CHOCOLATE (METHYLXANTHINE) TOXICOSIS

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CHOCOLATE (METHYLXANTHINE) TOXICOSIS

 

Chocolate (Methylxanthine) Toxicosis is an acute gastroenteric, neurologic, and cardiac toxicosis is caused by excessive intake of methylxanthine alkaloids present in chocolate. 

Theobromine is the largest fraction of methylxanthines in chocolate products and in cacao bean mulch. A lower concentration of caffeine is also present. Other sources include diet pills, over-the-counter stimulants, and herbal medications

 

PATHOPHYSIOLOGY

Methylxanthines are variably absorbed (caffeine < 1 hour; theobromine 10 hours), metabolized by the liver, excreted in bile, and reabsorbed (enterohepatic cycling).

The estimated theobromine and caffeine half-life in dogs is 17 hours and 4.5 hours respectively.

They cross the placenta and blood-brain barrier; maybe resorbed via the urinary bladder.

Inhibition of phosphodiesterase increases cAMP, potentiating catecholamines and increasing cellular calcium.

Causes vasoconstriction, an increased force of cardiac and skeletal muscle contraction, CNS stimulation, seizures, bronchodilation, and tachycardia.

Toxic doses:

  • Theobromine LD50 (dog) 250–500 mg/kg; LD50 (cat) 200 mg/kg
  • Caffeine LD50 (dog) 140 mg/kg; LD50 (cat) 80–150 mg/kg.
  • Caution: one-tenth of the LD50 may still be a lethal dosage for some animals.

 

SYSTEMS AFFECTED

  • Cardiovascular—increased myocardial contractility and tachyarrhythmias; tachycardia, hypertension, ventricular premature contractions (VPC).
  • Gastrointestinal— early vomiting and diarrhea; may result even from parenteral administration of methylxanthine alkaloids.
  • Metabolic—hypokalemia, hyperthermia.
  • Nervous—stimulation; enhanced alertness and reflex hyperactivity; tremors; tonic-clonic seizures.
  • Renal/Urologic—polyuria, polydipsia.
  • Respiratory—tachypnea, hypoxia, cyanosis, respiratory failure.

 

INCIDENCE/PREVALENCE

Dogs—among 20 most common poisonings in recent literature, reported by small animal practices, and animal and human poison control centers.

More common at holiday times—chocolate products and candies readily available.

Caffeine-containing stimulant tablets, as much as 200 mg/tablet—occasional source.

Cacao bean hull mulch for landscaping—increasing risk for dogs.

 

GEOGRAPHIC DISTRIBUTION

Urban and indoor dogs—may be more at risk owing to close proximity to chocolate products or cacao landscape mulch.

 

SIGNALMENT

Species

Dogs are frequently poisoned based on proximity to methylxanthine products, consuming large doses, and longer half-life of theobromine in dogs (theobromine 17.5 hours vs. caffeine 4.5 hours).

Cats are rarely affected.

Other species likely have more limited access to chocolate; cacao bean hulls are an increasing source in dogs, horses, and poultry.

 

Breed Predilections

Small dogs—may be more at risk (amount of chocolate relative to body weight).

 

Mean Age and Range

Puppies and young dogs—likely to ingest large amounts of unusual foods.

Young animals are typically more compromised in metabolism and excretion.

SIGNS

Historical Findings

  • Recently confirmed chocolate or cacao hull ingestion.
  • Evidence of chewed containers or remnants of packaging from chocolate products.
  • Vomiting and diarrhea—often first reported sign, 2–4 hours after ingestion.
  • Early restlessness and increased activity or nervousness.
  • Polyuria—may result from diuretic action.
  • Hematuria occasionally.
  • Advanced signs—stiffness; excitement; seizures; hyperreflexia.

 

Physical Examination Findings

  • Vomiting and diarrhea followed by a combination of CNS excitation and tachycardia (often extreme) is characteristic.
  • Hyperthermia.
  • Hyperactivity
  • Hyperreflexia.
  • Muscle rigidity.
  • Tonic-clonic seizures.
  • Mydriasis.
  • Tachypnea.
  • Tachycardia (> 200/min).
  • Hypertension.
  • Premature ventricular contractions.
  • Advanced signs—cardiac failure, weakness, cyanosis, coma, and death.
  • Polyuria/polydipsia.
  • Death—12–48 hours after ingestion.

