Difference between revisions of "Chocolate Poisoning-Dog"

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[[File:Chocolate.jpg|thumb|Chocolate]]
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==Introduction==
 +
Toxicity is due to the presence of methylxanthines such as theobromine and caffeine in chocolate <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>. Concentrations ranging from of 100-250mg/kg of theobromine and 110-200mg/kg of caffeine have been reported to cause fatalities <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.  The consumption of more than 20mg/kg of total methylxanthines, the dose at which mild signs such as vomiting, diarrhoea and polyuria are induced <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>, is considered the cut-off point in deciding whether or not to treat <ref name="multiples"> Warman, SM (2007)Dietary intoxications'''BSAVA Congress 2007 Scientific Proceedings, Veterinary Programme''' ''BSAVA'' </ref>. The concentration of methylxanthines differs between products <ref name="multiples"> Tilley, LP, Smith, FWK'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref> and therefore the number of grammes required to reach this threshold vary according to the product; in a 10kg dog 5000g of white chocolate provides the equivalent 20mg/kg dose of methylxanthines that 12-40g of plain chocolate, 83-117g of milk chocolate or 7-25g of cocoa powder does <ref name="multiples"> Warman, SM (2007)Dietary intoxications'''BSAVA Congress 2007 Scientific Proceedings, Veterinary Programme''' ''BSAVA''</ref>
 +
Methylxanthines are also present in beverages and foods other than chocolates <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
  
==Introduction==
 
Toxicity is due to the presence of methylxanthines such as theobromine and caffeine in chocolate. They are also present in stimulant preparations and other products.
 
 
==Signalment==
 
==Signalment==
Dog that live indoors are more likely to have access to chocolate.<ref name="multiple">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Second Edition), ''Lippincott, Williams and Wilkins''</ref>
+
Dog that live indoors are more likely to have access to chocolate. Also puppies and dogs that scavenge are at a greater risk of eating food that is not intended for their consumption. Small breeds of dogs may reach the toxic level of methylxanthine concentration per body weight more easily  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>.
 
 
  
 
==Diagnosis==
 
==Diagnosis==
 
===Clinical Signs===
 
===Clinical Signs===
Chocolate poisoning results in CNS, gastrointestinal and cardiovascular signs.<ref name="multiple">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Second Edition), ''Lippincott, Williams and Wilkins''</ref>
+
Chocolate poisoning results in CNS, gastrointestinal, cardiovascular, respiratory and urological signs <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>, <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref> which are evident soon after ingestion of a toxic amount of chocolate <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
*'''CNS:''' hyperexcitability, hyperactivity, ataxia initially can evolve into muscle tremors, clonic seizures and hyperthermia.<ref name="multiple">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Second Edition), ''Lippincott, Williams and Wilkins''</ref>, <ref name="multiple">BSAVA Congress 2007 Scientific Proceedings p253-254</ref>
+
 
*'''Gastrointestinal:''' diarrhoea, emesis, haematemesis, colic.<ref name="multiple">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Third Edition), ''Lippincott, Williams and Wilkins''</ref>, <ref name="multiple">BSAVA Congress 2007 Scientific Proceedings p253-254</ref>
+
*'''CNS:''' hyperactivity, behavioural changes, ataxia, muscle tremors, clonic seizures and hyperthermia <ref name="multiple"> Tilley, LP, Smith, FWK '''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>, <ref name="multiples"> Warman, SM (2007)Dietary intoxications'''BSAVA Congress 2007 Scientific Proceedings, Veterinary Programme''' ''BSAVA'' </ref>, <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
*'''Cardiovascular:''' arrhythmias,infrequently bradycardia but usually tachycardia.<ref name="multiple">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Second Edition), ''Lippincott, Williams and Wilkins''</ref>, <ref name="multiple">BSAVA Congress 2007 Scientific Proceedings p253-254</ref>
+
 
