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Common toxicities in cats (Proceedings)
Decontamination of patients with ingested toxins is achieved by emesis induction or gastric lavage, followed by administration of charcoal (adsorbs toxins enabling their excretion from the GI tract). Cathartics may be added to activated charcoal to hasten elimination.
General decontamination principles
Decontamination of patients with ingested toxins is achieved by emesis induction or gastric lavage, followed by administration of charcoal (adsorbs toxins enabling their excretion from the GI tract). Cathartics may be added to activated charcoal to hasten elimination. Emesis is generally only effective within the first 1 to 2 hours following exposure. Hydrogen peroxide (1-2 ml/kg) is an emetic that is commonly present in households. A commonly used emetic in the cat is xylazine hydrochloride (0.44 to 1.1 mg/kg IM or SC). Potential adverse effects (sedation, bradycardia, arrhythmias, and muscle tremors) can be reversed with yohimbine hydrochloride (0.25 to 0.5 mg/kg IM). Apomorphine hydrochloride does not reliably induce vomiting in cats, and is therefore not recommended in this species.
Acetaminophen is an analgesic, antipyretic that is readily available over the counter and may be inadvertently administered by well-intentioned owners. The drug has an extremely narrow margin of safety in cats and even very small doses can quickly become life-threatening. Toxicity develops at doses above 40 mg/kg, but occasionally as low as 10 mg/kg.
Mechanism of toxicity
Acetaminophen is partly metabolized by microsomal hepatic enzymes. Thereafter, in most species, the majority of the drug undergoes metabolism via two major hepatic conjugation pathways to nontoxic conjugates 1) sulfate and 2) glucuronide. The small remaining portion is metabolized to the toxic NAPQI metabolite, a free radical.
If conjugation pathways are deficient or saturated, metabolism is shifted to alternate pathways and this causes more NAPQI to build up. NAPQI causes lipid peroxidation of cell membranes, cell injury, and cell death. Glutathione can conjugate and neutralize NAPQI.
Cats are deficient in glucuronyl transferase and therefore less able to convert acetaminophen into nontoxic conjugates. Glutathione stores in this species also become easily depleted. With acetaminophen exposure, metabolism leads to an increased accumulation of NAPQI. As glutathione stores are used to conjugate and neutralize NAPQI, these stores quickly become exhausted. Once no additional glutathione is available for binding, unconjugated NAPQI builds up and leads to symptoms of toxicity
Initial symptoms include lethargy, depression, GI signs, tachypnea, and muddy or brown mucous membranes (methemoglobinemia). Facial and paw swelling (vasculitis) finally develop. Hepatic necrosis may occur as well but is less common than in the dog.
With recent exposures, emesis should be induced, followed by activated charcoal. N-acetylcysteine (NAC) is the main antidote. It provides a precursor for glutathione synthesis, can be oxidized to sulfate to participate in the sulfation pathway, and can provide an alternate substrate for conjugation. Replenished glutathione can bind and neutralize any free NAPQI. NAC is administered IV at a dose of 140 mg/kg, followed by subsequent doses at 70 mg/kg q 4-6h for 72 hours. Fluid therapy, supportive care, and GI protectants should be provided. Severe methemoglobinemia may result in dyspnea, requiring oxygen supplementation and transfusions (whole blood or packed cells; improves oxygen carrying capacity).
Vitamin C (30 mg/kg PO or IV q6-8h) may help conversion of methemoglobin to reduced hemoglobin.
Cimetidine (5-10 mg/kg PO or IV q6-8h) can be given to inhibit P-450 liver enzymes, however controlled studies on its efficacy for treatment of acetaminophen toxicosis at this dose are lacking. S-adenosylmethionine (SAMe) is an antioxidant with hepatoprotective properties, and can also be used (180 mg PO, then 90 mg q12-24h; or 30-50 mg/kg q24h).
Prognosis depends on dose ingested, promptness of treatment, and severity of signs at initial presentation. If treatment is implemented within 14 hours of ingestion a better outcome is possible than in cats where it is delayed for 17 hours or longer.
