Changes

==Signalment==

==Signalment==

*'''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>  

*'''Dogs:''' all ages, both sexes, following intoxication lower incidence of fatalities in dogs compared to cats <ref name="5-Minute" />  

*'''Cats:''' all ages, both sexes

*'''Cats:''' all ages, both sexes

*'''Birds'''

*'''Birds'''

*'''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>

*'''Other:''' including pigs and cattle <ref name="Merck online" />

==Diagnosis==

==Diagnosis==

===Clinical Signs===

===Clinical Signs===

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>.

Severity of clinical signs is inversely proportional to amount ingested. Time post-ingestion is also important.<ref name="Merck online" />

'''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), p286-7 </ref>. This will result in anuric acute renal failure if untreated.

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="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 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.

'''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===

===Laboratory Tests===

'''Blood:''' ''Metabolic Acidosis'', increased anion gap (as metabolic acidosis is due to increased organic acids rather than loss of bicarbonate<ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', ''Ettinger and Feldman'' Seventh Edition p470 </ref>), decreased plasma bicarbonate concentration, decreased PCO2, decreased blood pH, ethylene glycol (in-house colorimetric kit)<ref name="multiples"> '''BSAVA Canine and Feline Emergency Care''', Second Edition (2007), Chapter 19, p286-7 </ref>, although concurrent use of drugs such as diazepam and etomidate both of which contain propylene glycol can confound results<ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1975 <ref/>. Hyperphosphataemia can be present in later stages due to acute renal failure <ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>, and hypocalcaemia as a consequence of this<ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref> and also as a consequence of ionised calcium binding to ethylene glycol metabolites.

'''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. '''Textbook of Veterinary Internal Medicine'''</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.

'''Urine:'''increased urea and creatinine, hyperkalaemia, calcium oxalate crystalluria <ref name="multiples"> '''BSAVA Canine and Feline Emergency Care''', Second Edition 2007, Chapter 19, p286-7 </ref>, ethylene glycol (in-house colorimteric kit)<ref name="multiples"> '''BSAVA Canine and Feline Emergency Care''', Second Edition 2007, Chapter 19, p286-7 </ref>.

'''Urine:'''increased urea and creatinine, hyperkalaemia, calcium oxalate crystalluria <ref name="BSAVA" />, ethylene glycol (in-house colorimteric kit)<ref name="BSAVA" />.

===Ultrasonography===

===Ultrasonography===

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>.

Renal accumulation of calcium oxalate crystals results in hyperechogenicity upon ultrasound examination <ref name=''Ettinger'' />.

===Biopsy===

===Biopsy===

Needle or surgical wedge [[Renal Biopsy|biopsy of kidney]]<ref name=''multiples''>'''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1968 </ref>.

Needle or surgical wedge [[Renal Biopsy|biopsy of kidney]]<ref name=''Ettinger''/>.

===Pathogenesis===

===Pathogenesis===

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 <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>, 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="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body.<ref name="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''', (Second Edition), p286-7 </ref> The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole <ref name="multiple">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref>, is responsible for the initial conversion of ethylene glycol to glycoaldehyde <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. 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<ref name="multiples"> '''http://en.wikipedia.org/wiki/Ethylene_glycol_poisoning#cite_note-Gabow_PA.2C_Clay_K.2C_Sullivan_JB.2C_Lepoff_R_1986_16.E2.80.9320-4''', accessed on 17.10.2010 </ref>. The metabolic acidosis interferes with normal metabolic pathways <ref name="multiples"> '''http://en.wikipedia.org/wiki/Ethylene_glycol_poisoning#cite_note-Gabow_PA.2C_Clay_K.2C_Sullivan_JB.2C_Lepoff_R_1986_16.E2.80.9320-4''', accessed on 17.10.2010 </ref>. 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="multiples> http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref> . 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="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>

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 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. 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==

==Treatment==

'''Prevent further absorption of Ethylene Glycol:''' ''only beneficial if animal presents one to two hours post ingestion''

'''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 <ref name="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''', (Second Edition), p286-7 </ref>.  

:'''Administration of an emetic''' eg syrup of ipecachuanha, apomorphine, sodium carbonate crystals <ref name="BSAVA" />.  

:'''Gastric lavage'''

:'''Gastric lavage'''

:'''Administration of adsorbents''' eg activated charcoal <ref name="multiples"> '''http://www.merckvetmanual.com/mvm/index.jsp''', accessed on 09.12.2010 </ref>, <ref name="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''', (Second Edition), p286-7 </ref>.

:'''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''

'''Specific Antidotes that Prevent Metabolism of Ethylene Glycol''' ''benefits dependent of time post ingestion, see prognosis''

:'''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> ethanol acts as an antidote by competitively inhibiting alcohol dehydrogenase<ref name="multiples"> '''http://www.merckvetmanual.com/mvm/index.jsp''', accessed on 09.12.2010 </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="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''', (Second Edition), p286-7 </ref>. Its advantage over ethanol is that it has less side effects and is the treatment of choice in dogs <ref name="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''',(Second Edition), p286-7 </ref> . It acts by directly inactivating the enzyme alcohol dehydrogenase. <ref name="multiples"> '''http://www.merckvetmanual.com/mvm/index.jsp''', accessed on 09.12.2010 </ref>.

:'''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'''

'''Promote Excretion of Ethylene Glycol'''

:'''[[:Category:Fluid Therapy|Fluid therapy]]''' promotes diureses and helps prevent dehydration <ref name="multiples"> '''http://www.merckvetmanual.com/mvm/index.jsp''', accessed on 09.12.2010 </ref>. Also useful in acute renal failure.

:'''[[:Category:Fluid Therapy|Fluid therapy]]''' promotes diureses 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>'''Canine Medicine and Therapeutics''' (Fourth Edition, 1998),''Blackwell Science'', p1049 </ref>. Also useful in '''management of metabolic acidosis'''.

:'''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'''

'''Management of Acute Renal Failure'''

:Re-establish normal fluid and electrolyte balance <ref name="multiples"> '''The 5 Minute Veterinary Consult''', ''Tilley Smith'', Lippincott, Williams and Wilkins, Canine and Feline Second Edition </ref>.

:Re-establish normal fluid and electrolyte balance <ref name="5-Minute" />

:Diuresis, using diuretics eg mannitol <ref name="multiples"> '''The 5 Minute Veterinary Consult''', ''Tilley Smith'', Lippincott, Williams and Wilkins, Canine and Feline Second Edition </ref>.

:Diuresis, using diuretics eg mannitol <ref name="5-Minute" />

:Peritoneal Dialysis <ref name="multiples"> '''The 5 Minute Veterinary Consult''', ''Tilley Smith'', Lippincott, Williams and Wilkins, Canine and Feline Second Edition </ref>.

:Peritoneal Dialysis <ref name="5-Minute" />

==Prognosis==

==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  <ref name="multiples">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins'' </ref> .

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" />

==References==

==References==

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[[Category:Toxicology]][[Category:Expert Review]][[Category:Urological Diseases - Cat]][[Category:Urological Diseases - Dog]][[Category:Neurological Diseases - Cat]][[Category:Neurological Diseases - Dog]]