Toxicology Brief: The critical care of aflatoxin-induced liver failure in dogs - Veterinary Medicine
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Toxicology Brief: The critical care of aflatoxin-induced liver failure in dogs


VETERINARY MEDICINE


Control of hemorrhage

An immediate and life-threatening concern in dogs with aflatoxicosis is an increased bleeding tendency resulting from hepatocellular damage and decreased synthesis of coagulation factors, which creates a hypocoagulable state. Constant-rate infusions of fresh frozen plasma may be indicated to supplement coagulation factors. If the patient is moderately to severely anemic, fresh whole blood is preferred.4,13,43

In addition to decreased production of coagulation factors, a vitamin K deficiency may contribute to the coagulation deficiencies seen with aflatoxicosis. On histologic examination of liver samples from dogs with aflatoxicosis, bile canaliculi are sometimes plugged with casts. Biliary obstruction interferes with the bile-salt facilitated absorption of lipid-soluble vitamin K. Moreover, aflatoxin is a coumarin-like derivative and may have a direct inhibitory effect on vitamin K activity.4

Vitamin K is an essential cofactor in the activation of coagulation factors II, VII, IX, and X, as well as anticoagulant proteins C and S. Thus, a vitamin K deficiency may contribute to the hypocoagulable state in patients with aflatoxicosis. Treatment with vitamin K1 has been shown to improve, though not resolve, the coagulation abnormalities. Vitamin K should be given at a dose of 1 to 5 mg/kg either subcutaneously or orally, although subcutaneous administration is preferred because of decreased gastrointestinal absorption of oral vitamin K.44,45

Another reason for increased bleeding tendencies in patients with aflatoxicosis is enteric hemorrhage incited by portal hypertension. Histologic examination of tissue samples from dogs with aflatoxicosis reveals hepatic outflow occlusion and portal fibrosis, and the gastrointestinal tract shows resultant mucosal congestion, edema, and hemorrhage. Dogs with aflatoxicosis may exhibit hematochezia, melena, and hematemesis.4,13,15,17 Blood loss from the gastrointestinal tract and hemorrhagic effusions into the abdomen can lead to anemia.16,18 Packed red blood cells, bovine hemoglobin glutamer-200 (Oxyglobin—Biopure), or whole blood may be administered to increase oxygenation and blood volume, but these products will not decrease the portal hypertension.43,46

Finally, DIC has been reported in several cases of canine aflatoxicosis.18 The inciting cause of DIC in cases of acute hepatitis or liver failure is thought to be tissue procoagulants released into circulation from damaged hepatocytes.45 The combination of increased consumption of coagulation factors from DIC and reduced synthesis and activation of coagulation factors in aflatoxicosis may lead to severe hemorrhage. Fresh whole blood or fresh frozen plasma would be indicated in these cases, but unfortunately, patients with hemorrhagic signs have extremely poor prognoses.18

Antibiotics

Because of a compromised gastrointestinal barrier in acute liver disease, patients with aflatoxicosis have an increased risk of bacteremia and sepsis. Using antibiotics directed toward gram-negative bacteria is suggested. Metronidazole can be used in combination with amoxicillin, ampicillin, cephalexin, or cefadroxil. Metronidazole is effective against gram-negative anaerobes that produce ammonia, so it may help prevent hepatoencephalopathy as well as sepsis.43 Because metronidazole is metabolized by the liver and has been reported to cause hepatotoxicosis, reducing the dosage by 50% (to 5 mg/kg twice a day) may be appropriate in patients with aflatoxicosis.47

Antiemetics and gastrointestinal protectants

Patients with aflatoxicosis frequently pre sent with a history of progressive vomiting. A constant-rate infusion of metoclopramide is a good choice for initially treating these animals. If the vomiting is refractory to treatment with metoclopramide, adding a serotonin antagonist such as dolasetron or ondansetron may provide relief. Also consider sucralfate, famotidine, and other gastrointestinal protectants in patients with aflatoxicosis to manage ulceration and decrease acid in the gastrointestinal tract.13,43

Control of hepatoencephalopathy

In patients showing signs of hepatoencephalopathy, medications such as lactulose, neomycin sulfate, metronidazole, and flumazenil may be warranted. More information on treating hepatoencephalopathy in patients with acute liver failure is found elsewhere.43


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Source: VETERINARY MEDICINE,
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