The cause of the hepatic necrosis is unknown. One possible mechanism is that xylitol and its metabolites deplete adenosine
triphosphate in the liver.19,20 Without adequate adenosine triphosphate, the liver is unable to maintain normal cellular function, and cellular necrosis
results. Another mechanism may involve the production of reactive oxygen species that can damage cellular components.21
ARE OTHER SWEETENERS SAFE IN DOGS?
Other sugar alcohols such as sorbitol and mannitol have little to no effect on blood glucose concentrations or insulin secretion
in dogs,6 although over-ingestion may result in an osmotic diarrhea. Artificial sweeteners, such as saccharin, aspartame, and sucralose,
are generally regarded as safe and should not cause significant illness if large amounts are ingested.22
Common causes of hypoglycemia in dogs include parenteral insulin overdose, oral hypoglycemic drugs such as glipizide or glyburide,
juvenile hypoglycemia, hunting dog hypoglycemia, pancreatic beta-cell tumor (insulinoma), and idiopathic causes.23 Acute hepatic necrosis in dogs can be caused by ingestion of acetaminophen, aflatoxins, Amanita phalloides and similar hepatotoxic mushrooms, blue-green algae, iron, and sago palms (Cycas species).24,25 In addition, acute hepatic necrosis can be caused by infectious diseases (e.g. infectious canine hepatitis, leptospirosis, mycoses, toxoplasmosis), trauma, and heatstroke.25
Based on experience at the aspca apcc, dogs ingesting > 0.1 g/kg of xylitol should be considered at risk for developing hypoglycemia,
while doses of > 0.5 g/kg may be hepatotoxic. Calculating the xylitol dose for gum products can be difficult. While some gum
products specify their xylitol content, it is more likely that only the total sugar alcohol content will be listed on the
label. In most gum products, several different sugar alcohols (including sorbitol, isomalt, maltitol, and mannitol) may be
present, making it difficult to determine xylitol content. If xylitol is the first sugar alcohol in the ingredient list, then
the dose should based on the total amount of sugar alcohols per piece even though this will result in an overestimation of
the xylitol dose. If xylitol is not the first listed sugar alcohol, I recommend that 0.3 g of xylitol per piece of gum be
used to estimate the xylitol dose. For powdered xylitol and home-baked goods, 1 cup of xylitol weighs about 190 g.
Since the onset of signs can be rapid, emesis should be attempted only if the animal is asymptomatic. Activated charcoal is
not likely to beneficial. In one in vitro experiment, activated charcoal was found to bind a low percentage of xylitol, and
the binding was pH-dependent.26 If a dog ingests between 0.1 and 0.5 g/kg of xylitol, hospitalize the dog and obtain baseline glucose, potassium, phosphorus,
and total bilirubin concentrations; liver enzyme activities; and coagulation measurements. Monitor blood glucose concentrations
every one to two hours for at least 12 hours, and recheck the other tests every 24 hours for at least 72 hours.
If hypoglycemia develops, administer a 1- to 2-ml/kg bolus of 25% dextrose intravenously followed by intravenous fluids containing
2.5% to 5% dextrose in order to maintain normal glucose concentrations. Correct severe hypokalemia (< 2.5 mEq/L) by adding
potassium to the fluids. Treatment may be needed for 12 to 24 hours or until glucose concentrations can be maintained without
For exposures of > 0.5 g/kg, the treatment is the same as outlined above except I recommend that dextrose treatment be started
immediately, whether or not hypoglycemia has occurred. Liver protectants and antioxidants such as N-acetylcysteine (140 to
280 mg/kg loading dose followed by 70 mg/kg intravenously or orally q.i.d.), S-adenosylmethionine (Denosyl—Nutramax; 17 to
20 mg/kg/day orally), silymarin (Marin [Silybin]—Nutramax; 20 to 50 mg/kg/day orally), or vitamin E (100 to 400 IU orally
b.i.d.) may be useful, although their efficacy in this toxicosis has not been established. Plasma transfusions, blood transfusions,
or both may be needed if a coagulopathy develops.