Diagnosis and management for veterinary surgeons
Anti-freeze products contain ethylene glycol (EG) and are used in car radiators and occasionally brake and transmission fluid.
Cats are susceptible to ethylene glycol toxicity with a minimum toxic dose of just 1.4 ml/kg. Exposure occurs when cats drink the toxin (it is sweet-tasting) or when anti-freeze is added to water sources or their coats/feet are contaminated with the chemical. Malicious poisoning has been suspected in some cases.
The toxic products of the metabolism of ethylene glycol cause metabolic acidosis and renal tubular damage resulting in acute renal failure (ARF). EG is metabolised by the enzyme alcohol dehydrogenase (AD) to glycoaldehyde and further metabolised to acidic products and oxalate. Formation of calcium oxalate crystals occurs resulting in hypocalcaemia and crystalluria.
Initial clinical signs ( less than 12 hours post intoxication) are gastrointestinal (vomiting) and neurological (ataxia, depression, ‘drunken’ appearance) representing intoxication due to the EG and glycoaldehyde.
12 to 24 hours after EG ingestion further depression is observed along with anorexia, tachycardia and the start of ARF.
After 24 hours clinical signs reflect ARF and include oliguria or anuria and vomiting. If the cat is hyperkalaemic bradycardia may be noted. Unfortunately it is unusual to identify a cat in the earlier stages and most have ARF at presentation. With ingestion of large volumes of EG severe signs including ARF can occur sooner ( less than 12 hours).
Diagnosis is usually based on clinical/clinicopathological findings as cats are rarely observed ingesting EG. Azotaemia is present if ARF has developed, along with hyperphosphataemia. Hypocalcaemia (total and ionised) may be noted. Hyperkalaemia may be present with oliguric or anuric renal failure. An increased anion gap acidosis is commonly observed. Urinalysis will reveal isosthenuria and calcium oxalate monohydrate crystals, which vary in appearance from rounded to more pointed (see figure). Renal ultrasound may demonstrate hyperechoic cortices. The bladder may be small, reflecting reduced urine production. Ethylene glycol blood levels are rarely measured due to the delay receiving results and low toxic dose in cats.
If cats are observed ingesting EG and examined rapidly ( less than one hour) then gastric decontamination with induction of emesis can be attempted. This is contraindicated if consciousness is reduced due to the risk of aspiration. Metabolism of EG can be inhibited by ethanol, which acts as a preferred substrate for AD.
After 12 hours or once ARF has developed treatment with ethanol is unlikely to be effective and may complicate management of ARF. However, prior to the development of ARF then 20% medical ethanol can be administered IV at a dose of 5 ml/kg intravenously over 15 minutes and repeated every 6 hours for five treatments then every 8 hours for four treatments.
In an emergency, if medical ethanol is not available, plain vodka has been used, calculating the dose based on the alcohol content of the preparation. Alternatively a constant rate infusion of 1.25 ml/hr can be used for up to 72 hours to ensure EG elimination. Oral administration of other alcohol products (eg, vodka) is described but associated with severe gastrointestinal irritation and the risk of vomiting and aspiration in depressed patients. If used, patients should be constantly monitored for respiratory and central nervous system deterioration and electrolytes monitored regularly.
Management of ARF should focus on the following:-
Correction of fluid deficits and ongoing fluid therapy
Most cats will be hypovolaemic on presentation and intravenous bolus crystalloids (0.9% NaCl if hyperkalaemic) should be given to restore renal perfusion. Bolus doses of 10-20 ml/kg given over 20 minutes followed by re-assessment should be repeated until deficits are corrected. Monitor urine production (see below) and match to infusion rates adding ongoing losses due to vomiting, and maintenance requirements. Volume overload is a risk and indicated by weight gain, tachypnoea, chemosis and crackles on thoracic auscultation. Cats should be re-assessed by clinical examination every 30 minutes during initial treatment. If available, arterial blood pressure should be monitored and fluid therapy used to maintain systolic pressure of at least 100mmHg. Ideally a central venous catheter should be placed to help ensure adequate but not excessive fluid therapy is being provided.
Restoration of urine output
Ideally place a urinary catheter to measure output and as a minimum the bladder should be palpated every 30 to 60 minutes. Urine output should be maintained at greater than 0.5 ml/kg/hr and correction of hypovolaemia alone may restore urine production. A fluid ‘challenge’ may be used (ie, 10 ml/kg over 20 minutes after correction of volume deficits) with close monitoring for hypervolaemia. Diuretics should not be used until volume deficits are corrected. If the cat remains olig/anuric then administer furosemide (2 mg/kg intravenously) repeated after 30 to 60 minutes if oliguria persists. Mannitol (an osmotic diuretic) should be used with caution as cats with EG toxicity are often hyperosmolar and overhydration may occur. A polyuric phase may occur following restoration of urine output and fluid therapy should be adjusted to meet such losses.
Correction of acid-base and electrolyte abnormalities
Severe hyperkalaemia will result in cardiac arrhythmias and ECG abnormalities (bradycardia, spiked T wave). Correction of fluid deficit and restoration of urine production may correct the hyperkalaemia. If persistent or marked ECG abnormalities then intravenous calcium gluconate may be given whilst monitoring the ECG (cardioprotective only, no effect on potassium level). Intravenous glucose will stimulate endogenous insulin production and reduce hyperkalaemia. Insulin treatment with glucose supplementation should be reserved for severe, refractory cases as hypoglycaemia can occur. If the cat is severely acidotic then sodium bicarbonate may be given but overcorrection may occur without close monitoring and accurate fluid therapy is more important; sodium bicarbonate administration may also worsen hypocalcaemia. Sodium bicarbonate should not be used if blood pH cannot be measured. Hypokalaemia may occur after correction of hyperkalaemia and may require supplementation during the polyuric phase.
Additional treatment including antiemetics and gastro-protectants may be required.
Peritoneal dialysis may be indicated if azotaemia fails to improve and is available at some referral centres.
Unfortunately the prognosis is poor for cats with ARF but recovery can occur with early aggressive treatment. Reporting of cases to the Veterinary Poisons Information Service (VPIS; tel: 020 7188 0200) is advised.