Ethylene glycol (EG) toxicosis
Ethylene glycol is a common toxicant in outdoor cats because of its appealing sweet taste. Ingestion of very small amounts, however, can be lethal. The minimum lethal dose in cats is reported to be 1.5 ml/kg, which is just over a teaspoon in an average sized cat. EG is the main ingredient (95-97%) in antifreeze. Additional ingredients in antifreeze products may include methanol and propylene glycol. High concentrations of EG are also found in many break fluids and in aircraft deicers. Exposure may also occur when pets drink from ‘winterized' toilets in summer homes in northern states. Toxicity occurs most commonly in the fall and winter, when antifreeze use is heaviest. EG ingestion leads to severe metabolic acidosis and acute renal tubular necrosis.
Mechanism of toxicity
EG, a potent alcohol, is quickly absorbed from the GI tract. Food can delay absorption. Half is excreted as unchanged EG by the kidneys. The remainder is metabolized largely by the liver and a small amount by the kidneys. Enzymatic action of alcohol dehydrogenase converts EG into glycoaldehyde and organic acids. Glycoaldehyde is further metabolized to glycolic acid (glycolate), followed by glyoxalate, and then oxalate. Calcium binding with oxalate leads to calcium oxalate crystal deposition throughout the body, particularly the kidneys. The metabolites of EG, particularly glycoaldehyde and glycolic acid, are responsible for the toxicosis. Circulating EG molecules on the other hand act more as a CNS depressant and GI irritant. After ingestion, EG serum concentrations peak by 3 hours, remain elevated for at least 12 hours, but may be undetectable by 48 hours.
Vomiting often occurs shortly after ingestion due to the GI irritative effects of EG. CNS depression can be witnessed within the first 1 to 6 hours first from the depressant effects of alcohol, but the later CNS signs are more influenced by the effects of glycoaldehyde (direct CNS effect, severe metabolic acidosis, hyperosmolality) than EG. Ataxia, depression, inability to stand up, or coma may be seen. Seizures can occur. Polyuria and polydipsia may also be observed during the early phase of toxicity. By 12 to 72 hours, acute renal failure occurs. Urine production progressively declines and is accompanied by a rise in potassium. Fifty percent of patients will develop significant hypocalcemia which can predispose to tetany.
An Ethylene glycol test kit is available (EGT kit, PRN Pharmacal) to look for evidence of EG in the blood and can detect levels of greater than 50 mg/dl. Propylene glycol, which is present in some injectable medications (diazepam, phenobarbital, etc.) and may also be found in activated charcoal, can result in a falsely positive test. Ethanol, methanol, and isopropyl alcohol do not interfere with the test. Toxic EG levels in cats may be below threshold of the test and may result in a falsely negative test. Human hospitals can provide EG concentrations below the EGT kit cut-off, and their quantitative tests are more sensitive for diagnosis in cats.
Induction of emesis and/or gastric lavage can reduce exposure if ingestion was recent (<1-2 hours). It should be avoided in patients showing neurologic signs, since this may predispose to aspiration. The goal of treatment is to block metabolism of EG into its more toxic metabolites. Half-life of EG in the body will as a result increase and treatment will need to continue until all of the EG has been eliminated by the kidneys.
Patients must be treated early and aggressively to assure the best chance at recovery. Aggressive fluid therapy for diuresis and treatment of renal failure should be balanced with risks for volume overload, and diligent monitoring is essential. Treatment of acidosis may be required (bicarbonate). Diazepam or barbiturates can treat seizures but doses must be titrated to avoid worsening CNS depression.
The most important component of treatment are measures to stop the conversion of EG into toxic metabolites, by inhibiting the enzyme alcohol dehydrogenase (ADH). Ethanol, by competing with EG for ADH, can block EG metabolism. Until recently it was the only treatment reported to be successful in the treatment of EG toxicosis in cats. Twenty percent ethanol is administered at 5.0 ml/kg IV q6h for 5 treatments, then q8h for 4 treatments. While inexpensive and readily available, it can worsen acidosis, CNS depression, and osmotic diuresis and intensive monitoring during treatment is therefore crucial.
Fomepizole (4-MP) is an inhibitor of the ADH enzyme. Canine doses are ineffective in cats, and higher doses are required (125 mg/kg, then 31.24 mg/kg at 12, 24, and 36 hours), however CNS side effects are more common. The earlier treatment is implemented, the higher the percentage of unmetabolized EG that can be excreted in the urine. Hemodialysis, when available, can effectively remove both EG and its toxic metabolites from the blood.
