliary contrast material shows common bile duct (arrow) where the duct area and diameter were measured at the level of the head of the pancreas.
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Figure 2: Coronal maximum intensity projection CT cholangiogram without morphine premedication demonstrates normal-caliber bile ducts, including anomalous drainage of posterior segmental (second-order) bile duct (arrow) into the left bile duct. Third-order bile ducts (arrowheads) show excellent visualization (score of 3).
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Figure 3: Coronal maximum intensity projection CT cholangiogram with preprocedure morphine administration. The right anterior third-order bile ducts (arrowhead) are partially visualized (score of 2). Arrow = duodenum.
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Table 1. Effect of Premedication with Morphine on Common Bile Duct Caliber at CT Cholangiography in Potential Liver Donors
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Table 2. Effect of Premedication with Morphine on Biliary Visualization at CT Cholangiography in Potential Liver Donors
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Two minor contrast material reactions were noted, consisting of one case each of mild self-limiting urticaria and wheezing. Neither of these reactions required treatment.
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DISCUSSION
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Our negative results suggest that premedication with intravenous morphine neither improves bile duct distension nor visualization at CT cholangiography. This finding is important because it indicates CT cholangiography can be performed without the logistical hurdles connected with the use of a class 1 drug, which requires aftercare and postprocedural restrictions that are associated with intravenous administration of a sedating agent, and without the potential side effects of intravenous morphine. Since living donors are increasingly evaluated at preoperative imaging and since CT cholangiography is increasingly requested in this population, any simplification of the imaging protocol is a welcome advance. The logical next step would be to investigate whether premedication with intravenous diphenhydramine is worthwhile, since this is also a sedating drug that is routinely administered to patients about to undergo CT cholangiography.
Our study findings appear to conflict with the established benefit of morphine to improve the results of cholescintigraphy (9–13). The basis of this discrepancy is unclear. It is possible that radiographic biliary contrast medium itself causes biliary distension and that morphine has no incremental effect in this setting; however, this is speculative. Our study findings also contradict a review stating that premedication with morphine improved biliary visualization during MR cholangiography (18); however, in that review no data were included to support the statement. It is possible that the apparent improved definition of normal caliber bile ducts at MR cholangiography described in that review could have been secondary to reduced patient motion related to preprocedural morphine rather than a direct effect on the bile ducts.
Our study had a number of limitations. First, patients were not randomly assigned to receive or not receive morphine. However, all patients were healthy and it is difficult to imagine how any selection bias might have been generated with our methods. Second, the scientifically ideal study would have been to perform CT cholangiography on two different occasions in the same group of patients, once with morphine and once without. However, this would have been difficult to justify ethically, as potential liver donors would have been subjected to additional radiation and the potential risk of an adverse reaction to a second administration of a biliary contrast material.
Another limitation is that we did not vary our method of morphine administration. We administered morphine as a single intravenous bolus just prior to the time of initiation of biliary contrast material infusion (45 minutes prior to imaging) and did not examine other modes of morphine administration, such as slow infusion, divided doses, or delayed-release subcutaneous or intramuscular preparations. Of note, a single intravenous dose appears to be the most common method of morphine delivery for cholescintigraphy (9–13). In addition, we did not vary the timing of morphine administration relative to the administration of biliary contrast material.
An additional limitation is that the first eight of 43 patients who received morphine premedication were scanned on an older generation CT scanner using thicker sections. Though these patients are few, they may have contributed to a slightly poorer visualization of bile ducts than might have been achieved in those patients. Nevertheless, the number of these patients is low and therefore unlikely to contribute substantially to the results.
In conclusion, our results suggest that premedication with intravenous morphine prior to CT cholangiography in potential liver donors does not improve bile duct caliber or visualization, including the clinically relevant second-order ducts.
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ADVANCE IN KNOWLEDGE
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- Premedication with intravenous morphine prior to CT cholangiography in potential liver donors does not increase bile duct caliber or improve visualization, including the clinically relevant second-order ducts.
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IMPLICATION FOR PATIENT CARE
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- Premedication with intravenous morphine does not improve the CT cholangiographic evaluation of potential liver donors.
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FOOTNOTES
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Author contributions: Guarantor of integrity of entire study, B.M.Y.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, R.S.B., B.M.Y.; clinical studies, R.S.B., F.V.C., E.M.W., J.J.E., J.P.R., B.M.Y.; statistical analysis, B.M.Y.; and manuscript editing, R.S.B., F.V.C., B.M.Y.
Authors stated no financial relationship to disclose.
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ABSTRACT
INTRODUCTION
