Ethylene Glycol Toxicity

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Introduction

Ethylene Glycol is a sweet tasting fluid that is the main constituent of anti-freeze products.[1]. Consequently in northern hemishpere ethylene glycol toxicity is frequently encountered in practice. It has a relatively low minimum lethal dose, and its sweet, palatable taste makes it attractive to dogs, cats and other small animals, although any animal is susceptible to ethylene glycol toxicosis. [1], [2],[1]. The minimum lethal doses for dogs, cats, cattle and poulty are, respectively 6.6ml per kg body weight, 1.4ml per kg body weight, 2-10ml per kg body weight and 7-8ml per kg body weight [1], [1].



Signalment

  • Dogs: all ages, both sexes, following intoxication lower incidence of fatalities in dogs compared to cats [3]
  • Cats: all ages, both sexes
  • Birds:
  • Other: including pigs and cattle [3]

Diagnosis

Clinical Signs

Severity of clinicals signs is inversely proportional to amount ingested. Time post-ingestion is also important.[1].

  • Dogs: Ataxia, mild to severe increasing depression and other neurological signs, tachycardia, tachypnoea, polydypsia, polyuria, dehydration, anorexia, emesis, miosis, hypothermia
    • if untreated coma and death, or if lesser amount ingested oliguric acute renal failure within 2 to 7 days after ingestion .[1], [3].
      • if untreated anuric acute renal failure
  • Cats: Ataxia, pronounced depression and other neurological signs, tachycardia, tachypnoea, polyuria, dehydration, anorexia, emesis, miosis [3], [3].
    • coma and death if untreated, or if lesser amount ingested oliguric acute renal failure within 1 day after ingestion
      • if untreated anuric acute renal failure

Laboratory Tests

  • Blood:Metabolic Acidosis, increased serum osmolality, increased anion gap, decreased plasma bicarbonate concentration, decreased PCO2, decreased, blood pH, ethylene glycol (in-house colorimetric kit) [1], although concurrent use of drugs such as diazepam and etomidate both of which contain propylene glycol can confound results Cite error: Closing </ref> missing for <ref> tag, and hypocalcaemia as a consequence of this[1] and also as a consequence of ionised calcium binding to ethylene glycol metabolites.
  • Urine:increased urea and creatinine, hyperkalaemia, calcium oxalate crystalluria [1], ethylene glycol (in-house colorimteric kit)[1].

Ultrasonography

  • Renal accumulation of calcium oxalate crystals results in hyperechogenicity upon ultrasound examination [4].

Biopsy

  • Needle or surgical wedge biopsy of kidney [5].

Pathology

Ethylene glycol toxicosis usually results from ingestion although there have been reports of skin contamination resulting in toxicosis in cats [1]. It is absorbed relatively quickly from the gastrointestinal tract [1], hence the quick manifestation of clinical signs following intoxication. After absorption transformation to its more toxic metabolites takes place in the liver and kidney [1]. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body [1] . The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole [3] , is responsible for the initial conversion of ethylene glycol to glycoaldehyde [1]. Glycoaldehyde in turn is metabolised to glycolic acid. Following this glycolic acid is converted to glyoxylic acid. This reaction, along with the earlier conversion of ethylene glycol to glycoaldehyde, are the rate-limiting steps in the metabolism of ethylene glycol. Finally glycolic acid undergoes metabolic transformation to produce the end product, oxalic acid. Glycolic acid and oxalate are directly nephrotoxic, leading to necrosis of the renal tubules. Glycolic acid is the main metabolite reposponsible for the metabolic acidosis, although oxalate contributes, as does lactic acid, whose formation is increased as an indirect result of the metabolic pathway outlined above [1] . The metabolic acidosis interferes with normal metabolic pathways [1]. In addition to being directly nephrotoxic oxalate binds ionised calcium in the serum forming calcium oxalate crystals which are excreted by the kidney [1]. . Some of these crystals accumulate within the kidney tubules resulting in further nephrotoxicity and decreased or complete prevention of urine production. The hypocalcaemia that is present is due not only to calcium oxalate crystal formation but also to the hyperphosphataemia that results from the acute renal failure. The decreased serum calcium level leads tetany [1].


Treatment

  • Prevent further absorption of Ethylene Glycol: only beneficial if animal presents one to two hours post ingestion
    • Administration of an Emetic eg syrup of ipecachuanha, apomorphine, sodium carbonate crystals [1].
    • Gastric Lavage
    • Administration of Adsorbents eg activated charcoal [1], [1].


  • Specific Antidotes that Prevent Metabolism of Ethylene Glycol benefits dependent of time post ingestion, see prognosis
    • Ethanol: useful in both dogs and cats [1] ethanol acts as an antidote by competitively inhibiting alcohol dehydrogenase [1]. Recommended intravenous dose for cats is 5ml of 20% ethanol solution per kg body weight every 6 hours for the first 30 hours and then every 8 hours for the next 32 hours [1].
    • 4-Methyl Pyrazole: Fomepizole Initially thought to be effective in dogs only but if given at a higher dose can be effective in cats also [1]. Its advantage over ethanol is that it has less side effects and is the treatment of choice in dogs [1] . It acts by directly inactivating the enzyme alcohol dehydrogenase [1]. Recommended doses for dogs are 20mg per kg of a 50mg/ml solution (intravenous) followed by 15mg per kg (intravenous) 12 hours and 24 hours later and a final dose of 5mg per kg 36 hours later [1]. Cats require a dose of 125mg per kg body weight to be administered intravenously every hour for three hours post ingestion, followed by a lower intravenous dose of 31.25mg per kg body weight at twelve hour intervals post-ingestion untill 36 hours have passed.
  • Promote excretion of Ethylene Glycol
    • Fluid Therapy promotes diureses and helps prevent dehydration [1]. Also useful in acute renal failure.
    • Sodium Bicarbonate: Ethylene Glycol is a weak acid. Therefore in order to increase the rate of renal clearance sodium bicarbonate can be administered to dogs. Intravenous administration of sodium bicarbonate at a concentration of 1-2 mmol/kg every 3 to 6 hours achieves sufficient alkalinisation of the urine.[6]. Also useful in management of metabolic acidosis see below
  • Management of Metabolic Acidosis
  • Management of Acute Renal Failure
    • Attempt to re-establish normal fluid and electrolyte balance

Prognosis

Prognosis is dependent on how soon treatment with an antidote commences following intoxication. If cats are administered an antidote within three hours of ingestion, and dogs within five hours then the prognosis is good. Treatment is still extremely beneficial in dogs up to eight hours post ingestion, and is worth commencing up to thirty six hours postingestion [1] .

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 The 5-Minute Veterinary Consult, Canine and Feline, Lippencott, Williams and Wilkins Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiples" defined multiple times with different content
  2. ↑ Feline Medicine and Therapeutics
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 The 5-Minute Veterinary Consult, Canine and Feline (Second Edition),Lippencott, Williams and Wilkins Cite error: Invalid <ref> tag; name "multiple" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiple" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiple" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiple" defined multiple times with different content Cite error: Invalid <ref> tag; name "multiple" defined multiple times with different content
  4. ↑ Textbook of Veterinary Internal Medicine, (Seventh Edition), Ettinger and Feldman; p1968
  5. ↑ Textbook of Veterinary Internal Medicine, (Seventh Edition), Ettinger and Feldman; p1968
  6. ↑ Canine Medicine and Therapeutics (Fourth Edition, 1998),Blackwell Science, p1049
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