Difference between revisions of "Ethylene Glycol Toxicity"

Revision as of 19:48, 17 November 2010

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. ^[1], ^[2],^[3]

Signalment

Dogs: all ages, both sexes, following intoxication lower incidence of fatalities in dogs compared to cats ^[1]
Cats: all ages, both sexes
Birds
Other including pigs and cattle ^[1]

Diagnosis

Clinical Signs

Severity of clinicals signs is inversely proportional to amount ingested. Time post-ingestion is also important.^[3].

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 .^[3], ^[1].
  - if untreated anuric acute renal failure
Cats: Ataxia, pronounced depression and other neurological signs, tachycardia, tachypnoea, polyuria, dehydration, anorexia, emesis, miosis ^[1],

^[1].

- 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

Metabolic Acidosis, increased serum osmolality, increased anion gap, decreased plasma bicarbonate concentration, decreased PCO2, decrease blood pH
increased urea and creatinine, hyperkalaemia,
Hyperphosphataemia due to acute renal failure ^[3].
- Hypocalcaemia as a consequence of this^[3].

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 ^[3]. It is absorbed relatively quickly from the gastrointestinal tract, hence the quick manifestation of clinical signs following intoxication. Following absorption transformation to its more toxic metabolites takes place in the liver and kidney. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body. The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole, is responsible for the initial conversion of ethylene glycol to glycoaldehyde. This reaction, along with the later conversion of glycolic acid to glyoxylic acid, are the rate-limiting steps in the metabolism of ethylene glycol. Glycolic acid is one such metabolite. It is a direct metabolite of glycoaldehyde which itself is produced following the actions of the enzyme alcohol dehydrogenase on ethylene glycol.

Tetany results from the binding of Ethylene Glycol meatabolites to calcium ions present in serum ^[3].

Treatment

Ethanol: useful in both dogs and cats ^[3].

4-methylpyrazole:Dogs only mode of action is to inhibit ADH in the liver. Recommended doses 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 ^[3].

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]

Prognosis

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 The 5-Minute Veterinary Consult, Canine and Feline, 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 Cite error: Invalid <ref> tag; name "multiple" defined multiple times with different content
↑ Feline Medicine and Therapeutics
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 ^3.8 http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 31.10.2010 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
↑ Textbook of Veterinary Internal Medicine, (Seventh Edition), Ettinger and Feldman; p1968
↑ Textbook of Veterinary Internal Medicine, (Seventh Edition), Ettinger and Feldman; p1968
↑ Canine Medicine and Therapeutics (Fourth Edition, 1998),Blackwell Science, p1049

[multiple-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 The 5-Minute Veterinary Consult, Canine and Feline, 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 Cite error: Invalid <ref> tag; name "multiple" defined multiple times with different content

[2] Feline Medicine and Therapeutics

[multiples-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 ^3.8 http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 31.10.2010 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

[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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[2]

[3]

[4]

[6]

