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Systemic endotoxaemia following obstructive jaundice: the role of lactulose.

BACKGROUND: Obstructive jaundice is often accompanied by bacterial translocation and subsequent sepsis. The effect of lactulose in preventing that process was evaluated in an experimental model. Obstructive jaundice was induced in 23 rabbits after common bile duct ligation. METHODS: Animals were divided into two groups. Group A of 11 animals-controls and group B of 12 rabbits, which received 2 ml/kg of lactulose p.o. by a nasogastric tube. Blood was sampled daily, before and after operation. Samples were applied for culture and for estimation of endotoxins (LPS), tumor necrosis factor (TNFa), and malondialdehyde (MDA). RESULTS: Mean (+/-SD) survival of animals of group A was 3.08+/-0.19 days compared to 5.36+/-0.41 days of animals of group B. Serum concentrations of LPS and TNFa of each day of treatment remain constant in animals of group A; they were steadily decreased in animals of group B reaching statistical significance on the fourth day. Similar changes were not found for MDA. CONCLUSION: The administration of lactulose may prevent systemic endotoxaemia and the subsequent inflammatory response in an experimental model of obstructive jaundice, so as to extend survival. These results merit further clinical evaluation.

Acute Disease↗

Carbohydrate tolerance and insulin responses in obstructive jaundice.

Twenty-three patients with obstructive jaundice were given a 50-g oral glucose tolerance test (G.T.T.) and an insulin stimulation test with oral glucose and intravenous tolbutamide and glucagon. An abnormal glucose response was as common in patients with carcinoma of the pancreas (seven out of 12) as in patients with "other" causes of obstructive jaundice (six out of 11). Though both groups had a low and delayed insulin response the insulin levels were significantly lower in patients with carcinoma of the pancreas. After the insulin stimulation test patients with obstructive jaundice who did not have carcinoma of the pancreas had a greater and significantly different insulin response from patients with pancreatic cancer. There was, however, considerable overlapping between the results of individual patients in the two groups.

Aged↗

Accuracy of sonography and transhepatic chloangiography in obstructive jaundice.

Fifty patients with obstructive jaundice were studied by both ultrasonography and percutaneous transhepatic cholangiography (P)TC). Comparison was made of the relative accuracy of sonography and transhepatic cholangiography in delineating both the site and cause of the jaundice. The site of obstruction was defined in 86% by sonography and in 100% by PTC. Etiology was defined in 52% by sonography and in 86% by PTC. Using both modalities the etiology was evident in 94% of patients. Percutaneous transhepatic cholangiography should be reserved for those patients in whom sonography does not identify the site and cause of the obstruction.

Aged↗

Extrahepatic portal venous obstruction and obstructive jaundice: approach to management.

BACKGROUND: Patients with long-standing extrahepatic portal venous obstruction (EHPVO) develop extensive collaterals in the hepatoduodenal ligament as a result of enlargement of the periportal veins. These patients are also prone to develop obstructive jaundice as a result of strictures and/or choledocholithiasis. Surgical management of obstructive jaundice in such patients becomes difficult in the presence of these collaterals. AIM: To review the approach to management of patients with EHPVO and obstructive jaundice. METHODS: Retrospective review of patients with EHPVO and obstructive jaundice requiring surgical and/or endoscopic management between 1992 and 2002. RESULTS: Thirteen patients (nine males, aged 12-50 years) with EHPVO and obstructive jaundice were evaluated. No patient had underlying cirrhosis or hepatocellular carcinoma. Five patients (group A) had biliary stricture; three (group B) had choledocholithiasis; and five (group C) had biliary stricture with choledocholithiasis. Primary surgical management was performed in group A (portosystemic shunt in four-strictures resolved in three; hepaticojejunostomy in one). In group B (n = 3) endoscopic stone extraction was successful in two patients. One patient underwent staged procedure (portosystemic shunt followed by biliary surgery). In group C, initial endoscopic management failed in four patients in whom it was attempted. All five patients thereafter underwent surgery (staged procedure, one; choledochoduodenostomy, one; devascularization, one; abandoned, two). Repeat postoperative endoscopic management was successful in two of the group C patients. Overall (group B and C), massive intraoperative hemorrhage occurred in three patients (one died). Postoperative hemorrhage occurred in one patient. CONCLUSION: In patients with EHPVO and obstructive jaundice, primary biliary tract surgery has significant morbidity and mortality. Endoscopic management should be the preferred modality. In patients with endoscopic failure, a staged procedure (portosystemic shunt followed by biliary surgery) should be preferred. Strictures alone may resolve after a portosystemic shunt. Endoscopic stenting may be required as an adjunct.