CAUSES

  • Usually processed chocolate (used for candies and baking).
  • Minimum lethal dosage for caffeine and theobromine (dogs)—100–200 mg/kg.
  • Potentially lethal exposure (dogs):
  • 5 g baking chocolate provides 20 mg caffeine and 80 mg theobromine (total 100 mg).
  • A 20 kg dog could be poisoned at 100 g/kg by consuming 5 g chocolate/kg × 20 kg = 100 g chocolate (3.5 oz).
  • Milk chocolate provides only 2 mg of alkaloids per gram (50 g chocolate/kg bw) or nearly 2 oz/kg, which would be 40 oz (2.5 lb) for a 20 kg dog (unlikely amount).
  • Dogs are poisoned by cacao bean hulls (contain both alkaloids) used as landscaping mulch. Several aids to canine risk from chocolate can be found online. See “Internet Resources.”

 

RISK FACTORS

Chocolate—palatable and attractive; often readily available and unprotected in homes and kitchens.

 

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

  • Convulsant or excitatory alkaloids—strychnine; amphetamine; nicotine; 4-aminopyridine; cocaine; tricyclic antidepressants; serotonin syndrome.
  • Metaldehyde snail and slug bait.
  • Acute bromethalin poisoning.
  • Zinc phosphide poisoning.
  • Convulsant pesticides—organochlorines (e.g., chlordane, lindane) and pyrethrins.
  • Tremorogenic mycotoxins—penitrem A; aflatrem; roquefortine.
  • Acute psychogenic drugs—LSD; cocaine; morning glory.
  • Medications (phenylpropanolamine, phenylephrine, pseudoephedrine).
  • Cardioactive glycosides—Digitalis spp.; Nerium oleander.
  • Hypomagnesemia and hypocalcemia.

 

CBC/BIOCHEMISTRY/URINALYSIS

  • Hyperglycemia or hypoglycemia—both have been noted and hence not a reliable indicator.
  • Hypokalemia.
  • Low urine specific gravity and proteinuria.

 

OTHER LABORATORY TESTS

Methylxanthine Assay

Stomach contents, plasma, urine.

Detectable plasma or serum concentration should persist 3–4 days.

Stable in serum samples for 7 days (room temperature), 2 weeks refrigerated.

Theobromine in the serum of poisoned dogs may range from 100 to 300 mg/L.

 

DIAGNOSTIC PROCEDURES

ECG—sinus tachycardia, premature ventricular contractions, and ventricular tachyarrhythmia.

 

PATHOLOGIC FINDINGS

  • Small or large amounts of chocolate in the stomach or intestine.
  • Gastroenteritis—non-specific.
  • No distinctive microscopic lesions.
  • Microscopic renal lesions are not consistent; characterized by hyaline droplet degeneration, pyknosis, and karyorrhexis, potentially from impaired renal perfusion.

 

Table 1 Comparative concentration of caffeine and theobromine.
Caffeine Source Amount (mg/g) Amount (mg/oz)*
Coffee beans 10–20 284–570
Drip coffee 90–100 mg/6 oz. cup Ca. 15
Cola drinks 60–90 mg/12 oz. can 5–8
Baking chocolate Up to 4 Up to 112
Dark chocolate 4–5 135
Milk chocolate 0.2 6
Cocoa Up to 1.5 46
Cacao bean hulls 5–8.5 142–240
Guarana 30–50 850–1,400
Stimulant tablets 200 mg/tablet —————
OTC pain control 60 mg/tablet —————
Theobromine Source Amount (mg/g) Amount (mg/oz)
Cacao beans 10–50 280–1,400
Baking chocolate 14–16 398–454
Milk chocolate 1.5–2 46–57
Cacao bean hulls 5–9 142–256
Cacao bean mulch 2–30 57–852
Cacao powder 14–29 398–832

* To convert mg/g to mg/oz, multiply by 28.4 g/oz.

 

TREATMENT

APPROPRIATE HEALTH CARE

  • By phone—attempt to determine type and amount of exposure; if not possible, refer to hospital as a potential toxicologic emergency.
  • Control seizures.
  • Detoxification (if seizures controlled) using emesis early, or gastric lavage, and activated charcoal; most effective within 2–4 h post-exposure, longer if chocolate remains in the stomach.
  • Give activated charcoal daily up to 3 days to reduce enterohepatic recycling of the alkaloids. Only the first dose of charcoal should contain a cathartic.
  • Control hyperthermia.
  • Treat tachycardia (see “Medications”).
  • Urinary catheterization or frequent urine voiding may reduce urinary bladder resorption.
  • Provide IV fluid therapy to prevent dehydration, promote diuresis, and avoid hypernatremia.
  • Control tremors with methocarbamol or diazepam (see “Medications”). Seizure control may require treatment with diazepam; if not controlled, use either pentobarbital or other general anesthetics (see “Medications”).

 

NURSING CARE

Fluid therapy—correct electrolyte disturbances caused by vomiting.

