Change in Bile Duct Pressure Responses After Cholecystectomy: Loss of Gallbladder as a Pressure Reservoir

Transcription

1 GASTROENTEROLOGY 1984;87; Change in Bile Duct Pressure Responses After Cholecystectomy: Loss of Gallbladder as a Pressure Reservoir MASAO TANAKA, SEIYO IKEDA, and FUMIO NAKAYAMA Department of Surgery I. Kyushu University Faculty of Medicine. Fukuoka. Japan Coordination of gallbladder and sphincter of Oddi and effect of cholecystectomy on biliary pressure physiology were investigated in 7 patients using an indwelling microtransducer catheter placed in the bile duct by duodenoscopy. Intramuscular morphine (0.2 mg/kg) to induce a sphincter of Oddi spasm produced no change before cholecystectomy but intravenous caerulein (0.1 JLg/kg) induced pressure elevation coincident with gallbladder contraction on echogram. After cholecystectomy, however, morphine caused a pressure rise and a coarse and irregular change of the tracings, which seemed attributable to sphincter of Oddi spasm. Caerulein promptly reduced the pressure and eliminated the irregularity. These results show (a) the sphincter of Oddi relaxes when the gallbladder contracts in response to caerulein and (b) the gallbladder acts as a pressure reservoir against the sphincter of Oddi spasm caused by morphine. The latter implies that the spasm of the sphincter of Oddi readily leads to a pressure rise if the gallbladder is absent, which may partly explain a development of postcholecystectomy syndrome. Functional correlation of gallbladder and sphincter of Oddi (SO) has long been postulated. Yet, its pathophysiologic significance is not completely understood. In the filling phase of the gallbladder, the SO closes while the muscular tone of the gallbladder decreases, resulting in influx of bile into the gallbladder due to a positive pressure gradient from the bile duct to the gallbladder. Conversely, in its emptying phase the SO loosens to permit an outflow of bile Received October 11, Accepted June 9, Address requests for reprints to: Masao Tanaka, M.D., Department of Surgery I, Kyushu University Faculty of Medicine. Fukuoka 812. Japan. The authors thank Dr. H. Tagami and Dr. A. Mihara for providing facilities in Ashiya Central Hospital and Miss S. Kohda for valuable assistance by the American Gastroenterological Association /84/$3.00 from the bile duct into the duodenum. A question often raised is whether removal of the gallbladder causes an unfavorable change in biliary physiology, giving rise to postcholecystectomy symptoms in some cases. Recent advances in endoscopic manometry allow direct nonoperative measurement of bile duct pressure in humans. The present study addresses (a) the presence of coordination between the gallbladder and the SO and (b) the effect of absence of the gallbladder after cholecystectomy on the pressure profile of the bile duct with a hope of explaining possible mechanisms underlying the development of postcholecystectomy syndrome, using an endoscopic manometric method with a microtransducer catheter. Materials and Methods Seven patients (1 man, 5 women) with a mean age of 53 yr, range yr, undergoing cholecystectomy for stones in the gallbladder were selected for the study. An absence of common bile duct stones or any other pathologies in the pancreas and biliary tract was demonstrated by endoscopic retrograde cholangiopancreatography (ERCP) in all patients. Good gallbladder functioning was documented by intravenous cholangiography with egg yolk ingestion. Bile duct pressure measurement was performed before and 2-3 wk after cholecystectomy. The preoperative study was deferred at least 1 wk after the diagnostic ERCP to avoid possible effects of previous cannulation on the SO function. Simultaneous measurement of bile duct pressure and duodenal pressure was carried out in 2 additional patients, a 50-yr-old woman and a 53-yr-old man, who had undergone endoscopic sphincterotomy for the treatment of recurrent or residual stones in the common bile duct to study the correlation between the bile duct and duodenal pressures. Abbreviations used in this paper: ERCP, endoscopic retrograde cholangiopancreatography; SO, sphincter of Oddi.

