Difference between revisions of "Chocolate Poisoning-Dog"
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==Introduction== | ==Introduction== | ||
| − | Toxicity is due to the presence of methylxanthines such as theobromine and caffeine in chocolate | + | 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>. | ||
==Signalment== | ==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 | + | 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, cardiovascular and urological signs | + | 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>. |
| − | <ref name=" | ||
| − | *'''CNS:''' | + | *'''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 | + | |
| − | *''' | + | *'''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>. |
| − | *'''Urological:''' polydypsia and polyuria may also be present <ref name="multiples"> | + | *'''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. The following laboratory tests are possible but not commonly used; | + | 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; |
| − | * | + | |
| − | * Blood Glucose: Hypoglycaemia as a | + | * 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>. |
| − | * Urinalysis: Proteinuria, low specific gravity; not seen consistently with chocolate poisoning <ref name=" | + | * 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=== | ===Other=== | ||
| − | *ECG: rate and rhythm abnormalities | + | *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 | + | 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=" | + | 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''' | + | |
| − | *'''Modulation of Intracellular Calcium Concentrations:''' | + | *'''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> |
| − | 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> | + | *'''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
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
- 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
- ↑ 1.00 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 - ↑ 2.00 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 - ↑ 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
- ↑ 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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