Ethylene glycol – a common toxicity in cats

Cats can be exposed to many toxic substances – and ethylene glycol (EG) remains one of the most common².

EG – also known as ethanediol – is an odourless liquid that is clear and sweet in taste, making it attractive to animals. It is used in antifreeze solutions in many motorised vehicles, coolants, rust removal solutions, printer ink³, as a preservative for taxidermy⁴ and as a chemical intermediary for some plastics³. The concentration of EG can vary significantly, but can be up to 100% in some products³.

Animals are commonly exposed to EG from vehicles leaking the substance on to the ground, where it can be ingested. Even the smallest spill poses a real threat to small animals, especially cats. Any amount ingested by cats requires immediate treatment. The availability of this substance – along with a low minimum lethal dose and a lack of public knowledge – plays a large role in the frequency of toxicity.

Some products have been replaced with a less toxic formulation, propylene glycol². This is less palatable and converted into lactic acid within the body. Bittering agents may occasionally be used to help deter ingestion³.

EG is not initially toxic, but as it is metabolised by the body, the by-product metabolites cause toxic side effects.

Once a patient has ingested EG, it undergoes rapid gastrointestinal absorption before being metabolised by the liver and excreted renally. Early CNS signs may develop due to the unmetabolised EG³. Toxic metabolites called glycolic acid are formed as a by-product, which cause severe metabolic acidosis, renal and cardiopulmonary signs.

Clinical signs and laboratory changes 30 minutes to 12 hours after exposure include:

• depression
• vomiting
• weakness and ataxia
• tachycardia and tachypnoea
• hypothermia
• polyuria leading to dehydration
• convulsions in severe cases

Laboratory changes include acidaemia, hypocalcaemia may start to develop, electrolyte disturbances, and increased serum osmolality leading to an osmotic diuresis.

Clinical signs and laboratory changes 12 to 24 hours after exposure include:

• hypertension or hypotension
• tachycardia and arrhythmias
• heart failure
• oliguria
• uraemia and/or azotaemia

Laboratory changes include proteinuria, haematuria, glycosuria and albuminuria, and calcium oxalate crystals may be present in the urine. Urine specific gravity (USG) is likely to decrease, but remain above the isosthenuric range. Urinary pH typically remains low (lower than pH6). Hyperglycaemia and ionised hypocalcaemia are seen in more than 50% of cases². Azotaemia and hyperphosphataemia will develop as the acute kidney injury (AKI) progresses². Electrolyte and acid base disturbances are also exacerbated by renal impairment³.

Serum calcium combines with the metabolite oxalic acid, which leads to the formation of calcium oxalate crystals within the vascular system and kidneys². The crystals become deposited in the renal tubules, leading to a life-threatening AKI.

AKI is defined as an abrupt decrease in renal function, which may include both structural and functional damage. Azotaemia occurs due to a decrease in the excretion of nitrogenous waste products (urea, creatinine and phosphate). Electrolyte abnormalities – such as hyperkalaemia and metabolic acidosis – are likely.

AKI is often not a syndrome of one organ, but a systemic illness causing multiple organ dysfunction syndrome.

The three AKI phases to the development of clinical signs⁴ are detailed in Figure 1.

Diagnosis

Diagnosis is very rarely confirmed with laboratory analysis and is based on suspicion of exposure, combined with clinical signs and exclusion of other causes³. Exposure to EG is strongly suggestive if calcium oxalate formation (renal mineralisation and urolithiasis) are present⁵, along with severe metabolic acidosis, decreased urinary output and AKI⁶.

EG test kits can detect blood levels within 30 minutes of ingestion. The kits are also sensitive to propylene glycol and glycerol, which can provide a false-positive result. They carry a relatively high detection limit of greater than 50mg/dl. Cats can be intoxicated with a much lower limit of 20mg/dl – meaning exposed cats can have a negative result⁴.

EG concentrations are only detectable in urine or serum between 48 hours and 72 hours post-ingestion, which is often too late to initiate life-saving therapy⁴.

Fluorescent urine

Fluorescein is often added to EG to help identify radiator leaks. This can often be detected with UV light in the urine of affected animals.

Fluorescein has a half-life of slightly more than four hours and can only be detected in urine with a pH lower than 4.5.

A Wood’s lamp can prove useful to check for fluorescein in the mouth and vomit in the emergency setting.

Some urine collection bags have a fluorescent lining, which could lead to a false-positive result⁷. This technique carries limitations and should not be used as a definitive diagnostic method; however, it can be a useful bedside technique.

Treatment

EG is rapidly absorbed into the gastrointestinal tract; therefore, inducing emesis or nasogastric aspiration should only be considered within one hour of ingestion. It does not readily bind to activated charcoal, so administration is not advised².

A treatment plan should be formed around the prevention of toxic metabolite conversion, reversal of electrolyte and acid base disturbances, and maintaining renal function. IV fluid therapy should be administered along with an antidote. Both ethanol and fomepizole act directly on alcohol dehydrogenase. This prevents metabolisation of toxic metabolites, allowing unmetabolised EG to be excreted renally. Fomepizole is more effective and safer to use than ethanol¹. Fomepizole is very expensive and cats require around six times the dose in comparison to dogs⁸.

