Potential toxins for "in town" pets (Proceedings)

Xylitol poisoning is a recently recognized problem in dogs. Xylitol is a five carbon sugar alcohol [pentitol] that is used as a sugar substitute. Dogs can become poisoned from the ingestion of baked goods [added risk of theobromine if chocolate is consumed], desserts, gum, candy, toothpaste and other oral care products. Ingestion of as little as 0.15 g/kg BW can lead to hypoglycemia, and dogs ingesting > 0.5 g/kg run risks of developing hepatic disease. Dogs developing hepatic disease may not show any evidence of hypoglycemia early on.

Calculating the xylitol content in products such as gums may be difficult, in that some labels only list the total sugar alcohol content and not the specific xylitol content. In general, if xylitol is the first sugar alcohol listed in the ingredients, then base the estimated exposure dose on the total amount of sugar alcohols per weight of material. If xylitol is not the first ingredient listed, it has been recommended that 0.3 g of xylitol per piece of gum be used to estimate exposure dose. For exposures involving powdered xylitol and baked goods, 1 cup of xylitol weighs about 190 g.

Consumption of excessive xylitol in all pets can cause diarrhea and the production of excess intestinal gas. However, exposures in the dog cause a severe increase in insulin release from the pancreas leading to a precipitous decline in blood sugar. Other differentials for hypoglycemia in the dog include insulinoma, sepsis and severe hepatic disease. The hypoglycemia is typically observed within 30 to 60 minutes following ingestion, and can be delayed for several hours. Clinically the dog may display weakness, ataxia and seizures. Within 9 to 72 hours, hepatic failure may be observed, so several serum chemistry panels should be run post exposure to monitor for this occurrence. Clinical signs of hepatic disease can include weakness, depression, vomiting, lethargy, presence of petechial and ecchymotic hemorrhages, abdominal tenderness, hemorrhages as a result of abnormal clotting times, recumbency and seizures.

Elevated liver enzymes, hyperbilirubinemia, hypokalemia, hyperphosphatemia, prolonged clotting times, thrombocytopenia and hyperphosphatemia have been reported in dogs suffering from liver disease. Microscopically, diffuse hepatic necrosis with biliary hyperplasia is seen. Treatment of the asymptomatic patient should include emesis and possibly a cathartic. Oral sugar supplementation has been suggested prophylactically to avoid the hypoglycemia from occurring. A 25% dextrose bolus, IV [later with fluids, 2.5-5%] should be used to control the hypoglycemia, and potassium may be necessary to add to control the hypokalemia. Glucose measurements should be taken hourly, for up to 24 hours or until the patient has been stabilized. Hepatic protectants and antioxidants, such as n-acetylcysteine [140-280 mg/kg loading dose IV, PO; followed by 70 mg/kg qid], vitamin K1 [1.25-2.5 mg/kg PO bid] plasma, SAME [20 mg/kg/day PO], vitamin E [100-400 IU bid PO] and silymarin [20-50 mg/kg/day PO], can be used in the patient with liver disease. There is no analytical assay present for xylitol in biological specimens at this time, so the diagnosis relies heavily on potential history for exposure.

Alcohol poisoning is a relatively frequent poisoning observed in dogs. Many pets surprisingly enjoy the taste of alcohol containing products, and some people have been known to intentionally get a pet 'drunk' to see how the pet will act. Luckily, most dogs recover uneventfully from these episodes, but some exposures appear to contain more risks. One in particular is dogs ingesting fermented raw bread dough. The yeast added to bread dough converts the carbohydrates to alcohol and in the process, carbon dioxide is released which makes the dough rise. This same reaction occurs in the stomach once the bread dough is swallowed. Not only can this result in alcohol overload [causing ataxia, depression, weakness, drunkenness, hypothermia, respiratory depression, stupor, coma], but the gastric distension can cause respiratory and vascular compromise. Radiographs reveal marked distension of the gastric lumen. Treatment should include controlling body temperature, correcting acid/base and electrolyte abnormalities, IV fluid diuresis, oral cold fluids [ice chips] to slow down carbon dioxide production, and possible surgical removal of the dough mass. Blood alcohol levels are run quickly and routinely at most human hospitals and the analysis is also available at many veterinary diagnostic laboratories. In general, the prognosis is favorable.