 +
*'''Gastrointestinal:''' diarrhoea, emesis, haematemesis <ref name="multiples"> Tilley, LP, Smith, FWK'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>, <ref name="multiples"> Warman, SM (2007)Dietary intoxications'''BSAVA Congress 2007 Scientific Proceedings, Veterinary Programme''' ''BSAVA'' </ref>.
 +
*'''Cardiovascular:''' arrhythmias,tachycardia, bradycardia sometimes, hypotension  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>, <ref name="multiples"> Warman, SM (2007)Dietary intoxications'''BSAVA Congress 2007 Scientific Proceedings, Veterinary Programme''' ''BSAVA'' </ref>.
 +
*'''Respiratory:''' tachypnoea <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>.
 +
*'''Urological:''' polydypsia and polyuria may also be present <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>.
 +
 
 
===Laboratory Tests===
 
===Laboratory Tests===
 +
Diagnosis is usually on the basis of clinical signs and a known history of chocolate ingestion <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>. The following laboratory tests are possible but not commonly used;
 +
 +
* Assays for detection of methylxanthines in bodily fluids such as plasma, urine and stomach contents  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>.
 +
* Blood Glucose: Hypoglycaemia as a sequela to hyperactivity. not seen consistently with chocolate poisoning  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>.
 +
* Urinalysis: Proteinuria, low specific gravity; not seen consistently with chocolate poisoning  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>.
 +
 +
===Other===
 +
*ECG: rate and rhythm abnormalities  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>.
 +
 
===Pathology===
 
===Pathology===
The methylxanthines yield their effects through
+
Following absorption from the gastrointestinal tract caffeine and theobromine are metabolised in the liver <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>. Caffeine has a half life of 4.5 hours in dogs while theobromine has a half life of 17.5 hours <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>. In humans the half life of theobromine ranges from 6 to 10 hours, significantly shorter than that in dogs which may explain the susceptibility of dogs to chocolate poisoning REF.
*'''Antagonism of Adenosine Receptors:'''<ref> '''BSAVA Manual of Canine and Feline Emergency and Critical Care''' Second Edition, 2007</ref>
+
Methylxanthines have the following modes of action.
*'''Inhibition of Cyclic Nucleotide Phosphodiesterase:'''
+
 
 +
*'''Antagonism of Adenosine Receptors:'''<ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref> this antagonism results in stimulation of the central nervous system and an increase in heart rate  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref> and also diureses <ref name="multiples"> '''http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm''', accessed on 04.10.2010 </ref>
 +
*'''Inhibition of Cyclic Nucleotide Phosphodiesterase:'''<ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref> consequently there is an increase in cyclic AMP, which in turn leads to greater catecholamine release and their effects  <ref name="multiple"> Tilley, LP, Smith, FWK ()'''The 5-Minute Veterinary Consult Canine and Feline(Second Edition)''' ''Lippencott, Williams and Wilkins''</ref>.
 +
*'''Modulation of Intracellular Calcium Concentrations:''' <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>.
 +
Ventricular fibrillation, and other cardiac dysrhythmias are most frequently the ultimate cause of death.<ref> Carson TL (2006) Methylxanthines. In: ''Small Animal Toxicology'', ed. ME Peterson, PA Talcott, pp.845-852. Elsevier Saunders, St. Louis in '''BSAVA Manual of Canine and Feline Emergency Care''' Chapter 19, Second Edition,2007 </ref>, <ref> Holmgren P, Norden-Petterson L and Ahlner J (2004)Caffeine fatalaties: four case reports. ''Forensic Science International'' '''139''', 71-73 '''BSAVA Manual of Canine and Feline Emergency Care''' Second Edition,2007 </ref>.
 +
 