2 November 1984 GALLBLADDER AS PRESSURE RESERVOIR 1155 Pressure Measurement The manometric study was performed with an indwelling high-fidelity microtransducer catheter (model PC-340 B, Miller Instruments Inc., Houston, Texas) placed in the bile duct by duodenoscopy. The microtransducer was calibrated at 38 C with atmospheric pressure as zero reference before use. Preparation of the patient followed the routine in standard ERCP except for the avoidance of anticholinergic and sedative agents to eliminate their possible effects on the sphincter function. The papilla was identified in the usual manner with a side-view duodenoscope (model JF-1T, Olympus Optical Co., Tokyo, Japan). The 4-m-long microtransducer catheter connected to a control unit (model TCB-100, Miller Instruments) and a pen recorder (model VP-6621A, National Electric Co., Tokyo) was introduced deep into the bile duct. After the intracholedochal position of the catheter was confirmed under fluoroscopy on the prone position, the endoscope was slowly withdrawn over the catheter completely while leaving the catheter in place. The posture of the patient was changed to the supine position and pressure recording was started. Before the recording, the location of the catheter was adjusted to the appropriate position-about the midportion of the common duct-under x-ray control if it was advanced too deep into the intrahepatic duct. A baseline drift of the microtransducer determined at 38 C was minimal, i.e., -0.5 mmhg in 40 min and -1.0 mmhg in 80 min. A pressure tracing was divided into 20-s segments, usually containing five to seven respiratory ~ a r i a teach. i o nan s area undercovered with the tracing Ime was measured by planimetry. An area beneath the predetermined drift curve of the microtransducer at the corresponding time was also measured by planimetry. The mean pressure value was calculated from the value obtained by subtraction of the latter from the former. Simultaneous recording of the duodenal pressure was performed with another microtransducer catheter with the baseline drift of 1.0 mmhg in 40 min and 1.5 mmhg in 80 min. It was placed in the midportion of the duodenum in the same manner as described previously just before the introduction of the bile duct catheter. Pharmacologic Provocation of Sphincter of Oddi Activity After stable basal recording was obtained for 30 min, 0.2 mg/kg of morphine hydrochloride was given intramuscularly to induce SO spasm, and bile duct pressure was monitored for the ensuing 60 min. During this period, respiration and arterial pulsation were simultaneously recorded using a balloon attached to the patient's chest and a microtransducer placed on the radial artery at the wirst when marked morphine-induced changes were noticed on a pressure tracing. At 60 min after the morphine injection, 0.1 J,Lg/kg of caerulein (Farmitalia Laboratories, Milano, Italy) diluted in 5 ml of saline was administered intravenously in 2 min to relax the SO, and the pressure measurement was continued for another 30 min. All procedures were carried out under close observation, and vital signs were frequently checked. Blood Examination To detect any adverse reaction or possible effects on liver function caused by the bile duct pressure elevation, blood samples were obtained for hemanalysis, serum amylase and lipase, serum bilirubin, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and lactic acid dehydrogenase determination at 3 and 18 h after the injection of morphine. Respiration Deep breaths Statistical Analysis Statistical analysis was performed using the Student's t-test for paired data. The difference between means was considered significant if p was <0.05. Results Figure 1. Simultaneous tracings of bile duct pressure, respiration, and arterial pulsation before the administration of morphine. The respiration curve, recorded with a balloon attached to the patient's chest, shows deep breathing and breath holding among normal respiration. The pulsation was registered with a microtransducer catheter placed on the radial artery at the wrist. The intraductal pressure demonstrates relatively regular variations, consisting of a large biphasic change synchronized to and directly influenced by respiration and small waves transmitted from pulsation. The pulsation effect is usually submerged in the large variations but becomes evident during apnea. Factors Affecting Pressure Tracings in the Basal State In an unstimulated condition the bile duct pressure showed relatively regular changes, consisting of a large biphasic variation synchronous to respiration and superimposed small waves transmitted from arterial pulsation (Figure 1). Deep breathing and apnea during the simultaneous recording of the pressure, respiration, and pulsation demonstrated direct influences of the respiration on the pressure tracings in concordance with the earlier report from this department (1). The pulsation effect was the