Several members of the Lilium and Hemerocallis genera can cause a self-limiting gastroenteritis in dogs, but only cats appear to be susceptible to the development of acute renal disease following ingestion. Many lilies are found indoors as potted plants or ornamental displays, and others are used in outdoor flower beds. Easter lily [Lilium longiflorum], tiger lily [L. tigrinum], rubrum lily [L. speciosum], Japanese show lily [L. lancifolium], stargazer lily [L. auratum], some species of the day lily [Hemerocallis], and possibly other members of the lily group have been documented as causing renal disease. All parts of the plant are considered toxic, and the toxic principle(s) have not yet been identified. Aqueous extracts of the leaves and flowers have been shown, experimentally, to be nephrotoxic to cats.

Potency of the toxin may vary between parts of the plant, as well as during different growth stages of the plant; however, based on clinical case reports, it appears that small amounts, as little as a few bites of the leaves, can potentially lead to illness. Within 2 to 12 hours of ingestion, most cats will show vomiting, anorexia, lethargy, hypersalivation and depression. Some of these signs will subside, but then may reoccur with the development of renal disease. Some other initial signs reported include fearful behavior, polyuria, tremors, ataxia and vocalization. Acute renal failure, often oliguric or anuric, will develop 24-96 hours following exposure - signs at this time may include vomiting, depression, dehydration, uremic breath, recumbency, dyspnea, tachypnea, seizures and bradycardia/tachycardia.

Abnormal laboratory findings may include azotemia [creatinine is often extremely elevated], hyperkalemia, hyperphosphatemia, acidosis, isosthenuria, granular casts, glucosuria and proteinuria. Biopsy or postmortem histological assessment of the kidney reveals acute renal tubule degeneration and necrosis, with granular tubular casts [intact basement membrane]. Mineralization may be observed, but usually not to the extent that one sees with EG or vitamin D-type poisonings. Cats that are decontaminated early after exposure [< 6 hours] have a good chance of recovery: emesis / gastric lavage, activated charcoal, cathartic, enemas. These patients should be diuresed and monitored for a minimum of 48 hours before being discharged. The azotemic, anuric cats do not fair so well and most patients respond poorly to the traditional treatments for acute renal failure [IV fluids, furosemide, bicarbonate for the acidosis, potassium supplementation, phosphate-binding agents, nutritional support, etc.]. Long-term, more aggressive forms, of treatment [peritoneal dialysis, hemodialysis, kidney transplant] may be required in order to achieve a successful outcome.

Permethrin toxicosis is well documented in pets, particularly cats. Permethrin, an effective and generally considered safe, insecticide, can be found in spot on formulations, sprays, dips and shampoos. Toxicities in cats have been seen when exposed to recommended dosages, but more commonly when treated with products labeled "to be used on dogs only". Cats can even become clinically ill following exposure to treated dogs. Products containing concentrations greater than 0.20% should not be used on cats. Clinical signs can be immediate or delayed, depending on whether the exposure is dermal, oral or a combination of both. Initial signs often include salivation, vomiting, diarrhea, paw flicking and hyperesthesia. Neurotoxic effects include tremors, and seizures are seen following excessive exposures. Basic decontamination procedures should be instituted for the asymptomatic patient [bathing, emesis, AC and cathartic]. The neurotoxic signs can be controlled with valium or methocarbamol. The patient should be continuously monitored in case either hypo- or hyperthermia develops. Atropine should be avoided.

