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.<ref name="multiple"> '''BSAVA Manual of Canine and Feline Emergency and Critical Care'''Second Edition,2007 </ref>
 
 
==Signalment==
 
==Signalment==
−
Dog that live indoors are more likely to have access to chocolate.<ref name="multiples">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="multiples">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Second Edition), ''Lippincott, Williams and Wilkins''</ref>. These signs are observed quite quickly after ingestion of toxic amount of chocolate.<ref name="multiple"> '''BSAVA Manual of Canine and Feline Emergency and Critical Care'''Second Edition,2007 </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:''' 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>.
 +
 
 +
*'''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>.
  
−
*'''CNS:''' hyperexcitability, hyperactivity, ataxia initially can evolve into muscle tremors, clonic seizures and hyperthermia.<ref name="multiples">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="multiples">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>
 
−
*'''Cardiovascular:''' arrhythmias,infrequently bradycardia but usually tachycardia.<ref name="multiples">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>
 
 
===Laboratory Tests===
 
===Laboratory Tests===
−
* Detection of methylxanthines in bodily fluids such as plasma, urine and stomach contents <ref name="multiples">Tilley Smith'''The 5-Minute Veterinary Consult Canine and Feline''' (Third Edition), ''Lippincott, Williams and Wilkins''</ref>.
+
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 name="multiple"> '''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:'''<ref name="multiple"> '''BSAVA Manual of Canine and Feline Emergency and Critical Care''' Second Edition,2007</ref>
+
 
 +
*'''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/>
 +
 +
 +
{{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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