Simultaneous non-traumatic perforation of the extrahepatic bile duct and the gallbladder is an uncommon occurrence that has been infrequently reported. We describe a patient with a spontaneous perforation of both the extrahepatic bile duct and the gallbladder. A contrast-enhanced computed tomography (CECT) scan of the abdomen and endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a perforation of the gallbladder and a free leak from the right hepatic duct, respectively. Endoscopic biliary drainage following a sphincterotomy and biliary stent placement led to a dramatic improvement in the patient’s general condition. He was subsequently scheduled to undergo an elective cholecystectomy. Repeat ERCP performed at 4 weeks after the initial stenting showed a normal cholangiogram and a distally migrated stent, which was there after removed. However, early stent removal led to re-perforation of hepatic duct and gallbladder. A repeat endoscopic biliary drainage did not help, and the patient developed biliary peritonitis. Surgical exploration revealed a perforation at the fundus of the gallbladder, 400 ml of biliopurulent collection and a frozen Calot’s triangle. A subtotal cholecystectomy, gall stone removal, and a thorough peritoneal lavage were undertaken. The patient improved postoperatively. The second biliary stent was removed after 4 months. This case report highlights the role of endoscopic biliary drainage in the management of an extrahepatic bile duct perforation and warns against the early removal of a biliary stent.

OBJECTIVETo investigate the effects of pre-treatment of alpha-ketoglutarate (alpha-KG) on cyanide-induced lethality and changes in various physiological parameters in rodents.

METHODSThe LD50 of potassium cyanide (KCN) given orally (po), intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was determined in male mice, in the presence or absence alpha-KG given po, ip or iv. alpha-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index (PI) was calculated as the ratio of LD50 of KCN in the presence of alpha-KG (protected animals) and LD50 of KCN in the absence of alpha-KG (unprotected animals). In a separate experiment, several physiological variables viz. mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular transmission (NMT) and rectal temperature (RT) were measured in anesthetized female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) alpha-KG and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50) doses of KCN (po).

RESULTSPI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with a-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg alpha-KG given ip (-10 min), respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg alpha-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg alpha-KG given po at -10, -20 or -40 min, respectively. No appreciable protection was observed when lower doses of alpha-KG (ip or po) challenged KCN given by sc route. Pre-treatment of iv or po administration of alpha-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of alpha-KG (po; 2.0 g/kg). However, no protection was observed on NMT. Protective efficacy of alpha-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN. Decrease in MAP and NMT caused by 2.0 LD50 KCN (po) was resolved by iv administration of alpha-KG.

CONCLUSIONSCyanide antagonism by alpha-KG is best exhibited when both alpha-KG and KCN are given by po route. The protective effect of a-KG on cyanide-induced changes in several physiological parameters also indicates a promising role of alpha-KG as an alternative cyanide antidote.

Administration, Oral ; Animals ; Antidotes ; administration & dosage ; Dose-Response Relationship, Drug ; Female ; Injections, Intraperitoneal ; Injections, Intravenous ; Injections, Subcutaneous ; Ketoglutaric Acids ; administration & dosage ; Lethal Dose 50 ; Male ; Mice ; Potassium Cyanide ; poisoning ; Rats ; Rats, Wistar