Birgit Puschner, Julie E. Dechant
Common Toxins in Equine Practice
Birgit Puschner, Julie E. Dechant
Intoxications in horses are infrequent but can result in acute and often lethal presentations or chronic illness. Although acutely poisoned horses require immediate attention, they are more likely to receive targeted treatment because the likelihood for reaching a confirmed diagnosis is greater with acute poisoning. In contrast, chronic poisonings are difficult to diagnose because exposure to a toxicant may have occurred weeks to months before clinical signs become noticeable, and a plausible connection to a toxicant cannot always be made.
Intoxications should be suspected if multiple animals are affected or there are unusual clinical signs or unexplained deaths. Animals newly introduced to the property, poor quality or inadequate feed, change in management or feeding routine, feeding a new feed or new batch of feed, administration of medications, and recent wind storms may all be associated with toxicity presentations. Plant-associated or environmental toxicants can have regional distributions, and it is important for veterinarians to be familiar with toxicants common to their area. Veterinarians should consult or work with a toxicologist when undertaking a diagnostic workup of a case suspected of involving a toxic etiology (Box 211-1). Some intoxications may be multifactorial, such as ivermectin toxicosis and poor body condition or concurrent exposure to Solanum plant species. Recently, intoxications associated with formulation errors in compounded medications have caused morbidity and death in multiple animals in well-publicized events. Collection technique for various types of specimens, sample handling, shipping, and other particulars involved in routine toxicologic testing are summarized (Box 211-2).
Ingestions of oleander (Nerium oleander), a drought-resistant plant cultivated widely in the southern and western United States, causes one of the most commonly diagnosed plant poisonings in horses in that region. Consumption of 5 to 10 oleander leaves can cause clinical signs that lead to death within hours. The entire fresh or dried plant, including seeds, fruit, and root, is toxic because of the content of cardiac glycosides. Cardiotoxicity is primarily a result of Na+/K+-ATPase inhibition, which effectively increases intracellular calcium concentrations and triggers spontaneous depolarizations.
Horses may develop colic, weakness, tremors, anorexia, excessive salivation, dyspnea, cardiac arrhythmias, and death after exposure. Cardiac abnormalities include bradycardia, tachycardia, atrioventricular block, weak pulses, ectopic beats, and gallop rhythms. Sublethal exposure may result in nonspecific clinical signs, followed by renal failure. The mechanism for renal injury is unknown, but inhibition of renal tubule Na+/K+-ATPase may be directly nephrotoxic, or decreased renal blood flow subsequent to hypovolemia may cause renal failure.
In acute oleander toxicosis, serum chemistry changes are limited. Myocardial damage can lead to hyperkalemia, high serum values for creatine kinase (CK) and aspartate aminotransferase, and high serum cardiac troponin I concentration. Horses with renal injury will be azotemic. Postmortem lesions may include endocardial or epicardial hemorrhages and multifocal myocardial degeneration and necrosis.
Oleander poisoning in live animals is confirmed by detection of oleandrin in serum, urine, or gastrointestinal contents, with serum being the sample of choice. In a deceased animal, gastrointestinal contents, liver, and heart tissue can be analyzed for oleandrin. Visual and microscopic examination of stomach or intestinal contents for plant fragments can aid in the diagnosis.
There is no approved antidote for cardiac glycoside intoxication in horses. Digoxin-specific Fab antibody fragments cross-react with cardiac glycosides in oleander but have not been studied in horses and are likely cost prohibitive for most owners. Treatment should be initiated promptly, but may not alter the clinical course in lethal intoxications. Activated charcoal (1 to 2 g/kg, given with water by nasogastric tube) should be administered repeatedly over several days to prevent continued absorption through enterohepatic circulation of the toxins. Supportive treatment should include intravenous fluid administration (preferentially calcium-free polyionic fluids) and antiarrhythmic drugs. It is important to regularly evaluate serum K+ concentrations for hyperkalemia.