Lead poisoning in dogs and cats is not as common as it once was, due to decreased use of lead based paint in homes. In actuality, lead is ubiquitous and its sources are many and varied. Cats are commonly exposed to lead through ingestion of dust and chips following home remodeling projects. Common sources of lead for dogs include lead paint chips, old drapery weights, lead sinkers, lead shot, lead solder, old tile-linoleum-roof flashing, and children's toys. Lead shot embedded in muscle tissue does not leach into systemic circulation and therefore poses no problem to the pet. Exposures are almost always oral, and the amount of lead absorbed is dependent on the form of lead and the age of the animal. Younger animals are known to absorb much higher concentrations of lead from the intestine as compared to adults. Once absorbed, lead is bound to erythrocyte membrane proteins and distributed to all tissues. Accumulation tends to occur in the liver, kidney and brain; and long term storage occurs in the bone where it is biologically inert [until calcium is mobilized]. Lead can cross the placenta and endanger the developing fetus, and it can also be secreted into the milk. Absorbed lead is excreted into the bile and urine, particularly following chelation therapy.

One tends to associate lead with neurological signs, but the most common initial clinical signs following ingestion are signs associated with the gastrointestinal system. Within a few days of ingestion [timing is dependent on form of lead], dogs and cats most commonly display mild to moderate, intermittent bouts of abdominal pain, vomiting, depression and anorexia. Later, in the dog, neurological signs may become apparent, with hyperexcitability, hysteria, intermittent seizures and blindness possibly occurring. These neurological changes are rarely observed in cats.

Radiography of the patient can be helpful in identifying possible radioopaque objects within the gastrointestinal tract; however, their absence should not preclude lead testing if the suspicions of lead poisoning are high. The presence of nucleated red blood cells withOUT the presence of an anemia, along with basophilic stippling, can be seen in dogs and cats, but these changes are not pathognomonic and are not present in all cases. The diagnosis of lead is made very easily from testing whole blood [EDTA, heparin] for lead; levels < 0.1 ppm are normal, levels between 0.2-0.5 indicate exposure and may warrant chelation therapy if signs are present, and levels exceeding 0.6 ppm are consistent with a diagnosis of lead intoxication.

The choice of whether or not to treat the lead exposed patient is dependent on the signs observed and the blood lead concentration. The first treatment goal is to identify the source and remove it from both the animal and its environment. Sometimes emetics can be employed to remove small objects within the stomach; however, surgical removal is often used to remove larger and more irregular shaped objects. Magnesium or sodium sulfate cathartics can be given orally to patients ingesting lead paint dust and chips. As these compounds dissociate within the gastrointestinal tract, the lead will bind and precipitate out as lead sulfate that is less readily absorbed and will thereby be excreted out via the feces. Barbiturates or diazepam can be used to control agitation, hysteria and seizures, and vitamin B complex [to provide thiamine] has been shown to be helpful in alleviating some of the neurological signs. Succimer [10 mg/kg BW, PO q 8 hr for 10 days] is an excellent effective chelator to use to enhance lead elimination from the body. Succimer has a good therapeutic index, has few side effects, spares most other elements from being chelated and does not cause enhanced lead uptake from the gut. Blood lead levels should be rechecked a few days following the last dose of succimer; a second round of chelation therapy may be necessary to reduce the lead load. Calcium disodium EDTA [25 mg/kg SQ q 6 hr for 5 days - 10 mg/ml in 5% dextrose - diluting to a 1% solution] can still be used instead of succimer. However, CaEDTA is more expensive, has more side effects, and may cause enhanced lead absorption from the gut. Prognoses are generally favorable for affected patients, though recovery may take a few weeks.

There are many nonsteroidal anti-inflammatory agents, used in both human and veterinary medicine. Ibuprofen, carprofen, deracoxib and naproxen are some of the commonly encountered NSAIDs associated with overexposures. Toxicokinetics and toxicodynamics do vary between drugs, but in general, situations of acute overdosage generally cause similar clinical problems and warrant similar treatment protocols. Exposures can occur through accidental ingestion, inappropriate administration by owners and by malicious means.