 
==Treatment==
 
==Treatment==
 +
'''Of dogs presenting with clinical signs'''
 +
*'''Inital stabilisation of Cardiorespiratory System:'''
 +
**Tachycardia: beta-blockers, eg orally administered metoprolol at a dose of 0.5mg to 1mg per kg every 8 hours <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
 +
**Premature Ventricluar Contractions: lidocaine; iv bolus of 2mg to 6mg per kg administered slowly, after which a constant rate infusion of 20ug to 70ug per kg per minute should be given <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
 +
**Bradycardia: Atropine at a dose of 0.01mg to 0.02mg per kg <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>.
 +
 +
*'''Treatment of seizures and hyperactivity'''
 +
**IV Diazepam at a dose of 0.5 to 2 mg/kg <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
 +
**Alternative to diazepam is barbiturates <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
 +
**Treating the seizures and hyperactivity should help restore normal body temperature. If animal still hyperthermic then this should be treated directly <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
 +
 +
*'''Correction of acid/base and electrolyte inbalances''' <ref name="multiples">Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011</ref>,
 +
 +
*'''Insertion of urinary catheter'''
 +
**Helps prevent further absorption of theobromine and caffeine across bladder wall <ref name="multiple"> King, LG, Boag, A (2007) '''BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition)''' ''BSAVA''</ref>.
 +
 +
 +
'''Of dogs with a known history of recent chocolate ingestion but who have not yet developed clinical signs'''
 +
*Administration of apomorphine (0.03mg/kg IV) or hydrogen peroxide (1-5 ml/kg PO) ref 5 min vet consult in order to induce emesis and/or of activated charcoal in order to minimise further absorption of methylxanthines re 5 min vet consult
 +
 
==Prognosis==
 
==Prognosis==
 +
If treated correctly and early enough ref 5min consult the prognosis is good and a complete recovery can be expected <ref name="multiples"> Warman, SM (2007)Dietary intoxications'''BSAVA Congress 2007 Scientific Proceedings, Veterinary Programme''' ''BSAVA'' </ref>. For animals presenting with seizures and arrhythmias the prognosis is more cautious.
 +
 
==References==
 
==References==
 
<references/>
 
<references/>
<ref name="multiple">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Second Edition), ''Lippincott, Williams and Wilkins''</ref>
+
 
<ref> '''BSAVA Manual of Canine and Feline Emergency and Critical Care''' Second Edition, 2007</ref>
+
 
 +
{{review}}
 +
{{OpenPages}}
 +
[[Category:Toxicology]][[Category:To Do - Major]][[Category:To Do - Neurological]][[Category:To Do - Alimentary]][[Category:To Do - Respiratory]]

Latest revision as of 18:01, 2 January 2013


Chocolate

Introduction

Toxicity is due to the presence of methylxanthines such as theobromine and caffeine in chocolate [1]. Concentrations ranging from of 100-250mg/kg of theobromine and 110-200mg/kg of caffeine have been reported to cause fatalities [1]. The consumption of more than 20mg/kg of total methylxanthines, the dose at which mild signs such as vomiting, diarrhoea and polyuria are induced [2], is considered the cut-off point in deciding whether or not to treat [2]. The concentration of methylxanthines differs between products [2] and therefore the number of grammes required to reach this threshold vary according to the product; in a 10kg dog 5000g of white chocolate provides the equivalent 20mg/kg dose of methylxanthines that 12-40g of plain chocolate, 83-117g of milk chocolate or 7-25g of cocoa powder does [2] Methylxanthines are also present in beverages and foods other than chocolates [1].

Signalment

Dog that live indoors are more likely to have access to chocolate. Also puppies and dogs that scavenge are at a greater risk of eating food that is not intended for their consumption. Small breeds of dogs may reach the toxic level of methylxanthine concentration per body weight more easily [1].

Diagnosis

Clinical Signs

Chocolate poisoning results in CNS, gastrointestinal, cardiovascular, respiratory and urological signs [1], [2] which are evident soon after ingestion of a toxic amount of chocolate [1].

  • CNS: hyperactivity, behavioural changes, ataxia, muscle tremors, clonic seizures and hyperthermia [1], [2], [1].
  • Gastrointestinal: diarrhoea, emesis, haematemesis [2], [2].
  • Cardiovascular: arrhythmias,tachycardia, bradycardia sometimes, hypotension [1], [2].
  • Respiratory: tachypnoea [2].
  • Urological: polydypsia and polyuria may also be present [2].