Adolescent↗

Influence of obstructive jaundice on gastric mucosal barrier in dogs.

The influence of obstructive jaundice on the gastric mucosal barrier was studied before and after ligation of the common bile duct using 21 mongrel dogs with a Heidenhain pouch. The gastric mucosal barrier was examined using gastric mucosal permeability of ionic net fluxes of Na+ and H+ (delta Na+, delta H+), and transmucosal electrical potential difference (PD) during the irrigation of the pouch with various test solutions. No significant differences in delta Na+ or delta H+ during the irrigation with 100 mN HCl were found between before and after obstructive jaundice. Almost the same results were observed during the irrigation with 150 mN HCl. Obvious increases in delta Na+ and delta H+ were found, when 20 mM sodium taurocholate (taurocholate) was used in addition to 100 mN HCl. No differences were, however, found between before and after obstructive jaundice. The PD during the irrigation with 100 and 150 mN HCl showed about the same levels of -50 mV. The PD decreased early during the irrigation with 20 mM taurocholate in addition to 100 mN HCl, but no differences were found in these values between before and after obstructive jaundice. Dose-response relationships were found between the concentration of taurocholate in addition to 100 mN HCl, and delta Na+, delta H+ and sigma PD/15 min, while no differences in ED50 of taurocholate for delta Na+, delta H+ or sigma PD/15 min were observed between before and after obstructive jaundice. These results suggest that obstructive jaundice itself exerts no influence on the gastric mucosal barrier with respect to gastric mucosal permeability and PD in dogs.

Animals↗

Altered serum transforming growth factor-beta1 and monocyte chemoattractant protein-1 levels in obstructive jaundice.

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-beta1 (TGFbeta1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFbeta1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFbeta1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFbeta1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFbeta1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFbeta1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.

Animals↗

Obstructive jaundice blunts myocardial contractile response to isoprenaline in the dog: a clue to the susceptibility of jaundiced patients to shock?

Patients with obstructive jaundice are susceptible to postoperative shock. To clarify the mechanism of this phenomenon, we compared the contractile response to isoprenaline of isolated ventricular preparations from three groups of dogs: (a) dogs with chronic bile-duct ligation (CBDL), (b) dogs with choledochocaval anastomosis (CDCA) and (c) sham-operated dogs (SO). Isolated ventricular muscles from CBDL and CDCA dogs showed a depressed contractile response to isoprenaline as compared with SO dogs. Mechanical performance was spared in the CBDL and CDCA dogs. There were no differences in the contractile responses of SO and CBDL dogs, either to ouabain or to changes in the rates of stimulation (force-frequency relationships). These data demonstrate that, in the dog, obstructive jaundice and/or cholaemia are associated with blunted contractile response to beta-adrenoreceptor stimulation in the face of intact basic mechanical performance. Similar inotropic refractoriness to beta-adrenoreceptor stimulation could contribute to the susceptibility to postoperative shock in patients with obstructive jaundice.

Alanine Transaminase↗

Renal failure complicating obstructive jaundice.

Postoperative acute renal failure in patients with obstructive jaundice remains a clinically significant complication. Acute renal failure occurs in approximately 9 percent of patients requiring surgery for relief of obstructive jaundice, and contributes to eventual mortality in 76 percent of those who develop it. The overall mortality rate for patients undergoing surgery for obstructive jaundice is 16 percent. Despite advances in perioperative care, these figures have changed very little over the past 25 years. This article describes the clinical association between jaundice and renal failure and reviews the studies that have contributed to the delineation of the possible underlying pathophysiologic mechanisms, as well as possible preventive measures which have been developed as a result of these investigations. With increased awareness of the potential risk of developing postoperative acute renal failure, the institution of prophylactic measures may result in an improvement in the mortality rate seen after surgery for obstructive jaundice.

Acute Kidney Injury↗