 

ACTIVITY

Avoid stress and excitement—could precipitate hyperreflexia or seizures.

 

DIET

  • Acutely affected patient—no food.
  • Convalescence—bland diet for several days to allow recovery from gastroenteritis.

 

CLIENT EDUCATION

Warn clients of the hazards of chocolate ingestion.

 

SURGICAL CONSIDERATIONS

Rarely, a mass or concretion of chocolate could form that must be removed surgically.

 

MEDICATIONS

DRUG(S) OF CHOICE

  • Induce emesis—only if patient is not seizing; apomorphine (0.03 mg/kg IV); hydrogen peroxide 3% (1–3 mL/kg PO).
  • Gastric lavage—only before onset of vomiting and other clinical signs, if emetics are not effective, seizures controlled, and endotracheal tube in place.
  • Once vomiting is controlled—activated charcoal (0.5–1 g/kg PO) adsorbs remaining alkaloids in the gastrointestinal tract—repeated at 4- to 8-hour intervals for 1–2 days to prevent enterohepatic recycling.
  • Osmotic cathartic—sodium sulfate (0.25 g/kg PO) or sorbitol 70% at 1–3 mL/kg PO; promotes gastrointestinal elimination of chocolate.
  • Hyperactivity and seizures— control with diazepam (0.5–1 mg/kg IV q10–20min up to 2 times or diazepam CRI at 0.5–1 mg/kg/h).
  • Ventricular tachycardia (dogs)—lidocaine (without epinephrine), 2–4 mg/kg IV followed by 0.03–0.05 mg/kg/min IV drip. Lidocaine is NOT RECOMMENDED in cats.
  • Serious refractory arrhythmias—metoprolol or propranolol (0.02–0.06 mg/kg IV; rate not > 1 mg/minute); metoprolol preferred but may be difficult to obtain; use oral therapy once the patient is stable (metoprolol at 0.2–0.4 mg/kg PO q12h; propranolol at 0.1–0.2 mg/kg PO q8h); monitor the ECG and watch for hypotension as a sequel to this treatment.
  • In the rare instance of bradycardia, use atropine at 0.02–0.04 mg/kg IV, IM, or SC.

 

CONTRAINDICATIONS

  • Do not use epinephrine concurrent with lidocaine.
  • Avoid erythromycin and corticosteroids—these reduce the excretion of methylxanthines.
  • Do not use lidocaine in affected cats.
  • PRECAUTIONS
  • Effects may persist longer than the effective life of therapeutic drugs.
  • Keep patient under observation until drug administration is no longer needed.
  • Methylxanthines—cross the placenta; excreted in milk.

 

ALTERNATIVE DRUG(S)

  • Control of hyperreflexia and muscle rigidity may be obtained with methocarbamol (50–220 mg/kg slowly IV).
  • If the response to diazepam is inadequate—consider phenobarbital (5–8 mg/kg IV administered over 5–10 minutes q4–6h) or propofol titrated to effect.
  • Refractory seizures – pentobarbital coma or mask down with general anesthetic.

 

FOLLOW-UP

PATIENT MONITORING

  • ECG—arrhythmias.
  • Watch for mild to moderate nephrosis in convalescent patients.

 

PREVENTION/AVOIDANCE

Warn owners about the toxicologic hazards of chocolate.

 

POSSIBLE COMPLICATIONS

Pregnant or nursing animals—risk for teratogenesis of newborns or stimulation of nursing neonates.

 

EXPECTED COURSE AND PROGNOSIS

  • Expected course – 12 to 36 hours, depending on dosage and effectiveness of decontamination and treatment.
  • Successfully treated patients—usually recover completely.
  • Prognosis – good if oral decontamination occurs within 2–4 hours of ingestion; guarded with advanced signs of seizures and arrhythmias.

 

MISCELLANEOUS

AGE-RELATED FACTORS

Young animals are typically more compromised in metabolism and excretion.

 

ZOONOTIC POTENTIAL

Not transmissible, but humans and dogs may access similar sources.

 

PREGNANCY/FERTILITY/BREEDING

Methylxanthines are teratogens in laboratory animals.

 

ABBREVIATIONS

CNS = central nervous system

CRI = continuous rate infusion

ECG = electrocardiogram.

 

Word Count (total):   1524

Word Frequency: 

33 (5%)mg 

27 (4%)kg 

21 (3%)chocolate 

11 (2%)theobromine 

11 (2%)cacao 

11 (2%)dogs 

10 (1%)caffeine 

10 (1%)seizures 

9 (1%)hours 

9 (1%)may

 

Visit your veterinarian as early recognition, diagnosis, and treatment are essential.

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