Laboratory Tests

Diagnosis is usually on the basis of clinical signs and a known history of chocolate ingestion [2]. The following laboratory tests are possible but not commonly used;

  • Assays for detection of methylxanthines in bodily fluids such as plasma, urine and stomach contents [1].
  • Blood Glucose: Hypoglycaemia as a sequela to hyperactivity. not seen consistently with chocolate poisoning [1].
  • Urinalysis: Proteinuria, low specific gravity; not seen consistently with chocolate poisoning [1].

Other

  • ECG: rate and rhythm abnormalities [1].

Pathology

Following absorption from the gastrointestinal tract caffeine and theobromine are metabolised in the liver [2]. Caffeine has a half life of 4.5 hours in dogs while theobromine has a half life of 17.5 hours [2]. In humans the half life of theobromine ranges from 6 to 10 hours, significantly shorter than that in dogs which may explain the susceptibility of dogs to chocolate poisoning REF. Methylxanthines have the following modes of action.

  • Antagonism of Adenosine Receptors:[1] this antagonism results in stimulation of the central nervous system and an increase in heart rate [1] and also diureses [2]
  • Inhibition of Cyclic Nucleotide Phosphodiesterase:[1] consequently there is an increase in cyclic AMP, which in turn leads to greater catecholamine release and their effects [1].
  • Modulation of Intracellular Calcium Concentrations: [2].

Ventricular fibrillation, and other cardiac dysrhythmias are most frequently the ultimate cause of death.[3], [4].

Treatment

Of dogs presenting with clinical signs

  • Inital stabilisation of Cardiorespiratory System:
    • Tachycardia: beta-blockers, eg orally administered metoprolol at a dose of 0.5mg to 1mg per kg every 8 hours [1].
    • Premature Ventricluar Contractions: lidocaine; iv bolus of 2mg to 6mg per kg administered slowly, after which a constant rate infusion of 20ug to 70ug per kg per minute should be given [1].
    • Bradycardia: Atropine at a dose of 0.01mg to 0.02mg per kg [2].
  • Treatment of seizures and hyperactivity
    • IV Diazepam at a dose of 0.5 to 2 mg/kg [1].
    • Alternative to diazepam is barbiturates [1].
    • Treating the seizures and hyperactivity should help restore normal body temperature. If animal still hyperthermic then this should be treated directly [1].
  • Correction of acid/base and electrolyte inbalances [2],
  • Insertion of urinary catheter
    • Helps prevent further absorption of theobromine and caffeine across bladder wall [1].


Of dogs with a known history of recent chocolate ingestion but who have not yet developed clinical signs

  • Administration of apomorphine (0.03mg/kg IV) or hydrogen peroxide (1-5 ml/kg PO) ref 5 min vet consult in order to induce emesis and/or of activated charcoal in order to minimise further absorption of methylxanthines re 5 min vet consult

Prognosis

If treated correctly and early enough ref 5min consult the prognosis is good and a complete recovery can be expected [2]. For animals presenting with seizures and arrhythmias the prognosis is more cautious.

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 King, LG, Boag, A (2007) BSAVA Manual of Canine and Feline Emergency and Critical Care(2nd Edition) BSAVA 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 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 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 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. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 Merck & Co (2008) The Merck Veterinary Manual (Eight Edition), Merial found at http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/211104.htm&word=chocolate%2cpoisoning accessed January 2011 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
  3. Carson TL (2006) Methylxanthines. In: Small Animal Toxicology, ed. ME Peterson, PA Talcott, pp.845-852. Elsevier Saunders, St. Louis in BSAVA Manual of Canine and Feline Emergency Care Chapter 19, Second Edition,2007
  4. Holmgren P, Norden-Petterson L and Ahlner J (2004)Caffeine fatalaties: four case reports. Forensic Science International 139, 71-73 BSAVA Manual of Canine and Feline Emergency Care Second Edition,2007




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