@@ Line 1: / Line 1: @@
-{{OpenPagesTop}}
+{{unfinished}}
 ==Introduction==
-Ethylene Glycol is a sweet tasting fluid that is the main constituent of anti-freeze products.<ref name="5-Minute">Tilley and Smith (2000) '''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition), ''Lippencott, Williams and Wilkins''</ref>. Consequently in northern hemisphere 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. <ref name="5-Minute" /><ref name="Merck online">[http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm Merck Veterinary Manual, accessed online on 31.10.2010]</ref><ref name="Gorman" />. The minimum lethal doses for dogs, cats, cattle and poultry 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. <ref name="5-Minute" /><ref name="Merck online" />
+Ethylene Glycol is a sweet tasting fluid that is the main constituent of anti-freeze products.<ref name="multiple">'''The 5-Minute Veterinary Consult, Canine and Feline''', ''Lippencott, Williams and Wilkins''</ref>. 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. <ref name="multiple">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref>,    <ref>'''Feline Medicine and Therapeutics'''</ref>,<ref name="multiples">http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 31.10.2010 </ref>
 ==Signalment==
-*'''Dogs:''' all ages, both sexes, following intoxication lower incidence of fatalities in dogs compared to cats <ref name="5-Minute" />
+*'''Dogs:''' all ages, both sexes, following intoxication lower incidence of fatalities in dogs compared to cats <ref name="multiple">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref>
 *'''Cats:''' all ages, both sexes
 *'''Birds'''
-*'''Other:''' including pigs and cattle <ref name="Merck online" />
+*'''Other''' including pigs and cattle <ref name="multiple">http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 31.10.2010 </ref>
 ==Diagnosis==
 ===Clinical Signs===
-Severity of clinical signs is inversely proportional to amount ingested. Time post-ingestion is also important.<ref name="Merck online" />
+Severity of clinicals signs is inversely proportional to amount ingested. Time post-ingestion is also important.<ref name="multiples">http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 31.10.2010 </ref>.
+*'''Dogs:''' Ataxia, mild to severe increasing depression and other neurological signs, tachycardia, tachypnoea, polydypsia, polyuria, dehydration, anorexia, emesis, miosis, hypothermia
-'''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 .<ref name="multiples">http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 31.10.2010 </ref>, <ref name="multiple"> '''BSAVA Manual of Canine and Feline Emergency Care'''(Second Edition 2007)</ref>.
+***if untreated anuric acute renal failure
+*'''Cats:''' Ataxia, pronounced depression and other neurological signs, tachycardia, tachypnoea, polyuria, dehydration, anorexia, emesis, miosis <ref name="multiple">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref>,
+<ref name="multiple">'''BSAVA Manual of Canine and Feline Emergency Care''',Second Edition 2007,Chapter 19</ref>.
+**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
-If untreated coma and death, or if lesser amount ingested oliguric acute renal failure within 2 to 7 days after ingestion .<ref name="Merck online" /><ref name="BSAVA">King, L. and Boag, A. (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care''' (Second Edition), ''BSAVA''</ref>. This will result in anuric acute renal failure if untreated.
-'''Cats:''' Ataxia, pronounced depression and other neurological signs, tachycardia, tachypnoea, polyuria, dehydration, anorexia, emesis, miosis <ref name="5-Minute" /><ref name="BSAVA" />. Coma and death result if untreated, or if lesser amount was ingested, oliguric acute renal failure within 1 day after ingestion. Untreated, this will progress to anuric acute renal failure.
 ===Laboratory Tests===
+*Metabolic Acidosis, increased serum osmolality, increased anion gap, decreased plasma bicarbonate concentration, decreased PCO2, decrease blood pH
-'''Blood:''' ''Metabolic Acidosis'', increased anion gap (as metabolic acidosis is due to increased organic acids rather than loss of bicarbonate<ref name="Ettinger">Ettinger, S.J. and Feldman, E.C. (2010) '''Textbook of Veterinary Internal Medicine''', ''Saunders''</ref>), decreased plasma bicarbonate concentration, decreased PCO2, decreased blood pH, ethylene glycol (in-house colorimetric kit),<ref name="BSAVA" />  although concurrent use of drugs such as diazepam and etomidate both of which contain propylene glycol can confound results<ref name="Ettinger" />. Hyperphosphataemia can be present in later stages due to acute renal failure <ref name="Ettinger" />, and [[hypocalcaemia]] as a consequence of this<ref name="Ettinger" /> and also as a consequence of ionised calcium binding to ethylene glycol metabolites.
+*increased urea and creatinine, hyperkalaemia,
+*Hyperphosphataemia due to acute renal failure <ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>.
-'''Urine:'''increased urea and creatinine, hyperkalaemia, calcium oxalate crystalluria <ref name="BSAVA" />, ethylene glycol (in-house colorimteric kit)<ref name="BSAVA" />.
+**Hypocalcaemia as a consequence of this<ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>.
 ===Ultrasonography===
-Renal accumulation of calcium oxalate crystals results in hyperechogenicity upon ultrasound examination <ref name="Ettinger" />.
