Toxic effects of intrahepatic reflux of monooctanoin in a canine model.
Monooctanoin (MO), when infused into the common bile duct (CBD), is an effective agent in dissolving retained CBD stones. If the stone migrates and obstructs the distal CBD, the solution could be infused under pressure resulting in intrahepatic reflux. The relationship between the infusion pressure and the safety of monooctanoin has not been evaluated. To study the effects of intrahepatic reflux of MO, a canine model was used and solutions were infused into an obstructed CBD under controlled pressure. Solutions of normal saline (NS), 150 mM sodium cholate (Ch), or MO were infused under pressures of 30, 40, and 50 cm. All of eight dogs died when infused with MO at 50 cm pressure with a mean administered dose of 1.4 +/- 0.4 cc/kg within a mean time of 87 +/- 38 min. Three of four dogs died at 40 cm pressure (1.7 +/- 0.4 cc/kg; 133 +/- 95 min) and only one of three dogs died at 30 cm pressure (2.5 cc/kg; 335 min). These dogs died from progressive hypoxia, acidosis, hemolysis, and hemorrhagic pneumonitis. Four dogs each were administered Ch at 50 and 40 cm pressure and all died with an average absorption of 19 cc/kg. Six dogs were tested with NS at 50 cm and all survived despite absorbing 180 cc/kg in 6 hr. MO at 50 cm pressure and Ch at both 40 and 50 cm pressure were significantly more toxic than saline. It is concluded that MO and Ch infused under pressure into CBD carry a significant risk of serious side effects. The infusion pressure must be monitored to prevent increased biliary pressure which might lead to intrahepatic reflux.
D000818:Animals; D001655:Bile Reflux / Q000209:etiology*; D001660:Biliary Tract Diseases / Q000209:etiology*; D002210:Caprylates; D002769:Cholelithiasis / Q000188:drug therapy; D002779:Cholestasis / Q000150:complications; D019826:Cholic Acid; D002793:Cholic Acids / Q000008:administration & dosage / Q000633:toxicity; D003137:Common Bile Duct Diseases / Q000150:complications; D004285:Dogs; D005989:Glycerides / Q000008:administration & dosage* / Q000633:toxicity; D008954:Models, Biological; D011312:Pressure; D012997:Solvents
D002210:Caprylates; D002793:Cholic Acids; D005989:Glycerides; D012997:Solvents; D019826:Cholic Acid; C025343:monooctanoin