Heavy metal intoxication in companion animal (Proceedings)

Heavy metals have often been a cause of intoxication in companion animals but the number metals that cause a toxicosis is low. The metal intoxications which might be seen in a clinical practice include arsenic, copper, lead, mercury and zinc. Cadmium is often seen in association with zinc in galvanized metal, but rarely causes an acute problem in animals.

Arsenic, a naturally occurring element, is found throughout the environment; for most people, food is the major source of exposure and is considered a Group A, human carcinogen. Arsenic intoxication, hopefully, is an intoxication of the past as the U.S.E.P.A. has removed approval for most uses of arsenic compounds. However, ashes from arsenic treated wood could be hazardous to pets. The cat is one of the most sensitive animals to arsenic. Clinical signs of oral exposure to arsenic include intense abdominal pain, vomiting, staggering gait, diarrhea, collapse and death.

Death may occur within hours of ingestion under acute to peracute circumstances, but may be delayed for several days. Sub-chronic to chronic exposure of dogs to inorganic arsenicals will induce a dose-dependent weight loss or slower weight gain. It is thought that this is due to lack of appetite and not directly due to the arsenic. The liver and kidney are two of the target organs for inorganic arsenic and there will be noticeable changes in the various clinical pathology measures.

Initial treatment of arsenical ingestions (and all heavy metal intoxications) consists of emptying the stomach by gastric lavage as emesis is contraindicated due to the status of a weaken stomach wall and the likelihood of rupture. Gastric lavage should not be performed if the animal has already vomited. The oral administration of sodium thiosulfate may be beneficial. Dimercaprol (British Anti-Lewisite, BAL) is the chelating agent of choice. BAL is in peanut oil and administered by IM injection at a dose of 2.5 - 5 mg/kg.

The high dose should only be used in acute cases for the first day, only. BAL should be administered every 4 hours for the first  2 days, every 8 hours on the 3rd day and twice a day for the next 10 days. DMSA (Succimer®), an oral chelating agent, is not as effective as BAL in treating arsenic intoxication. Supportive care is very important in all cases of acute heavy metal intoxications.

Acute copper intoxications in dogs and cats is very uncommon and infrequently reported in the open literature as compared to the occurrences in sheep. A swallowed copper-containing item would be the only likelihood and these items might include copper wire, copper jewelry, and possibly old pennies. The occurrence of clinical signs in animals with acute copper poisoning would depend upon the form ingested and if repeatedly ingested. Those signs reported for dogs and cats might include vomiting, depression, diarrhea with mild abdominal pain.

If a soluble form of copper was ingested, animals would exhibit more severe signs than listed previously but would also develop hemolysis leading to hemoglobinuria, hepatocellular necrosis and rapid death. Penicillamine is the chelating agent of choice along with supportive care and fluids. Methyl donors such as S-adenosyl Methionine might be given if signs of liver involvement are detected. The prognosis in these cases would depend upon the degree of GI involvement along with the degree of hemolysis and hepatocellular damage.

Iron is an essential element in mammals and one does not normally think of this element as being toxic. However, iron is one of the leading causes of unintentional intoxications in children under 6 years and potentially a cause of intoxications in pets if allowed access to iron containing preparations. Injectable iron preparations have been involved in iatrogenic intoxications in production animals, but these preparations are not normally given to dogs and cats. Many vitamin preparations for children contain iron and prenatal vitamins for pregnant women often contain more than 60 mg of elemental iron per pill or tablet. Normally no more than 15% of ingested iron is absorbed and only 0.01% of the body burden is excreted, mainly in exfoliated GI mucosa. Since there is no excretory mechanism for iron, the element can build up quite rapidly if an animal is exposed to rather large doses, orally.

Animals ingesting 20 to 60 mg/kg of elemental iron may develop clinical signs. Animals ingesting greater than 60 mg/kg of elemental iron will develop severe clinical signs. Animals ingesting between 100 and 200 mg/kg of elemental iron will probably die. The clinical signs associated with an iron overdosage start with GI upsets and GI bleeding. Depending upon the dose ingested, some animals do not progress beyond this stage. There may be a latent period of apparent recovery of 6 to 24 hours before more severe clinical signs develop and the animals may appear lethargic. These subsequent clinical signs  include a recurrence of the GI signs, metabolic acidosis, hypotension and shock, hepatic necrosis with coagulation defects, cardiovascular collapse and possibly death.

