ORIGINAL ARTICLE 
Annals of Nuclear Medicine Vol. 9, No. 4, 225-228, 1995 
Morphine-augmented cholescintigraphy enhances duodenogastric reflux 
Wei-Jen SHIH,* Jong-Kang LEE,** Sylvia MAGoUN,* Becky WIERZBINSKl* and U Yun RYo* 
*Nuclear Medicine Service, Veterans Affairs Medical Center, Division of Nuclear Medicine. Department of Diagnostic Radiology, University of Kentucky Medical Center, USA **Department of Nuclear Medicine, China Medical College Taichung, Taiwan, Republic of China 
Morphine intervention in cholescintigraphy decreases imaging time to diagnose acute cholecystitis. Not infrequently we observe duodenogastric reflux during scintigraphy with and without morphine intervention. To evaluate occurrence of duodenogastric reflux related to morphine, we reviewed 55 patients who underwent cholescintigraphy with (32) and without (23) morphine intervention. Morphine was injected when there was bowel activity with non-visualization of the gallbladder at 60 min. Duodenogastric reflux was identified by the appearance of activity in the area just below or immediately adjacent to the ti p of the left hepatic lobe laterally. Among 32 patients with morphine intervention, 19 had acute cholecystitis and 1 3 chronic cholecystitis. Eleven of 1 9 (58%) with acute cholecystitis had duodenogastric reflux and 6 of 13 (46%) had duodenogastric reflux in chronic cholecystitis. The total of duodenogastric reflux in the group with morphine injection was 53% . Two patients' duodenogastric reflux occurred before morphine injection and was more apparent after morphine was given. In the without morphine group, 3 had acute cholecystitis and 20 had chronic cholecystitis; 2 (one acute and one chronic cholecystitis) of these 23 (9%) had duodenogastric reflux. Our results indicate: (1) occurrence of DG reflux in morphine augmented cholescintigraphy is not significantly different in cholecystitis from that in chronic cholecystitis; (2) duodenogastric reflux in morphine augmentation occurs significantly more often than without morphine interven-tion (p < 0.001). We conclude that cholescintigraphy with morphine enhances duodenogastric reflux. The degree of duodenogastric reflux in the acute cholecystitis patients has been more severe than in the chronic cholecystitis patlents. 
Key words: cholescintigraphy, duodenogastric reflux, morphine, acute cholecystitis, chronic cholecystitis, Tc-99m BRIDA, sphincter of Oddi 
 INTRODUCTION 
NONVISUALIZATION of the gallbladder in hepatobiliary scintigraphy is a hallmark of acute cholecystitis. Presumably cystic duct obstruction is almost always associated with acute cholecystitis and non-visualization of the gallblad-der reflects obstruction of the cystic duct. Morphine inter-vention in cholescintigraphy decreases imaging time to diagnose acute cholecystitis. I With intravenous injection of a smaller dose of morphine sulfate contraction of the sphincter of Oddi results in increased intraluminal pres-sure in the common bile duct, and promotes bile flow through a patent cystic duct. I Not infrequently we observe duodenogastric reflux during hepatobiliary imaging after the morphine injection. Oates and Achong2 studied I 14 patients with morphine-augmented cholescinti graphy and concluded that a majority of patients with acute and chronic cholecystitis experienced gastric reflux.2 We stud-ied the patients undergoing cholescintigraphy with and without morphine intervention to assess morphine-re-lated duodenogastric reflux. 
MATERIALS AND METHODS 
Fifty-five patients' cholescintigraphies were reviewed, and these cholescintigraphies were referred for suspected acute cholecystitis. Cholescintigraphy was performed after intravenous injection of 5-8 mCi ( 185-296 MBq) of Tc-99m mebrofenin in those patients who had been fastlng for at least 4 hours. Sequential 2-, 5-, lO-, 15-, 30-, 45-, and 60 min images were obtained. Morphine sulfate, 0.04 mg/kg usually 2-3 mg, was IV injected when the patient exhiblted bowel activity without gallbladder activity usually 45-50 min after radiopharmaceutical administration. Duodenogastric reflux was Identified by radioactivity appearance in the area just below or immedlately adjacent to the tip of the left hepatic lobe laterally.3 In those patients without morphine intervention, imaging was performed every 30 min after routine 60 min study up to 4 hrs. Clinical, surgical and/or pathological findings were correlated with scintigraphic results. 
