Canine and Feline Epilepsy. Luisa De Risio
colonic lavage in symptomatic animals, administration of activated charcoal with a cathartic) (Table 4.1), methocarbamol or diazepam in animals with excessive tremors (Table 4.1), AEMs (see Table 4.1 and Chapters 12 and 24) in seizuring animals, symptomatic and supportive care. Calcium gluconate (see hypocalcaemia) should be administered if serum-ionized calcium concentration is equal or lower than 0.8 mmol/l (3.2 mg/dl). In addition, administration of sodium bicarbonate or acetamide has shown promising results (O’Hagan, 2004; Parton, 2006). The recommended dosage of sodium bicarbonate is 300 mg/kg (3.6 ml/kg of 8.4% solution) IV over 15–30 min. Alternatively, half of the calculated dose may be given as a bolus and the remainder infused slowly. Administration of sodium bicarbonate may worsen hypocalcaemia and cause hypokalaemia and hyper-natraemia. Serum-ionized calcium, sodium and potassium levels should be monitored regularly in order to implement fluid therapy as well as calcium and potassium supplementations as required.
The recommended dosage of acetamide (15 g of acetamide granules dissolved in 1 l of warmed 5% dextrose) in dogs is 10 to 25 ml/kg IV (infused though a filter following sterilization) over a 60-min period followed by approximately 5 ml/kg/h IV for the next 12 to 18 h until resolution of clinical signs. In cats with fluoroacetate poisoning, the acetamide dose should be reduced by at least 75% (Parton, 2006). Electrolytes should be closely monitored as hyponatraemia may develop due to the large volume of administered free water.
Other treatment modalities are being investigated in Australia and New Zealand due to the higher prevalence of sodium monofluoroacetate poisoning than other countries.
Prognosis
The prognosis is poor to grave, depending on the amount of sodium monofluoroacetate ingested and the severity of clinical signs at initial evaluation (Goh et al., 2005). Early acetamide or sodium bicarbonate treatment and good supportive care can improve survival (O’Hagan, 2004; Parton, 2006).
Automotive Products
Ethylene glycol
Overview
Ethylene glycol is a commercial antifreeze automotive product whose metabolites, including glycolic acid, are extremely toxic to dogs and cats. Common sources of exposure include container spill, engine flush or engine leak (Khan et al., 1999). Intoxication is most commonly accidental but can also be malicious.
Mechanism of action
Ethylene glycol is biotransformed to glycolic acid, which is metabolized to formic acid, oxalic acid and oxalate. These metabolites are highly toxic and result in severe metabolic acidosis and acute renal failure. The oxalate combines with calcium to form oxalate crystals in renal tubules (especially proximal), urine and within the lumen or perivascular space of cerebral capillaries (Dial et al., 1994a).
Hypocalcaemia secondary to calcium oxalate deposition may contribute to CNS signs, although the concurrent metabolic acidosis shifts calcium to the ionized active state, reducing the chances of hypocalcaemia-associated clinical signs. Acidosis may also contribute to cerebral damage.
Clinical presentation
Clinical signs usually occur within 30 to 60 min of exposure and include obtundation, vomiting, ataxia, seizures, hypothermia, severe metabolic acidosis, serum hyperosmolality, polydipsia, polyuria, calcium oxalate monohydrate and dihydrate crystalluria, isosthenuria and eventually renal failure (Dial et al., 1994a).
Diagnosis
Ethylene glycol colorimetric spot tests are available for use with urine and serum. However, these tests can give false negatives in cats as the ethylene glycol toxic dose in cats can be below the detectable level of the ethylene glycol test kit. False positive results can occur in animals administered medications containing propylene glycol (diazepam, activated charcoal). A quantitative test kit has recently been evaluated and may aid in timely diagnosis of ethylene glycol exposure (Scherk et al., 2013). Laboratory tests for rapid analysis of serum, plasma or urine for ethylene glycol and glycolic acid also have been reported (Smith and Lang, 2000; Van Hee et al., 2004). Birefringent crystals may be detected in urine 3 h (in cats) and 5 h (in dogs) after ingestion. Anion gaps greater than 40–50 mEq/l are also suggestive of ethylene glycol intoxication. Signs of acute renal failure (azotaemia, hyperkalaemia, hyperphosphataemia) are usually seen approximately 12–48 h post-ethylene glycol ingestion. Moderate to severe hypocalcaemia is frequently present. Serum osmolality as high as 450 mosm/kg serum and an osmole gap as high as 150 mosm/kg serum may be detected 3 h after ethylene glycol ingestion. Both the gap and the measured osmolality may remain elevated for approximately 18 h after ingestion. Ultrasonographic changes vary from mild to marked increases in renal cortical echogenicity. Another diagnostic procedure that may help in the early diagnosis of ethylene glycol intoxication is examination of the oral cavity, face, paws, vomitus and urine with a Wood’s lamp to determine whether they appear fluorescent. Many antifreeze solutions contain sodium fluorescein, a fluorescent dye that aids in the detection of leaks in vehicle coolant systems (Thrall et al., 2006).
Management
Treatment should be instituted promptly even if the results of confirmatory tests are not available yet. Treatment is aimed at preventing absorption, increasing excretion and preventing metabolism of ethylene glycol using a chemical antidote such as fomepizole or ethanol. Although therapeutic recommendations have traditionally included induction of vomiting, gastric lavage and administration of activated charcoal, it is likely that these procedures are not beneficial because of the rapidity of ethylene glycol absorption (Thrall et al., 2006). In addition, absorption of ethanol is inhibited by charcoal. Fomepizole (4-methylpyrazole), a competitive inhibitor of alcohol dehydrogenase, is considered safe and effective for dogs if started within 8 h of exposure (Table 4.2) (Dial et al., 1994a; Connally et al., 1996). Fomepizole can be used also in cats, although a much higher dosage is required (Dial et al., 1994b). If Fomepizole is not available, 20% ethanol can be used (Table 4.2). It acts as a competitive substrate for the enzyme alcohol dehydrogenase. Although effective in the treatment of ethylene glycol toxicity, ethanol may result in CNS and respiratory depression. Supportive and symptomatic care includes intravenous fluids to correct dehydration, acid-base and electrolyte imbalances and to promote diuresis, and AEMs in seizuring animals (see Table 4.1 and Chapters 12 and 24).
Prognosis
The mortality rate in dogs is reported to range from 59% to 70% and is thought to be even higher in cats. However, prognosis has been reported to be favourable in dogs and cats treated within 8 and 3 h following ingestion, respectively (Thrall et al., 2006).
Table 4.2. Fomepizole and ethanol dosage in the treatment of ethylene glycol toxicity.
| Medication | Species | Dosage |
| Fomepizole | Dog | 20 mg/kg IV initially as a loading dose, followed by 15 mg/kg IV at 12 and 24 h, and 5 mg/kg IV at 36 h |
| Fomepizole | Cat | 125 mg/kg IV initially, followed by 31.25 mg/kg IV 12, 24 and 36 h after the initial bolus |
| 20% ethanol | Dog | 5.5 ml/kg of a |