+*Renal accumulation of calcium oxalate crystals results in hyperechogenicity upon ultrasound examination <ref name=''multiples''>'''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1968 </ref>.
+===Biopsy===
+*Needle or surgical wedge biopsy of kidney <ref name=''multiples''>'''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1968 </ref>.
-===Biopsy===
+===Pathology===
-Needle or surgical wedge [[Renal Biopsy|biopsy of kidney]]<ref name="Ettinger"/>.
+Ethylene glycol toxicosis usually results from ingestion although there have been reports of skin contamination resulting in toxicosis in cats <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. It is absorbed relatively quickly from the gastrointestinal tract, hence the quick manifestation of clinical signs following intoxication. Following absorption transformation to its more toxic metabolites takes place in the liver and kidney. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body. The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole, is responsible for the initial conversion of ethylene glycol to glycoaldehyde. This reaction, along with the later conversion of glycolic acid to glyoxylic acid, are the rate-limiting steps in the metabolism of ethylene glycol.
+Glycolic acid is one such metabolite. It is a direct metabolite of glycoaldehyde which itself is produced following the actions of the enzyme alcohol dehydrogenase on ethylene glycol.
+*Tetany results from the binding of Ethylene Glycol meatabolites to calcium ions present in serum <ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>.
-===Pathogenesis===
-Ethylene glycol toxicosis usually results from ingestion although there have been reports of skin contamination resulting in toxicosis in cats<ref name="Merck online" />. It is absorbed relatively quickly from the gastrointestinal tract <ref name="Merck online" />, hence the quick manifestation of clinical signs following intoxication. After absorption transformation to its more toxic metabolites takes place in the liver and kidney<ref name="Merck online" />. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body.<ref name="BSAVA" /> The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole <ref name="5-Minute" />, is responsible for the initial conversion of ethylene glycol to glycoaldehyde <ref name="Merck online" />. 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 responsible 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. The metabolic acidosis interferes with normal metabolic pathways. In addition to being directly nephrotoxic oxalate binds ionised calcium in the serum forming calcium oxalate crystals which are excreted by the kidney.<ref name="Merck online" /> 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]].<ref name="Ettinger" />
 ==Treatment==
-'''Prevent further absorption of Ethylene Glycol:''' ''only beneficial if animal presents one to two hours post ingestion''
+*'''Ethanol:''' useful in both dogs and cats <ref name="multiples">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref>.
-:'''Administration of an emetic''' eg syrup of ipecachuanha, apomorphine, sodium carbonate crystals <ref name="BSAVA" />.
-:'''Gastric lavage'''
-:'''Administration of adsorbents''' eg activated charcoal <ref name="Merck online" /><ref name="BSAVA" />
-'''Specific Antidotes that Prevent Metabolism of Ethylene Glycol''' ''benefits dependent of time post ingestion, see prognosis''
+*'''4-methylpyrazole''':''Dogs only'' mode of action is to inhibit ADH in the liver. Recommended doses 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 <ref name="multiples">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref>.
-:'''Ethanol:''' useful in both dogs and cats, <ref name="5-Minute" /> ethanol acts as an antidote by competitively inhibiting alcohol dehydrogenase<ref name="Merck online" />.
-:'''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<ref name="BSAVA" />. Its advantage over ethanol is that it has less side effects and is the treatment of choice in dogs<ref name="BSAVA" />. It acts by directly inactivating the enzyme alcohol dehydrogenase. <ref name="Merck online" />
-'''Promote Excretion of Ethylene Glycol'''
+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.<ref>'''Canine Medicine and Therapeutics''' (Fourth Edition, 1998),''Blackwell Science'', p1049 </ref>
-:'''[[:Category:Fluid Therapy|Fluid therapy]]''' promotes diuresis and helps prevent dehydration<ref name="Merck online" />. Also useful in [[Acute Renal Failure|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.<ref name="Gorman">Gorman, N.T. (1998) '''Canine Medicine and Therapeutics''' (Fourth Edition), ''Blackwell Science'', p1049 </ref>. Also useful in '''management of metabolic acidosis'''.
-'''Management of Acute Renal Failure'''
-:Re-establish normal fluid and electrolyte balance <ref name="5-Minute" />
-:Diuresis, using diuretics eg mannitol <ref name="5-Minute" />
-:Peritoneal Dialysis <ref name="5-Minute" />
 ==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 post-ingestion.<ref name="5-Minute" />
-{{Learning
-|flashcards = [[Feline Medicine Q&A 23]]
-}}
 ==References==
 <references/>
-{{review}}
-{{OpenPages}}
-[[Category:Toxicology]][[Category:Expert Review]][[Category:Urological Diseases - Cat]][[Category:Urological Diseases - Dog]][[Category:Neurological Diseases - Cat]][[Category:Neurological Diseases - Dog]]