Contrast Material and Gallbladder Kinetics: Implications for Same Day Sonography After Intravenous Pyelography or CT Scanning

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1 Contrast Material and Gallbladder Kinetics: Implications for Same Day Sonography After Intravenous Pyelography or CT Scanning Omar Khan, MD, PhD, Rene Naipaul, RDMS, Rajendra Singh Rampaul, MB, BS, Vinesh Abhang, MBBS, MD, DMRE, DNE, Anthony Archibald, MSc, Paramanand Maharaj, FRCR, Shehenaz Mohammed, MB, BS, Lisa Mohammed, MB, BS Sonographic examination of the gallbladder has allowed us to study the effects of various substances on this organ. A prospective study involving 77 patients was undertaken to evaluate the effects of intravenous or oral contrast agents on gallbladder volume changes in patients without known gallbladder disease. A mean volume after contraction of 24.8% was observed after administration of intravenous contrast agent (P < 0.01) and of 31.9% after oral administration (P < 0.01). This phenomenon of contraction of the gallbladder should therefore be recognized when sonographic or computed tomographic evaluation of the gallbladder is undertaken after imaging procedures that use radiographic contrast agents either intravenously or orally. KEY WORDS: Contrast agent; Intravenous pyelography, Gallbladder; Urography, intravenous. Patients investigated for right hypochrondrial pain at our institution are frequently scheduled for IVU and simultaneous same day abdominal ultrasonography to exclude pathologic conditions of the gallbladder if the IVU is normal. A similar request for a CT scan of the abdomen often ABBREVIATIONS IVU, Intravenous urography; CT, Computed tomography; AP, Anteroposterior; TS, Transverse section; LS, Longitudinal section; CCK, Cholecystokinin Received January 18, 1999, from the Department of Radiology and Nuclear Medicine, University of the West Indies, St. Augustine, Trinidad, West Indies. Revised manuscript accepted for publication July 24, Address correspondence and reprint requests to Omar Khan, MD, PhD, Department of Radiology and Nuclear Medicine, EWMSCA, Champs Fleurs, Trinidad, West Indies. pertains if the IVU is normal. This clinical strategy has cost-saving implications for hospitalization and often permits expeditious patient management. However, adequate sonographic assessment of the gallbladder requires that this viscus be distended as fully as possible. Usually this is accomplished by an overnight fast. If it were to be demonstrated, however, that changes in volume of the gallbladder occurred, and particularly if significant contraction takes place after intravenous or oral administration of contrast media, this could result in a serious flaw in the same day strategy of combined IVU, sonogram, or abdominal CT of the gallbladder. Contrast agents are iodinated compounds with properties that permit the visualization of structures not normally seen on plain radiographs. 1 They can be divided into conventional (ionic) and low osmolar (nonionic). Both groups are used, although the former is gradually being replaced for intravenous administration because of known important adverse 1999 by the American Institute of Ultrasound in Medicine J Ultrasound Med 18: , /99/$3.50

764 CONTRAST MATERIAL AND GALLBLADDER J Ultrasound Med 18:763 767, 1999 reactions resulting from the high blood osmolarity changes.

Their effects on various physiologic parameters in a number of organ systems have been described, including at least one report in the literature on the effects of oral contrast agents on the

