Difference between revisions of "Ethylene Glycol Toxicity"

Revision as of 14:56, 9 September 2011

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]. 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 ^[3], ^[3]. 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

Blood: Metabolic Acidosis, increased anion gap (as metabolic acidosis is due to increased organic acids rather than loss of bicarbonate^[1]), 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 resultsCite 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].

Pathogenesis

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].

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].

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.^[6]. Also useful in management of metabolic acidosis.

Management of Acute Renal Failure

Re-establish normal fluid and electrolyte balance ^[1].

Diuresis, using diuretics eg mannitol ^[1].

Peritoneal Dialysis ^[1].

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

↑ ^1.00 ^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 ^1.32 ^1.33 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 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
↑ Feline Medicine and Therapeutics
↑ ^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
↑ 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

[multiples-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 ^1.32 ^1.33 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 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

[multiple-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

[1]

[2]

[3]

[4]

[6]

@@ Line 1: / Line 1: @@
 ==Introduction==
 Ethylene Glycol is a sweet tasting fluid that is the main constituent of anti-freeze products.<ref name="multiples">'''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, although any animal is susceptible to ethylene glycol toxicosis. <ref name="multiples">'''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>. 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 <ref name="multiples">'''The 5-Minute Veterinary Consult, Canine and Feline''', ''Lippencott, Williams and Wilkins''</ref>, <ref name="multiples">http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 20.11.2010 </ref>.
 ==Signalment==
@@ Line 12: / Line 11: @@
 ===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>.
-*'''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>.
+'''Dogs:''' Ataxia, mild to severe increasing depression and other neurological signs, tachycardia, tachypnoea, polydypsia, polyuria, dehydration, anorexia, emesis, miosis, hypothermia
-***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>.
+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.
-**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
+'''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.
 ===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"> '''Testbook 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="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.
-*'''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="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>.
 ===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=''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>.
+Needle or surgical wedge [[Renal Biopsy|biopsy of kidney]]<ref name=''multiples''>'''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1968 </ref>.
-===Pathology===
-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>.
+===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>
 ==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="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''', (Second Edition), p286-7 </ref>.
-**'''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="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>.
-*'''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>. 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 <ref name="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''',(Second Edition), p286-7 </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="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>. 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 <ref name="multiples">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins'' </ref>. 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 <ref name="multiples"> '''http://www.merckvetmanual.com/mvm/index.jsp''', accessed on 09.12.2010 </ref>. 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.<ref>'''Canine Medicine and Therapeutics''' (Fourth Edition, 1998),''Blackwell Science'', p1049 </ref>. Also useful in management of metabolic acidosis ''see below''
-*'''Management of Metabolic Acidosis'''
+'''Specific Antidotes that Prevent Metabolism of Ethylene Glycol''' ''benefits dependent of time post ingestion, see prognosis''
-**'''Sodium Bicarbonate:''' Amount required (mEq) is calculated using the following; 0.3 - 0.5 X body weight (kg) X (24 - plasma bicarbonate) <ref name="multiples"> '''The 5 Minute Veterinary Consult''', ''Tilley Smith'', Lippincott, Williams and Wilkins, Canine and Feline Second Edition </ref>.
+:'''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>.
+:'''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>.
-*'''Management of Acute Renal Failure'''
+'''Promote Excretion of Ethylene Glycol'''
-**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>.
+:'''[[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.
-**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>.
+:'''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'''.
-**Peritoneal Dialysis <ref name="multiples"> '''The 5 Minute Veterinary Consult''', ''Tilley Smith'', Lippincott, Williams and Wilkins, Canine and Feline Second Edition </ref>.
+'''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>.
+: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>.
+:Peritoneal Dialysis <ref name="multiples"> '''The 5 Minute Veterinary Consult''', ''Tilley Smith'', Lippincott, Williams and Wilkins, Canine and Feline Second Edition </ref>.