3 1156 TANAKA ET AL. GASTROENTEROLOGY Vol. B7, No. 5 Table 1. Comparison of Basal Common Bile Duct Pressure Before and After Cholecystectomy in 7 Patients Before cholecystectomyb After cholecystectomyb p value c Time ± ± 0.57 < min 7.6 ± ± 0.56 < 0.02 Pressure at 20 min 7.7 ± ± 0.56 < 0.02 o That is, 30 min before administration of morphine hydrochloride. b Values are mean ± SEM (mmhg). C Paired t-test. 30 min 7.7 ± B ± 0.54 < 0.05 only change noticed on the tracings during breath holding in the basal state. Basal Pressure Before and After Cholecystectomy The pressure in the basal state was completely stable in all 7 patients before cholecystectomy. After the operation, however, initial pressure just after cannulation was found to be slightly elevated in all patients presumably due to SO spasm caused by manipulation of the papilla. The pressure gradually decreased within min and remained stable for the next 30 min. The pressure value after this "adaptation" period, however, was higher than the preoperative level, reaching statistical significance (Table 1). Pressure Responses to Morphine and Caerulein Before and After Cholecystectomy Before cholecystectomy, the administration of morphine caused no noticeable change in the tracings in the patients with a functioning gallbladder, whereas caerulein produced a marked rise of the pressure (Figure 2). This rise was found to coincide with the contraction of the gallbladder seen on an echogram. After cholecystectomy, the pressure was raised and the tracings became irregular in shape and height after the morphine injection. The simultaneous recording during apnea showed the presence of another type of variation not related to either respiration or pulsation (Figure 3) causing the irregularity observed after cholecystectomy, which immediately disappeared after the caerulein administration. As the caerulein is known to produce SO relaxation, this variation is likely to be due to SO spasm. In fact, caerulein injection caused a quick fall of the pressure to the premorphine level as well as the abolishment of the irregularity. Simultaneous tracings of duodenal pressure with bile duct pressure in patients after endoscopic sphincterotomy showed the independent nature of the bile duct pressure and the duodenal pressure (Figure 4). After morphine injection, marked hyperactivity occurred in the duodenum but it did not affect the bile duct pressure, which was stable due to the absence of the SO contraction after the sphincterotomy. Slight increase of the peristaltic activity of mmhg 20 I.M.Morphine 0.2mg/kg I.V.Caerulein 0.1 pg/kg f I I!..... " f j ~. / \ :r I... I... i I I I Itt I I T I N = 7 mean ± SEll ReSpiration Deep breaths Breath holdiog ld 10 JD to 50 &0 10 ID to loa 110 I2D TillE ( min) Figure 2. Bile duct pressure changes in response to morphine followed by caerulein before (e-e) and after (... ) cholecystectomy. Each point is the mean ± SEM from 7 subjects. The postoperative pressure value in the basal state was significantly higher than the preoperative level with p < 0.02 at time O. 10, and 20 min and p < 0.05 at time 30 min. The difference between the values after administration of morphine or caerulein is appar ent. Pulsation ~ t t " W N N o I. W w. w " M " ' ' ' ' I! f Figure 3. Simultaneous recordings of bile duct pressure, respiration, and arterial pulsation after the injection of morphine. Compared with the pressure tracing before morphine shown in Figure 1, the variations are coarse and irregular in shape and height probably due to enhanced effects of respiration and pulsation associated with pressure elevation, and the emergence of another type of wave that appears to be caused by contraction of the sphincter of Oddi as d emonstrated during breath holding.

4 November 1984 GALLBLADDER AS PRESSURE RESERVOIR 1157 mmhi 1.. lorphi"l 0.21I'/kt ~ min a Duodenum 10 I. V. Caerulein 0.1 pg/kg y liin o b Duodenum Figure 4. Changes of pressures in the common bile duct and the duodenum simultaneously recorded in a patient after endoscopic sphincterotomy for the treatment of recurrent stones after cholecystectomy. a. Administration of morphine gave rise to marked hyperactivity of the duodenum but it did not affect the bile duct pressure. b. Thirty minutes after the morphine injection, caerulein was given, causing slight hyperactivity of the duodenum. which had no influence on the bile duct pressure. the duodenum after caerulein administration did not have any influence on the bile duct pressure either. Symptomatic and Biochemical Responses Intracholedochal placement of the microtransducer catheter alone did not cause any symptoms. Some lethargy followed the morphine administration but no abdominal symptoms developed. The injection of caerulein gave rise to nausea of short duration in 2 preoperative and 3 postcholecystectomy patients. A few hours