Preventing oleander exposure is the most successful control strategy. It is important to educate horse owners about poisonous plants, especially how to recognize oleander and how to safely remove it from pasture and hay. Owners should know about resources for determining which toxic plants are found in their region and where to submit plant samples for identification.
Ionophores constitute a heterogeneous group of antimicrobials that enhance ion permeability across cell membranes. Ionophores, such as monensin, salinomycin, narasin, lasalocid, maduramicin, and laidlomycin, are used extensively in ruminants and poultry as coccidiostats and growth promoters. Exposure or consumption of ionophores in nontarget species (including humans, horses, dogs, and cats) or excessive exposure in target species can result in poisoning. Most reports of ionophore poisonings in horses are a result of exposure to salinomycin, monensin, and lasalocid, with reported LD50 values in horses of 0.6, 2 to 3, and 15 to 21.5 mg/kg, respectively, illustrating that horses are uniquely sensitive to ionophore toxicosis. Monensin and salinomycin are monovalent ionophores with higher affinities for Na+ than K+, whereas lasalocid is a divalent ionophore that binds to Ca2+ and Mg2+. After ionophores bind to their respective cations, transmembrane ion gradients and electrical potentials required for normal cell function are disrupted. Mechanisms leading to cell death include adenosine triphosphate depletion, increased Ca2+ influx, and mitochondrial damage and decreased cellular energy production. Excitable cells in nervous, cardiac, and musculoskeletal tissues are particularly sensitive to the toxic effects of ionophores.
The clinical manifestation of ionophore toxicosis in horses depends on the dose ingested. In extremely large exposures, horses can die within minutes. Typically, poisoned horses develop clinical signs within 12 hours of exposure, manifesting as inappetence, lethargy, profuse sweating (specifically with monensin), colic, restlessness, paresis, recumbency, respiratory distress, and myoglobinuria. Atrial fibrillation, atrial and ventricular extrasystoles, and intraventricular block have been reported, and horses surviving acute ionophore toxicosis are at risk for developing cardiac abnormalities. Chronic heart failure and neurologic impairment are possible long-term consequences of ionophore intoxication, developing several weeks to months after exposure.
Common serum chemistry findings include high CK, aspartate aminotransferase, and alkaline phosphatase values. Increased plasma cardiac troponin I concentrations can be detected with myocardial damage, and values may be high in surviving horses for months after exposure. Electrolyte abnormalities include hypokalemia, hypocalcemia, and hypomagnesemia. Myoglobinuria has been detected in ionophore-poisoned horses, pigs, and humans. Cardiac examination may reveal ventricular dysrhythmias, pericardial fluid, altered contractility, and premature depolarizations. Horses dying from ionophore poisoning may have epicardial hemorrhages, myocardial degeneration, and degeneration of skeletal muscles; however, lesions may be absent or minimal in peracute cases.
Testing for ionophores is necessary to confirm a diagnosis. In live horses, serum or stomach contents can be analyzed for ionophores. Serum is positive for monensin at least 48 hours after exposure in horses. In deceased animals, stomach contents and liver and heart tissue can be analyzed for ionophores. Feed analysis is critical to identifying the source and concentration of the ionophore.
There is no antidote or specific treatment for ionophore poisoning. If exposure is suspected, early decontamination and vigorous supportive care are critical. Administration of activated charcoal (1 to 2 g/kg) may reduce the quantity of ionophore absorbed from the gastrointestinal tract following recent exposure. Removal of the suspect feed or source of ionophore is important. Fluid therapy may help correct electrolyte abnormalities. Administration of vitamin E (1500 to 2000 IU, PO, every 24 hours) and selenium (e.g., sodium selenite, 5.5 mg/450 kg, IM), which stabilize cell membranes and prevent lipid peroxidation, is recommended. Cardiac abnormalities must be treated as indicated. Long-term clinical signs (cardiomyopathy and neurologic impairments) must be evaluated in survivors. Some horses return to their previous activity level.