ceruletide and Cholecystitis

The purpose of this study was to investigate the utility of repeated applications of ceruletid to reduce gallbladder volume and its feasibility as a means of prophylaxis of acute acalculous cholecystitis in intensive care patients. First, a dose-response curve of ceruletid was obtained in 20 mechanically ventilated patients of a surgical intensive care unit (SICU) not receiving enteral nutrition. An effective dose of ceruletid, defined by a 50% reduction of gallbladder volume was established and subsequently studied in 40 mechanically ventilated SICU patients on total parenteral nutrition in a prospective, randomized, controlled, triple-blind trial. Gallbladder volume, sludge formation and side effects were evaluated. A dose of 1.5 micrograms/kg body weight ceruletid was established as the effective dose, causing 50% reduction of gallbladder volume in all patients studied and reduction of gallbladder sludge in 95%. In 67.5% of patients side effects were observed, requiring therapeutic intervention in 68%. It is concluded that ceruletid is effective in stimulating gallbladder contraction and reducing sludge formation in severely ill patients on intensive care units. Its routine use as prophylaxis of acute acalculous cholecystitis, however, may be limited by the nature, severity and frequency of side effects.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Ceruletide; Cholecystitis; Critical Care; Dose-Response Relationship, Drug; Female; Gallbladder; Gastrointestinal Agents; Humans; Male; Middle Aged; Multivariate Analysis; Prospective Studies

The incidence of acute acalculous cholecystitis (AAC) is increasing and associated mortality is high. Biliary stasis and sludge formation are probably important factors in the pathogenesis of this disease. No data concerning the dynamics of these changes in the early phase of intensive care therapy are available. The gallbladders of 20 patients treated after major abdominal surgery in the surgical intensive care unit (SICU) with mechanical ventilation and without enteral feedings were therefore observed sonographically during the first 5 postoperative days in a prospective observational study. 20 patients treated on a regular ward after major abdominal surgery also not receiving any enteral nutrition served as control group. 24 hours after admission to the intensive care unit and on all subsequent days of observation the gallbladders of the patients in the SICU-group were significantly larger than in the control group. Sludge also appeared earlier and more frequently in the gallbladders of the SICU-patients. Lack of enteral feedings alone cannot explain these results. Positive-pressure ventilation and medications used in SICU are most likely responsible for the observed differences. Besides the necessity to make the diagnosis of AAC as early as possible, it appears to be worthwhile to investigate measures of prophylaxis. Since gallbladder distension in patients treated in SICU can be already observed on the first postoperative day it seems to be reasonable to initiate a regimen of prophylactic measures (e.g. with cholecystokinin or ceruletide) early in the course of ICU-therapy.

Topics: Abdomen; Acute Disease; Aged; Biliary Dyskinesia; Ceruletide; Cholecystitis; Cholecystokinin; Critical Care; Female; Humans; Male; Middle Aged; Parenteral Nutrition, Total; Positive-Pressure Respiration; Postoperative Complications; Prospective Studies; Risk Factors; Ultrasonography

The effects of single and repeated short-term (4 hr) obstruction of pancreaticobiliary duct (PBDO), with or without exocrine stimulation (intraductal hypertension) by cerulein infusion (0.2 micrograms/kg.hr), on the exocrine pancreas were evaluated in the rat. Single blockage of pancreaticobiliary duct for 4 hr caused a significant rise in serum amylase levels, pancreatic water content, and redistribution of lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction, which was considered to mean the colocalization of lysosomal enzymes with pancreatic digestive enzymes in the same subcellular compartment in acinar cells. In addition, the accelerated lysosomal and mitochondrial fragility was observed in the single pancreaticobiliary-duct-obstructed animals. Moreover, the repeated PBDO for 4 hr (2 hr in each obstruction and 1 hr of free flowing of pancreaticobiliary juice between two obstructions) caused more marked changes in almost the all parameters, and the repeated PBDO with intraductal hypertension caused an activation of trypsinogen in the pancreas, making more marked changes in almost the all parameters than the repeated PBDO only group. These results indicate that the present model of repeated PBDO with exocrine stimulation seems to be a pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries induced by PBDO, particularly by repeated PBDO with exocrine stimulation, probably via activation of trypsinogen to trypsin by lysosomal enzyme, cathepsin B.

Topics: Acute Disease; Amylases; Animals; Body Water; Cathepsin B; Ceruletide; Cholecystitis; Cholelithiasis; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar; Trypsin; Trypsinogen

The increased incidence of gallbladder diseases after gastrectomy is discussed with regard to contractile motility of the gallbladder. Ultrasonographic findings and contraction of the gallbladder in response to egg yolk or caerulein were studied before and after gastrectomy at intervals ranging from 2 weeks to 6 months. Enlargement of the gallbladder with accumulation of biliary sludge and hypomotility were frequently observed within a month of operation for gastric cancer, suggesting that biliary stasis is an important contributing factor in postoperative acute cholecystitis. Within 3 months of operation, contraction had recovered to close to preoperative levels and the incidence of biliary sludge formation gradually decreased. Daily administration of an opiate antagonist, naloxone (0.8 mg), significantly improved gallbladder dyskinesia and decreased the incidence of biliary sludge formation within 1 month of gastrectomy.

Topics: Acute Disease; Ceruletide; Cholecystitis; Egg Yolk; Gallbladder; Gastrectomy; Humans; Middle Aged; Muscle Contraction; Naloxone; Postoperative Complications; Stomach Neoplasms

To determine the sites and mechanisms of action of cholecystokinin-octapeptide (CCK-OP) on the human gallbladder, effects of atropine sulfate on CCK-OP-evoked contractions were studied in both in vivo and in vitro experiments. In vivo studies performed by means of real time ultrasonography in six healthy volunteers showed remarkable contractions of the gallbladder after intramuscular injection of CCK-OP (0.07 microgram/kg), which was nearly abolished by premedication of atropine sulfate (0.015 mg/kg). Atropine sulfate (10(-6) M) slightly but significantly reduced CCK-OP (10(-11) M-3 X 10(-7) M) induced contractions and the dose-response curve for CCK-OP was shifted to the right of the muscle strips of the human gallbladders. It is suggested that CCK-OP acts mainly on cholinergic neurons in vivo. On the contrary, the most sensitive sites of action of CCK-OP might be smooth muscles rather than cholinergic neurons in vitro.

Topics: Adult; Atropine; Ceruletide; Cholecystitis; Dose-Response Relationship, Drug; Egg Yolk; Gallbladder; Humans; In Vitro Techniques; Male; Muscle Contraction; Sincalide; Ultrasonography

The functional activity of the sphincter of Oddi complex has been examined by ceruletide manometry in patients undergoing cholecystectomy with a normal peroperative cholangiogram. In Group I (n = 14), which included patients with previous acute cholecystitis/biliary colic, the sphincter activity appeared to be normal and responded to intravenous ceruletide by a marked relaxation with a significant fall in both the infusion and postinfusion pressures. In patients undergoing cholecystectomy for gallstone-associated pancreatitis (n = 8), the sphincter exhibited manometric features of hypotonia with low infusion and postinfusion pressures which were not significantly altered by intravenous ceruletide.

Topics: Acute Disease; Adult; Aged; Ampulla of Vater; Ceruletide; Cholecystectomy; Cholecystitis; Cholelithiasis; Colic; Common Bile Duct; Humans; Manometry; Middle Aged; Pancreatitis; Sphincter of Oddi