RESULTS 
These patients' cholescintigraphies were divided into two categories: cholescintigraphy with morphine intervention (32 patients); and cholescintigraphy without morphine intervention (23 patients). Among the 32 patients with morphine intervention, 19 had non-visualization of the gallbladder (acute cholecystitis), 1 3 with gallbladder vi-sualization (chronic cholecystitis). All 19 patients with acute cholecystitis underwent cholecystectomy whlch 
proved to be acute inflammation by histopathology . Eleven of the 19 (58%) patients with acute cholecystitis had duodenogastric reflux, while 6 of 13 (46%) patients with chronic cholecystitis demonstrated duodenogastric reflux. Thc amount o_ f duodenogastric reflux (Fig. 1 ) of the patients with nonvisualization of the gallbladder (acute cholecystitis) is consistently higher than that of the patients with visualization of the gallbladder (chronic cholecystitis) (Fig. 2). The amount of duodenogastric reflux has been estimated by the extent of the area of radioactivity in the gastric region and intensity of the radioactivity. 
Of the group receiving a morphine injection, 53% exhibited D-G reflux. Two patients' duodenogastric re-flux which occurred before morphine injection became apparent after morphine was given (Fig. 3). 
Among 2-3 patients without morphine intervention, three patients had acute cholecystitis and 20 had delayed visualization of the gallbladder (chronic cholecystitis); two (one acute and one chronic cholecystitis) of these 23 (9%) had duodenogastric reflux. 
Occurrence of duodenogastric refiux in morphine-aug-mented cholescintigraphy is not a statistically significant difference between acute and chronic cholecystitis (p = 0.5l); duodenogastric reflux after morphine augmentation occurred at a significantly higher rate than without morphine intervention (p < 0.001 ).
DISCUSSION 
Norma] Tc-99m IDA cholescintigraphy will be obtained if there is integrity of hepatocyte uptake, patent intrahepatic ducts, cystic duct, and common bile duct, normnal gall-bladder function, and normnal function of the sphincter of Oddi . Appearance of radioactivity occurs in the following order: cardiac blood pool, the liver, intrahepatic ducts, gallbladder, and bowel . Cholesci ntigraphy has been proven a highly efficacious approach to the diagnosis of acute and chronic cholecystitis. Nonvisualization of the gallbladder reflecting cystic duct obstruction is a hallmark of acute cholecystitis .4 Cholescintigraphy also enables noninvaslve identification of duodenogastric refl ux.2,3.5~7 Various etio-logical factors result in duodenogastric reflux or entero-gastric reflux ; these include exploratory laparotomy, acute and chronlc cholecystitis,2.3.5,x-13 peptic ulcer disease, and chronic gastritis.6.7 Our previous study3 concluded that gallbladder dysfunction or nonfunction is demonstrated more frequently when duodenogastric reflux Is present than with normal gallbladder function.3 
Opioid drugs have several pharrnacological effects on the upper gastrointestinal tract. For example, morphine sulfate contracts the sphincter of Oddi and pylorus and also increases the resting tone of the stomach, duodenum, and small intestine, causing periodic, nonpropulsive spas-modic contracts in the proximal small bowel, and delayed gastric emptying. [4 Morphine causes constriction of Oddi with the common bile duct pressure increasing more than lO fold.14 The pressure in the bile duct facilitates flow of the intravenous Injection of Tc-99m IDA into the gall-bladder through the cystic duct durlng cholescintigraphy . If the gallbladder is not visualized In 45 min when there is bowel activity, typically 0.04 mg/kg1 or usually 2 mg of IV morphine is admlnistered. Imaging is then continued for another 30 mins; thus morphine intervention has been shown to reduce imaging time from 4-24 hrs to about 90 mins.1'15 
Our results indicate that the morphine intervention group had enhanced duodenogastric reflux as compared to patients who did not receive morphine intervention in two ways: either by an increase in reflux volume or by the presence of reflux from the absence of reflux. These find-ings were paradoxical in relation to the pharrnacological actions of morphine. This paradoxical finding, entero-gastric reflux after morphine injection, has also been described as occurring in 86% of acute cholecystitis cases and in 80% of chronic cholecystitis cases.2 Enterogastric reflux increased after morphine given to 57%2 and 2 of the patients with reflux had increased reflux. Our findings show that the degree of duodenogastric reflux in acute cholecystitis patients was more severe than that of chronic cholecystitis and has not been previously described. The mechanism of this paradoxical finding is unknown. Oates et al. hypothesized as follows: morphine Induced intestinal spasms and preexisting duodenal Inflammation sec-ondary to adjacent cholecystitis may result in synergically exaggerated retrograde peristalsis. This mechanism re-quires further investigation. 