2 764 CONTRAST MATERIAL AND GALLBLADDER J Ultrasound Med 18: , 1999 reactions resulting from the high blood osmolarity changes. 2 The conventional agents are more economical and are still widely used as oral contrast agents for CT studies of the abdomen. Their effects on various physiologic parameters in a number of organ systems have been described, including at least one report in the literature on the effects of oral contrast agents on the gallbladder. 3 To our knowledge, gallbladder volume changes after administration of intravenous contrast material (low osmolar and conventional) have not been previously investigated, nor have any comparative studies been performed to evaluate the effects of both oral and intravenous contrast agents on this organ. We used sonography to investigate the changes in gallbladder volume on the clinically undiseased gallbladder after giving contrast agents via the intravenous and oral routes of administration. The clinical implications of this study are that it can assist in establishing a preferred sequence of radiologic investigations of the gallbladder on the same day in cases in which a sonogram is requested simultaneously after obtaining a normal IVU or contrast-enhanced CT scan of the abdomen. This approach would help to ensure that gallbladder volume is least affected and thus maximize the interpretive value of sonography. MATERIALS AND METHODS Figure 1 Ultrasonogram of gallbladder shows pre contrast administration state (fasting). (LS and TS.) Each preparation contained 300 mg iodine per milliliter. Two types of intravenous contrast agents were used in this study. Two were low osmolar, nonionic (iohexol [Omnipaque], iopromide [Ultravist]), and two were conventional or standard (meglumine diatrizoate [Urografin] and meglumine and sodium amidotriazoate [Hypaque]). Urografin was used as the agent for oral administration at 6 ml and 12 ml, mixed with water to volumes of 250 and 500 ml, respectively. Seventy-seven patients were prospectively selected for entry into this study. These were patients referred for excretory urography or abdominal CT. They were all without known gallbladder disease and were excluded if they had any concurrent acute illness, intraabdominal sepsis, or gastrointestinal malignancy. All subjects were fasting. Figures 1 and 2 show the gallbladder before and after administration of contrast agent, respectively. Group A consisted of 51 patients (32 male, 19 female; age range, 25 to 52 years) who received intravenous contrast material. Fifteen received low osmolar contrast agent and 36 received standard intravenous contrast material. The volume of injected contrast material was 1.4 ml/kg. Ten patients (five male, five female; age range, 20 to 45 years) who received 1.4 ml/kg physiologic saline solution intravenously at room temperature acted as controls. Group B (26 patients, 12 male and 14 female; age range, 16 to 67 years) received either 250 or 500 ml of oral contrast material with a concentration of 300 mg iodine per milliliter. Twenty patients (11 male, 9 female; age range, 18 to 42 years) who received 250 ml of water orally acted as controls for this group. Ten patients (five male, five female; age range, 18 to 38 years) who had CT of the abdomen without contrast enhancement also were used as controls for this group. Figure 2 Scan demonstrates contraction of the gallbladder after intravenous administration of contrast medium. (LS and TS.)

3 J Ultrasound Med 18: , 1999 KHAN ET AL 765 All patients underwent ultrasonography of the gallbladder before and between 10 and 15 min (mean, 12 min) after administration of the contrast agent. Gallbladder volume was measured sonographically using a 3.5 MHz curvilinear phased array probe (Acoustic Imaging, Phoenix, AZ). The mean of two measurements was used to calculate the volume using a prolate ellipsoid formula (AP TS LS ) (Figs. 1, 2). A scanning time of between 10 and 15 min was chosen to assess gallbladder volume as the determination of obstructive uropathy from an IVU series is readily apparent in most instances from films obtained within this period. All patients in both groups were scanned by the same sonographer (R.N.) who was unaware whether the patient had received the contrast agent orally or intravenously. The percentage change in gallbladder volume before and after administration of contrast material was analyzed for statistical significance using the null hypothesis. RESULTS In group A, 39 patients demonstrated contraction of the gallbladder, with a mean contraction of 24.8% (range, 1 to 45.7%) (Fig. 3). This contraction was significant compared to the noncontrast values (P < 0.01). However, no statistical significance was found between the responses to low osmolar and conventional contrast media. The controls for group A patients showed no significant change in gallbladder volume at 10 to 15 min. In those who received contrast agent orally (group B), a significant contraction occurred in both subgroups (i.e., 250 ml and 500 ml) compared to volumes in those who did not receive contrast agent, with a mean contraction in volume of 31.9% (P < 0.01) (Fig. 4). The differences in volumes of ingested contrast material showed no statistically significant difference in the change of gallbladder volume (P < 0.01). The control group for group B patients showed no statistically significant change in gallbladder volume at 10 to 15 min. Interestingly, in 12 patients in group A, expansion of the gallbladder occurred (range, 4 to 12%) (Fig. 5). This effect was observed predominantly with the use of conventional contrast media (eight patients). The data from these patients were included in calculating the overall change in volume after intravenous administration of contrast agent. DISCUSSION It is well understood that the optimal sonographic evaluation of the gallbladder requires adequate distensibility of this viscus, usually accomplished after an established overnight fast. It has not been recognized, however, that gallbladder may change in volume when iodinated contrast materials are injected intravenously, as in the IVU examination, or ingested orally for abdominal CT scanning. This may have implications when sonographic and CT assessments of the gallbladder are performed on the same day. Our findings indicate that although a variable volume change occurs 10 to 15 min after intravenous or oral administration of iodinated contrast material, the dominant response observed was contraction. We infer from these findings that pathologic lesions of the gallbladder could be missed in these situa- Figure 3 Graph shows percentage change in gallbladder volume when contrast agent is given intravenously (group A). Figure 4 Graph shows percentage change in gallbladder volume when contrast agent is given orally (group B).