after completion of the investigation 4 of 7 preoperative and 2 postoperative patients had nausea with or without vomiting, which was likely to be a side effect of morphine. No untoward biochemical reaction was noticed in the precholecystectomy patients. In 2 of the 7 postoperative patients, however, transient elevation of transaminase levels possibly arising from the SO spasm occurred, one of which reached sixfold levels of the preprocedure values. All patients including the 2 with the biochemical changes have not developed any symptoms during the follow-up period of mo postoperatively. Discussion The advent of endoscopic manometry of the duodenal papilla enabled us to conduct nonoperative pressure measurement of the SO, pancreatic, and bile ducts (1-5). Two manometric systems are available, i.e., a perfusion method with a side-hole catheter coupled with an external pressure transducer and a microtransducer catheter method. The two systems have both advantages and disadvantages, details of which are discussed elsewhere (1). It

5 1158 TANAKA ET AL. GASTROENTEROLOGY Vol. 87, No.5 should be emphasized that the latter is more suitable for long-term monitoring of in situ bile duct pressure because it does not require fluid infusion in the duct which may cause pressure elevation. Furthermore, prolonged continuous measurement becomes easier by removing an endoscope while leaving a microtransducer catheter in the bile duct (6). In the present investigation, basal pressure before administration of morphine was recorded for > 30 min with the indwelling microtransducer catheter. Although a slight pressure rise was observed immediately after the placement of the catheter in the 7 patients studied postoperatively, the pressure gradually fell and stable recording was invariably obtained after 20 min. This elevation was observed only after cholecystectomy and seemed to be due to a mild spasm of the SO caused by the manipulation of the papilla. The stimulation of the SO with morphine was performed after a stable pressure value was recorded for 30 min following the "adaptation" period, i.e., at least 50 min after the intraductal placement of the catheter. The postoperative basal pressure was significantly higher than that before cholecystectomy. This fact may be one of the possible explanations of the hypothesis of postcholecystectomy bile duct dilation. Because cholangiography was not performed in the present study, it was not proved whether the basal pressure elevation was associated with bile duct dilation. The postoperative study was carried out within 3 wk after cholecystectomy; cholangiographic demonstration of bile duct dilation may have been difficult in such a short time period. Thus, the precise relation of pressure elevation to bile duct dilation after cholecystectomy must await future study. As previously described (1), bile duct pressure showed a relatively regular variation, which consisted of a large biphasic change synchronous to respiration and fine waves transmitted from arterial pulsation. After the morphine injection to induce the SO spasm, the pressure rose and the variation became coarse and irregular in the postcholecystectomy patients, whereas in the patients with a functioning gallbladder no change was noted. A high-speed simultaneous recording of the intraductal pressure, respiration, and pulsation revealed that the irregularity may likely to be caused by the SO spasm. The increased amplitude of the respiratory variation may be due to the enhanced effects of respiration and pulsation with the concomitant presence of the elevation of the intraductal pressure. The morphineinduced changes of the pressure tracing disappeared immediately after the injection of caerulein, a potent sphincter relaxant, suggesting these changes are attributable to the SO spasm. Simultaneous tracings of duodenal pressure in patients with previous endoscopic sphincterotomy demonstrated that increased duodenal pressure after morphine administration did not affect the bile duct pressure even after sphincterotomy, indicating the independent nature of the bile duct pressure and the duodenal pressure. This observation would provide further support to our thesis that the morphine-induced pressure changes are originated from the SO. Caerulein is a decapeptide well known to induce contraction of the gallbladder and relaxation of the SO. Many studies were reported on its actions in experimental animals (7-9), but only a few in humans (10,11). In the present investigation, a slow bolus injection of 0.1 jlg/kg of caerulein immediatedly relaxed the SO, resulting in a quick fall of the bile duct pressure that had been elevated 60 min after the administration of morphine in the postcholecystectomy patients. This is in accordance with the observation in guinea pigs reported by Agosti et al. (9), in which they found that caerulein is the most potent relaxant, 