Early dx and early aggressive treatment affords the cat the best chance at a successful recovery and survival. When treatment is initiated within 3 hours, prognosis is generally good, although individual variability exists. Patients with oliguria or anuria have a grave prognosis. Survivors may fully recover or have residual renal impairment.
Propylene glycol (PG) is considered less toxic, however may still result in serious toxicosis similar to ethanol, and can also cause anemia in cats. PG is metabolized to lactate and if ingested in toxic quantities can lead to acidosis as well as neurologic signs. Diuresis, treatment of acidosis, and supportive care are standard treatment measures. Ethanol should be avoided (may exacerbate problem), and 4MP has not been evaluated for treatment.
Methanol is most commonly found in “antifreeze” windshield washer fluid and may result in only mild GI upset with small ingestions. Administration of milk and water (for dilution) to exposed cats can reduce nausea. With larger doses (uncommon), significant acidosis can develop.
Many types of lily can cause acute renal failure and death in cats: Easter lilies, Tiger lilies, Daylilies, and Japanese showy lilies. All parts of the plant are considered toxic.
Mechanism of toxicity
Toxicity results in damage to renal tubular epithelial cells leading to renal failure. The exact toxic agent has not yet been identified.
Signs and laboratory findings
Within the first few hours of ingestion, vomiting may occur. Thereafter a period of normalcy or mild depression with decreased appetite may appear. Development of polyuria follows this. Renal failure develops within 12 to 72 hours accompanied by symptoms of uremia. Proteinuria, glucosuria and casts are common and can be seen as early as 24 hours after exposure.
Treatment and prognosis
With known recent exposures, emesis should be induced and activated charcoal along with a cathartic administered. The most effective treatment is early (< 18 hours post exposure) institution of fluid diuresis (2-3 times maintenance) and diuresis must be maintained for at least 24-72 hours (longer if renal failure develops). If implemented before the onset of anuria, this approach leads to survival in most cats. Renal values and electrolytes must still be closely monitored. Progression to oliguria or anuria carries a guarded to poor prognosis, and dialysis may be of benefit in these patients to manage the renal failure while allowing time for tubular regeneration to occur. Delay in treatment can result in irreversible and progressive renal decline and death.
Definition and mechanism of toxicity
Pyrethrins and their synthetic counterparts, pyrethroids, are commonly used insecticides present in flea and tick control products for dogs and cats. Natural pyrethrins are derived from certain species of the chrysanthemum plant. Synthetic pyrethroids have increased environmental stability and are more effective. Common synthetic pyrethroids include permethrin, allethrin, tetramethrin, tralomethrin, and esfenvalerate. Insecticidal activity occurs by binding and opening sodium channels on nerves and causing them to repetitively fire.
Cats are extremely sensitive to permethrin and tolerate only very low concentrations. A common source for toxic exposure is when owners apply dog spot-ons containing high concentrations of permethrin or other pyrethroids to their cat. This can result in rapidly life-threatening toxicosis. Because of their grooming habits, cats may occasionally be exposed through close contact with a recently treated dog.
Signs include twitching, tremors, and seizures. Mydriasis and ptyalism may also be noted. Onset of signs is usually within a few hours, but is occasionally delayed by 24 hours.
Diagnosis is made based on history of exposure and compatible clinical signs. Tissue and blood levels can be checked if confirmation is needed.
Goals of treatment are decontamination, control of tremors and supportive care (IV fluids). Liquid dish washing soap should be used to wash the patient. Avoid hypothermia, which can exacerbate tremors and reduce metabolism of the permethrin. Methocarbamol (50-150 mg/kg slow IV; titrate up as needed) is often very effective at controlling tremors and is the treatment of choice. When IV formulations are unavailable, the oral form can be dissolved in water and given rectally. Diazepam, barbiturates, or inhalant anesthesia may be necessary to control seizures. Diazepam has poor tremor control.
Most cats with appropriate supportive care and treatment have a good outcome and are often well enough to be discharged within 24 to 96 hours of admission. Prolonged seizures can precipitate cerebral edema and DIC and prognosis in these cats is guarded.
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