Animals surviving a severe iron intoxication may have strictures due to the healing of ulcers which often occur in the GI tract. Jay Albretsen in Toxicology Brief in Veterinary Medicine, Feb, 2006, has put together a very good algorithm for treating iron intoxication. GI decontamination is a must in the patients along with aggressive supportive  to treat the ensuing shock. Deferoxamine (Desferal®, Novartis), the chelating agent of choice should be given, IM, at dosage rates of 40 mg/kg every 4-8 hours. Deferoxamine can also be given, CRI, at a rate of 15 mg/kg/hr until the serum iron concentrations go below 300 µg/dl or 3 ppm. Depending upon the severity of the intoxication, the prognosis in severely intoxicated animals is guarded to grave.

Lead intoxication in dogs and cats is as important today as it was in times of old. Animals, large or small still find lead containing products to ingest. In today's society, the most common sources of lead are in fishing weights, toys, some jewelry, projectiles and solder. In previous times, lead-based paints, used automotive crankcase oil and even lead glaze on imported pottery (Can still be a problem today). Mature animals absorb only 5-10% of ingested lead, whereas immature animals may absorb 30-40% of ingested lead. Eventually, lead is deposited in bone.

As in the earlier discussed heavy metals, acute lead ingestion will cause acute GI signs. Additionally, lead will induce neurological signs and, and in some cases, hemoglobin deficiencies if the intoxicated animals live for any period of time. The initial clinical signs of lead intoxication is a GI upset with the associated vomiting, diarrhea, and colic followed by either lethargy, hysteria and/or seizures. The therapy for lead intoxicated animals is just like any other heavy metal in that GI decontamination, control of the clinical signs and promoting excretion of the lead must be done.

In many instances, radiographs will demonstrate the presence of a radio-opaque substance in the GI tract or in some other location if it is a projectile. In all cases, blood levels of lead should be determined to allow the clinician to initiate the appropriate therapy. If the opaque material in the GI tract does not appear to be causing an obstruction, then magnesium sulfate should be administered to promote excretion and reduce the solubility of the lead. Otherwise, surgery must be performed to remove the object. If the blood levels of lead are between 0.35 and 1.0 ppm, Succimer® alone at a dosage rate of 10 mg/kg, orally, for 10 days may be adequate. If the blood lead levels are > 1.0 ppm, considerations should be given to administering calcium disodium EDTA and BAL to promote excretion. Some seizures may be controlled with diazepam and thiamine given at doses of 10–20 mg/kg/day has aided in the control of seizures in some animals.

It should be noted that the effects of lead on hemoglobin synthesis can induce an anemia with large numbers nucleated RBCs. Lead projectiles located other than in synovial cavities, may not be problematical, however some humans have developed signs of lead poisoning from projectiles in other anatomic locations. In one study wild fowl, Succimer given at a dosage of 30mg/kg , orally, b.i.d.) for a minimum of 7 days and one IM injection of CaNa2EDTA  at a dosage rate of 25.0 – 50.0 mg/kg, caused an over 90% reduction of blood lead levels.

Zinc is an essential element, but acute zinc poisonings are rather common in dogs, cats and in pet birds exposed to zinc-containing coins and galvanized metal objects such as bolts and nuts, jewelry, toys, and cages. Zinc is readily absorbed via the GI tract and most intoxications occur through the oral route. Dog are more likely to become intoxicated than cats and the most common offending agent is pennies. The mechanism of action of zinc toxicity in not known, but like other heavy metals, is probably binds at -SH groups on certain enzymes to exert its toxic effect.

As with almost all heavy metal intoxications, the initial clinical signs are referable to the GI system with vomiting, abdominal pain and anorexia, distress, and diarrhea.. Melena may or may not be present. Depending upon the amount of zinc ingested, intravascular hemolysis develops in hours to several days. This may be followed by the appearance of either pale or yellow-discolored mucous membranes. The anorexia and other clinical signs may continue.

Following the development of the intravascular hemolysis, hemoglobinuria will develop which could lead to renal disease if not treated aggressively. Radiographic imaging or other imaging technology should be used to ascertain the absence or presence of radio-opaque objects in the GI tract. The absence of these objects does not necessarily rule out zinc toxicosis. Treatment of these cases consists of removing the objects and giving good supportive care. Whole blood should be administered if indicated and the animal should be given adequate fluids to dilute and promote urinary excretion of the hemoglobin.

Diffuse intravascular coagulopathy (DIC) may occur in some animals. Appropriate therapy should be instituted as necessary. Chelation therapy may or may not be required if the object is removed from the GI tract. Calcium disodium EDTA has been the treatment of choice. Penicillamine has also been recommended. Succimer® should be considered, it necessary. The prognosis in these cases depends upon the condition of the animal at the initiation of therapy and whether the offending object is removed from the GI tract.