NSAIDs can cause gastrointestinal, renal and central nervous system problems. Carprofen exposures > 4 mg/kg in cats and > 20 mg/kg in dogs can cause vomiting, diarrhea, depression, abdominal pain and gi ulceration; > 8 mg/kg in cats and > 40 mg/kg in dogs can cause renal disease. Dosages capable of causing neurological effects [depression, seizures and coma] are unknown. Ibuprofen exposures > 25 mg/kg in cats and > 50 mg/kg in dogs can cause gastrointestinal problems; > 100 mg/kg can result in renal disease; and > 400 mg/kg can cause neurological changes. Naproxen exposures > 10 mg/kg in dogs can cause gastrointestinal problems, and > 50 mg/kg can result in renal disease and neurological changes. Deracoxib exposures > 15 mg/kg in dogs has been associated with gastrointestinal illness; > 30 mg/kg can lead to renal disease. Dosages associated with neurological conditions have not been well defined.

Treatment goals are to prevent further absorption and prevent or correct gastrointestinal, renal and CNS disease. Following acute oral exposures, decontamination procedures should be initiated immediately. These can include emesis, followed by repeated doses of activated charcoal and cathartic. Intravenous fluid diuresis should be started to protect the kidney, at 2-3 times maintenance and continued for a minimum of 72 hours, gradually tapering them down over time. Sucralfate, misoprostol and H2-blockers are used as gi protectants, and are used for 5-7 days or longer. Continuous monitoring of urine output, and repeated blood counts, serum chemistries and urinalyses are performed to determine efficacy of therapy - if changes are observed, treatment is thereby continued and perhaps modified to address the specific changes noted.

Ingestion of coins is surprisingly a not uncommon occurrence in both dogs and cats. Pennies, minted from 1983 on contain approximately 96% zinc [along with some 1982 pennies and Canadian pennies minted from 1997-2001]. Copper is found in the highest concentration in other coins, and does not seem to represent the toxicological hazard as zinc does. The zinc is rapidly leached from the pennies in the acidic environment of the stomach, and systemic levels of zinc can start rising several hours post ingestion. A single penny can pose a risk to an average size dog or cat. Zinc can be found in many other metallic substances.

The initial clinical signs are typically gastrointestinal – vomiting, abdominal pain and diarrhea - then this is followed by general lethargy, inappetance, depression, pale mucous membranes, icterus, which are due to hemolysis. Hypoxia can lead to renal disease and death. Clinical pathological changes may include anemia [regenerative, depending on timing of presentation], hemoglobinemia, hemoglobinuria, bilirubinemia/uria, elevation in liver enzymes, and azotemia. Radiographs can show evidence of a radioopaque substance [may already have passed] and serum levels can be analyzed for zinc [and copper] levels. Electron microscopy can also be used to look for the presence of zinc in metallic objects retrieved from the gastrointestinal tract.

Treatment is symptomatic and supportive in nature. The first objective is to remove the zinc object, followed by IV fluid therapy, blood transfusions and other supportive care. Chelation therapy with CaEDTA or penicillamine can be used, but is generally not necessary because serum zinc levels drop fairly rapidly once the source has been removed from the GIT.

References

Casteel SW. 2006. Lead. In Small Animal Toxicology, Eds. ME Peterson and PA Talcott, Elsevier Inc., pp. 795-805.

Dunayer EK. 2006. New findings on the effects of xylitol ingestion in dogs. Vet Med, Dec. 791-797.

Hall JO. 2006. Lilies. In Small Animal Toxicology, Eds. ME Peterson and PA Talcott, Elsevier Inc., pp. 806-811.

Hansen SR. 2006. Pyrethrins and pyrethroids. In Small Animal Toxicology, Eds. ME Peterson and PA Talcott, Elsevier Inc., pp. 1002-1010.

Magnussen KL. 2003. In a ferment. Veterinary Forum, December 28-30.

Richardson JA. 2006. Ethanol. In Small Animal Toxicology, Eds. ME Peterson and PA Talcott, Elsevier Inc., pp. 698-701.

Talcott PA. 2006. Nonsteroidal antiinflammatories. In Small Animal Toxicology, Eds. ME Peterson and PA Talcott, Elsevier Inc., pp. 902-933.