In summary, duodenogastrlc reflux or enterogastric reflux on cholescintigraphy has been enhanced by mor-phine administration. Constriction of the sphincter of Oddi, as an effect of morphine adminlstration, causes radiopharmaceutical already present in the small bowel to be redistributed to the stomach through the pyloric sphinc-ter. Reflux occurred more significantly with morphine intervention than without it; the degree of duodenogastric reflux was more severe in the acute cholecystitis patients than in the chronic cholecystltis patients. Thus duodeno-gastric or enterogastric reflux on cholesclntigraphy was enhanced by morphine administration. 
ACKNOWLEDGMENT 
We express our appreciation to Ms. Lillian Owens and Mrs. Aleene Miller for their secretarial help during the preparation of the manuscript. 
REFERENCES 
1. Choy D, Shi EC, McLean RG, et al. Cholescintigraphy in acute cholecystitis: use of intravenous morphine. Radiol-ogy 151: 203 1984. 
2. Oates E Achong DM. Incidence and significance of enterogastric reflux during morphine augmented chole-scintigraphy. Clin Nucl Med 17: 926-928, 1992. 
3. Shih WJ, Coupal JJ, Domstad PA, et al. Disorders of gallbladder function related to duodeno-gastric reflux in technetium-99m DISIDA hepatobiliary scintigraphy. Clin Nucl Med 12: 857, 1987. 
4. Freitas JE. cholec stitis. Cholescintigraphy in acute and chronic Semin Nucl Med 12: 18, 1982. 
5. Shih WJ, Fockele DS. Enterogastric reflux dernonstrated by radionuclide hepatobiliary scintigraphy. Semin Nucl Med 20: 367, 1990. 
6. Wang GX, Shih WJ, Tang PL, et al. Duodenogastric reflux dernonstrated by cholescintigraphy in peptic ulcer disease and chronic gastritis. Clin Nucl Med 19: 100-l03, 1994. 
7. MackieCR, Wisbey ML.Caschieri A. MilkTc-99m EHIDA test for enterogastric: bile reflux. Br J Surgery 69: I Ol -1 04, 1982. 
8. Mack MJ, Slavin JD, SpencerRD, et al. Two false negative results using morphine sulfate in hepatobi li ar y sci ntigraphy. Clin Nucl Med 14: 87-88, 1989. 
9. Tolin RD, Malmud LS, Stelzer F, et al. Enterogastric refiux in normal subjects and patients with Billrowth 11 gastro-
enterostom . Gastroenterology 77: l027 , 1979. 
10. Drane WE, Hanner JS. Complete duodenogastric reflux: A sign of significant duodenal pathology, J Nucl Med 301 : 1568-1570 1990. 
l1. Dufresne F, CarrierL. Gagnon M, et al. Scintigraphic study of duodenal-gastric reflux in cases of primary gastropathy, chronic ulcer of the duodenal bulb, and Moynihan's dis-ease. J Nucl Med 29: 17-22, 1989. 
12. Boureakas EC. Tupler RH, Turbiner EH. Morphine-aug-mented cholescintigraphy with a false-negative result and an apparent ectopic gallbladder. Clin Nucl Med 17: 93 1 -932, 1992. 
13. Yeo EE, Low JC, Azizi F. False-negative morphine-aug-mented cholescintigraphy in a patient with gangrenous cholec stitis. Clin Nucl Med 17: 929-930, 1992. 
14. Jaffe JH, Martin WR. Opioid analgesics and antagonists. In The pharmacological basis of therapeutics, Gilman AG, Rall TW, Nies AS, Taylor P (eds.), 8th ed., Elmsford, NY, Per amon Press, . 485-521, 1990. 
15. Kim EE, Pjura G, Lowry P, et al. Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis. AJR 147: I 177, 1986.