Time plays a vital role in the successful treatment of this toxicity and cats must start treatment within three hours of ingestion². Treatment initiated beyond this time is often associated with a mortality rate of almost 100%².

Antidote

• Fomepizole: 125mg/kg slow IV initial dose, then 31.25mg/kg IV at 12 hours, 24 hours and 36 hours post-ingestion^1,2.
• Medical grade ethanol 95% solution: dilute solution to 20% with sterile water for IV administration via a blood filter. Administer 5ml of 20% ethanol solution/kg IV every six hours for five treatments, followed by every eight hours¹ for at least 48 hours.

It is important to administer ethanol for at least 48 hours to block metabolism of EG and allow renal excretion.

Ethanol often causes depression of the CNS and worsening of metabolic acidosis may be seen. Fewer side effects are often associated with fomepizole, and it is deemed a safer and more effective drug.

Other forms of alcohol often contain other substances, making them unsafe for IV administration. The least dangerous type of commercially available alcohol is likely to be vodka, which can be administered orally via a naso-oesophageal feeding tube for clinically mild cases¹. If oral administration is not possible, a solution containing 40% vodka can be administered IV⁸.

Administration of antidote therapy is contraindicated in cats once renal injury is present³.

Haemodialysis

Haemodialysis is available at some hospitals in the UK and may be beneficial for the removal of ethylene glycol and its harmful metabolites². This is often started prior to the onset of an AKI. EG is readily dialysable, although facilities are limited to a small number of veterinary hospitals across the UK.

Nursing care

Nurses are heavily involved in the direct care of the AKI patient in an intensive care setting. The intensity of these cases ideally requires one-to-one nursing care in a 24-hour hospital.

The following requirements are vital for the treatment of AKI:

• Administer antidote therapy urgently, as time plays a vital role in the successful outcome of this toxicity.
• Aggressive fluid therapy should be initiated immediately. High fluid rates are often required to successfully treat AKI. The intravascular volume needs rapid restoration prior to treating dehydration. Isotonic crystalloids are most appropriate and Hartmann’s solution contains buffers to help correct the acidaemia. Sodium chloride should be avoided in acidaemic patients due to its acidic pH. Fluid boluses of 2ml/kg to 10ml/kg should be administered until the patient’s intravascular volume is restored. Administering small boluses with regular monitoring has been shown to have a more successful outcome than administering large shock volumes of fluid therapy, particularly in cats. It is also important to remember that cats may become bradycardic with volume depletion. Provide an appropriate maintenance rate of fluid therapy and replace fluid losses continually⁶.
• An indwelling urinary catheter should be placed with a collection bag to monitor urinary output (Figure 2). The normal urinary output of a cat should be 1ml/kg/hour to 2ml/kg/hour, or 25ml/kg/day to 50ml/kg/day. Oliguria is defined as 0.5ml/kg/hour to 1ml/kg/hour, and anuria lower than 0.3ml/kg/hour.

  

• The patient should be weighed at least twice a day. The patient will gain weight with fluid therapy and should plateau once the fluid volume is stabilised. If the bodyweight decreases, this demonstrates the patient is losing fluid and that fluid therapy should be increased to match the loss. If the patient’s weight is continually increasing beyond its normal, overhydration due to oliguria/anuria is possible and the resting respiratory rate should be closely monitored for evidence of pulmonary oedema.
• USG can provide a useful insight into the kidney’s ability to concentrate urine, although this will be affected by the administration of fluid therapy. Total protein, PCV and blood pressure are tools to help assess fluid volume, and signs of under-infusion or over-infusion⁶.
• Diuresis may be initiated to aid in the excretion of potassium and blood urea nitrogen, while also reducing the risk of overhydration⁶. Administer diuretic therapy and/or vasodilators if urine production is decreasing despite matching ins-and-outs⁶.
• Assess pain score and administer analgesia accordingly. AKI is often painful in the area of the kidneys due to renal dwelling and stretch of the renal capsule.
• Calculate resting energy requirements (RER) and consider placement of a naso-oesophageal feeding tube for the administration of early-onset assisted enteral nutrition. A daily RER of 30 × BW(kg) + 70 can be used accurately in patients between 2kg and 30kg. This can be administered as slow, regular boluses throughout the day or constant rate infusion via a syringe driver.
• In the dull or recumbent patient, it is useful to link up a multiparameter monitor that can be situated outside the kennel. This provides constant visualisation of an ECG to assess for changes in heart rate or rhythm. Oscillometric blood pressure, to monitor for signs of hypotension, and a thermometer can be inserted rectally for continuous monitoring (Figure 3). In the author’s experience, the tail is a useful and well-tolerated location for blood pressure measurements in cats.

  

• Monitor thermoregulation regularly, as cats can become hypothermic very quickly. Take rectal temperature regularly and apply active warming in body temperatures lower than 37°C.

Prognosis

Ethylene glycol toxicity carries a very serious risk to cats. Unless exposure to the toxin was witnessed, cats often present during the later stage of poisoning, which limits treatment options.

According to the Veterinary Poisons Information Service, the overall mortality rate of cats with a confirmed or suspected diagnosis to EG is 85%³. Given that very few cases are confirmed as EG toxicity, it is possible that the recovering cases had only suspected EG exposure.