766 CONTRAST MATERIAL AND GALLBLADDER J Ultrasound Med 18:763 767, 1999 Figure 5 Graphs shows number of patients with either contraction or expansion of the gallbladder after administration of

4 766 CONTRAST MATERIAL AND GALLBLADDER J Ultrasound Med 18: , 1999 Figure 5 Graphs shows number of patients with either contraction or expansion of the gallbladder after administration of various types of contrast agent intravenously (group A). tions; however, no proof of this can be offered because of the population group we studied. It may be interesting to repeat this study in patients with established pathologic conditions of the gallbladder to ascertain what entities go undetected, if any. Indeed, in our series the range in volume reduction encountered did not result in nonvisualization of the gallbladder in any of the patients in either group. It would appear, however, that the dominant response, namely contraction, may be attributable to a property of the contrast material itself, as neither the ingestion of water nor the administration of intravenous saline solution or obtaining of plain non contrast-enhanced CT scans had any significant effect on gallbladder contraction. It is possible that gallbladder volume is sensitive to osmolarity changes, although we found no statistical difference in gallbladder contraction between low osmolar and conventional contrast material when either was administered intravenously. In the case of orally administered contrast agents, it is difficult to postulate volume changes on the basis of osmolarity. It is recognized that in addition to causing gallbladder contraction, CCK induces relaxation of the sphincter of Oddi, which facilitates the antegrade flow of bile it receives during gallbladder contraction. The sphincter of Oddi tone increases during fasting, but meal ingestion paradoxically inhibits gastric emptying by contraction of the pyloric sphincter. 4 The presence of gastric content of any type may thus indirectly influence CCK secretion. It is clear that the mechanisms of gallbladder contraction are complex and are related to a wide variety of substances that evoke cholecystokinin release. 5 7 Such substances include fatty acids within the duodenum, but other acid products of digestion and calcium salts also have been reported to cause the release of CCK. Unknown to us, one of the contrast agents, Hypaque, contained edetate calcium disodium, 1:10,000, as a stabilizer, but the effect of such a small quantity of calcium on gallbladder contraction is of dubious significance. The degree of gallbladder emptying is CCK dose dependent. Whereas the ejection fraction of the gallbladder is known to increase as the dose of CCK is enhanced, a decrease is observed when larger doses are used. The paradoxical response in normal subjects is believed to be due to different threshold level of CCK receptors within the body, fundus, and cystic duct, and these themselves may demonstrate individual variations. 8 The variable responses in our study may be related to effects, direct or indirect, on these receptors and to individual variation in the total number of receptors in gallbladder wall smooth muscle. 9 We conclude from this study that the use of both intravenous and oral contrast agents results in gallbladder contraction 10 to 15 min after administration, but it is doubtful whether this could lead to serious misdiagnosis of pathologic lesions of the gallbladder. Nevertheless, this factor should be borne in mind after the use of contrast agents, and the sonographic study should be repeated if the results are equivocal. We are currently investigating at what point gallbladder volumes return to pre-contrast values. This could be of importance if it is imperative to complete all radiologic investigations within 24 h. REFERENCES 1. Thomas SM, Williams J, Adam EJ: Intravascular contrast media. Clin Radiol 52:59, Grainger RG: Osmolarity of intravenous radiological contrast media. Br J Radiol 53:739, Starinski R, Alon A: Gallbladder size: Is it affected by the oral intake of water or dilute contrast medium? J Ultrasound Med 13:435, Krishnamurthy S, Krishnamurthy G: Biliary dyskinesia: Role of the sphincter of Oddi, gallbladder, and cholecystokinin. J Nucl Med 38:1834, Muraca M, Gianci V, Vilei MT, et al: Ultrasonic evaluation of gallbladder emptying with ceruletide. Ital J Gastroenterol 28:38, Bird NC, Wegstapel H, Chess-Williams R, et al: In vitro contractility of stimulated and non-stimulated human gallbladder muscle. Neurogastroenterol Motil 8:63, Cicala M, Corazziari E, Diacinti D, et al: Effect of endogenous cholecystokinin on post prandial gallbladder refilling. Dig Dis Sci 40:76, 1995

5 J Ultrasound Med 18: , 1999 KHAN ET AL Steigerwalt RW, Goldfine ID, Williams JA: Characterization of cholecystokinin receptors on bovine gallbladder membranes. Am J Physiol 247:G709, Upp JR, Nealon WH, Singh P, et al: Correlation of cholecystokinin receptor with gallbladder contractibility in patients with gallstones. Am Surg 205:641, 1987

Usefulness of Fatty-meal Stimulated Gallbladder Contractility by Ultrasonography in the Diagnosis of Acute Cholecystitis

O R I G I N A L A R T I C L E Usefulness of Fatty-meal Stimulated Gallbladder Contractility by Ultrasonography in the Diagnosis of Acute Cholecystitis Yuan-Ming Tsai 1,2 2, Chiao-Hsiung Chuang *, Hsiu-Chi