20 times as potent as cholecystokinin, to the SO spasm caused by morphine. In patients with a functioning gallbladder, however, the caerulein-induced pressure reduction was overwhelmed by a marked rise of the intraductal pressure caused by contraction of the gallbladder. The pressure elevation as a net effect of caerulein on the human biliary tract was consistent with the findings of the endoscopic manometric study on the effect of cholecystokinin by Eberhardt et al. (12). In the presence of the SO spasm induced by morphine, the patients after cholecystectomy showed considerable increase in the bile duct pressure as well as the changes in the shape and height of the tracing waves. However, such pressure elevation was not observed in those with a functioning gallbladder, suggesting its role as a pressure reservoir. This finding has important implications in an assessment of the morphine or morphine-prostigmin test in diagnosing SO stenosis. If a rise in transaminase levels caused by morphine-provoked obstruction to the bile flow is taken as a criterion for a positive test (13), the presence of an intact gallbladder induces a falsely negative result because it acts as a pressure reservoir and eliminates such an effect. The pressure reservoir function of the gallbladder was mentioned as early as 1962 by Ong (14). In a statement for indication of cholecystectomy in patients with pyogenic cholangitis undergoing choledocholithotomy and sphincteroplasty Ong pointed out that cholecystectomy is not necessary and may even be harmful because the gallbladder might regulate bile duct pressure by dilation if there should be an obstruction at the distal common bile duct. It is clear from the present study that a loss of the

6 November 1984 GALLBLADDER AS PRESSURE RESERVOIR 1159 pressure reservoir function of the gallbladder accounts for the intraductal pressure elevation in response to morphine after cholecystectomy. The clinical significance of this phenomenon is to provide a possible explanation for a development of so-called postcholecystectomy syndrome. Spasm of the SO, if it occurs in a postcholecystectomy patient, readily leads to an elevation of the bile duct pressure, giving rise to biliary pain in some cases. Although the pressure elevation induced by morphine was not associated with pain in the postcholecystectomy patients studied herein, our previous study demonstrated that morphine injection caused pain in patients with suspected postcholecystectomy syndrome (6). Whether the bile duct manometry combined with morphine provocation can aid the diagnosis of postcholecystectomy syndrome remains speculative at present. References 1. Tanaka M. Ikeda S, Nakayama F. Nonoperative measurement of pancreatic and common bile duct pressures with a microtransducer catheter and effects of duodenoscopic sphincterotomy. Dig Dis Sci 1981;26: Nebel ~ T Manometric. evaluation of the papilla of Vater. Gastrointest Endosc 1975;21: Hogan WI. Dodds WJ, Geenen JE, Schaffer RD, Stewart ET, Arndorfer RC. Sphincter of Oddi motor activity in man: a zone of unique, phasic high-pressure contractions. In: Duthie HL, eds. Gastrointestinal motility in health and disease. Lancaster, England: MTP Press,1978: Funch-Jensen P, Csendes A, Kruse A, Oster MJ, Amdrup E. Common bile duct and Oddi sphincter pressure before and after endoscopic papillotomy in patients with common bile duct stones. Ann Surg 1979;190: Geenen JE, Hogan WJ, Dodds WI. Stewart ET, Arndorfer RC. Intraluminal pressure recording from the human sphincter of Oddi. Gastroenterology 1980;78: Tanaka M, Ikeda S, Nakayama F. Continuous measurement of common bile duct pressure with an indwelling microtransducer catheter introduced by duodenoscopy: new diagnostic aid for postcholecystectomy dyskinesia. A preliminary report. Gastrointest Endosc 1983;29: Bertaccini G, DeCaro G, Endean R, Erspamer U, Impicciatore M. The action of caerulein on the smooth muscles of the gastrointestinal tract and the gallbladder. Br J Pharmacol 1968;34: Bertaccini G, Gallarini G, Agosti A, Zaunetti G. Action of caerulein on the biliary system of the dog. Arch Int Pharmacokyn 1970;183: Agosti A, Mantovani P, Mori L. Action of caerulein and related substances on the sphincter of Oddi. Naunyn Schmiedebergs Arch Pharmacol 1971;268: Bertaccini G, Braibanti T, Uva F. Cholecystokinetic activity of the new peptide caerulein in man. Gastroenterology 1969; 56: Bertaccini G. Agosti A. Action of caerulein on intestinal motility in man. Gastroenterology 1971;60: Eberhardt G, Heilmann S, Szeoke S. Einfluss von Caerulein auf endoskopisch gemessene Druckwerte im Ductus choledochus un Duodenum. Z Gastroenterol 1977;15: Madura JA, McCammon RL, Paris JM, Jesseph JE. The Nardi test and biliary manometry in the diagnosis of pancreaticobiliary sphincter dysfunction. Surgery 1981;90: Ong GB. A study of recurrent pyogenic cholangitis. Arch Surg 1962;84: