Strychnine Toxicosis in Animals

Strychnine is ionized in the acidic pH of the stomach and then rapidly and completely absorbed in the small intestine. It may also be absorbed dermally and through the mucous membranes.

The highest concentrations of strychnine in the body are found in the blood, liver, and kidneys. It has a high volume of distribution (13 L/kg).

Strychnine is metabolized in the liver by microsomal enzymes. It has low protein binding.

Strychnine and its metabolites are excreted in the urine. Depending on the quantity ingested and treatment measures taken, most of the toxic dose is eliminated within 24–48 hours.

Strychnine competitively and reversibly inhibits the inhibitory neurotransmitter glycine at postsynaptic neuronal sites in the spinal cord and medulla. This results in unchecked reflex stimulation of motor neurons affecting all the striated muscles. Because the extensor muscles are relatively more powerful than the flexor muscles, they predominate to produce generalized rigidity and tonic-clonic seizures. Death results from anoxia and exhaustion.

The oral median lethal dose (LD₅₀) of strychnine is 0.5–1 mg/kg in dogs, cattle, horses, and pigs and 2 mg/kg in cats.

The onset of toxicosis from strychnine toxicosis is rapid. After oral exposure, clinical signs may appear within 10–120 minutes. Presence of food in the stomach can delay onset. Early clinical signs, which often are overlooked, consist of apprehension, nervousness, tenseness, and stiffness. Extensor rigidity causes the animal to assume a sawhorse stance with splayed, stiff legs. Vomiting is possible but uncommon. Severe tetanic seizures may appear spontaneously or may be initiated by stimuli such as touch, sound, or a sudden bright light. Respiration may stop momentarily. Intermittent periods of relaxation are seen during convulsions but become less frequent as the clinical course progresses.

The mucous membranes become cyanotic and the pupils dilated. Rhabdomyolysis and secondary renal failure may occur due to prolonged muscle activity. Hyperthermia (40°–41°C [104°–106°F]) due to stiffness and seizures often occurs in dogs. Frequency of the seizures increases, and death eventually occurs secondary to respiratory paralysis and hypoxia. If untreated, the entire syndrome may last only 1–2 hours.

There are no characteristic lesions at postmortem examination, but, because of prolonged convulsions before death, petechial hemorrhages of heart and lungs and generalized tissue congestion from anoxia may occur. Animals dying from strychnine toxicosis have rapid rigor mortis.

Tentative diagnosis of strychnine toxicosis is usually based on history of exposure and clinical signs.

Given the necessity of rapid, aggressive treatment, prolonged turnaround times limit the utility of laboratory testing for clinical diagnosis. Confirmation of strychnine alkaloid via various analytical methods (eg, thin-layer chromatography, high-performance liquid chromatography, gas chromatography, and mass spectrometry) from the stomach contents, vomitus, liver, kidneys, or urine should be considered diagnostic. Stomach contents appear to be the most reliable sample for diagnosis but multiple sample types should be collected and analyzed if available. Occasionally, poisoned animals may show presence of undigested grain-laced red or green strychnine bait in the stomach.

Strychnine toxicosis can resemble other causes for tremors and seizures such as metaldehyde; tremorgenic mycotoxins (penitrem a or roquefortine); tetanus; bromethalin; organochlorine, organophosphate, or carbamate insecticides; fluoroacetate (1080); zinc phosphide; nicotine; 4-aminopyridine; caffeine; plant ingestion (Taxus spp, Dicentra spp, Cicuta spp, certain mushrooms)or medications for humans (tricyclic antidepressants, 5-fluorouracil, metronidazole, isoniazid). Primary neurologic disease, acute, massive hepatic necrosis (hepatic encephalopathy), hypoglycemia, and severe metabolic diseases can also produce clinical signs that resemble those of strychnine toxicosis. A CBC and serum biochemical analysis are recommended to help rule out other causes.

There is no specific antidote for strychnine toxicosis.

Decontamination consists of removal of gastric contents by inducing emesis or gastric lavage, and binding of remaining bait in the GI tract with activated charcoal. Because of the rapid onset of clinical signs, emesis may be of limited value in most cases. If exposure is recent and no clinical signs are present, emesis should be induced for gastric decontamination. In dogs and pigs, emesis can be induced with 3% hydrogen peroxide (1–2 mL/kg up to a maximum dose of 45 mL, PO, repeated once after 15–20 minutes if vomiting has not occurred).In dogs only, emesis can be induced with apomorphine (0.03 mg/kg, IV, or 0.04 mg/kg, IM). In cats, emesis can be induced with dexmedetomidine (7 mcg/kg, IM or 3.5 mcg/kg, IV). If emesis cannot be induced, gastric lavage should be performed with tepid water. Animals should be anesthetized first and an endotracheal tube passed before gastric lavage. After emesis or gastric lavage, activated charcoal (1–2 g/kg, PO, in small animals; 0.5–1 g/kg, PO, in large animals) with a cathartic should be administered.

Seizures should be controlled with anticonvulsants. Pentobarbital was historically recommended but is not readily available, so other anticonvulsants should be used. Phenobarbital (4 mg/kg, IV, every 20–30 min to effect up to a maximum 24-hour dose of 20 mg/kg) can be used. Other anticonvulsants such diazepam (0.5–2 mg/kg, IV, to effect or 0.5 mg/kg, per rectum) or levetiracetam (30–60 mg/kg, IV) can be administered for seizure control but may have variable success.

Muscle relaxants such as methocarbamol (55–220 mg/kg, IV, to effect) should be administered; dosing should be repeated as needed or a constant rate infusion can be used. Total doses may need to exceed the maximal recommended cumulative dose of 330 mg/kg/d. The patient will need to be monitored closely for respiratory depression if using high doses of anticonvulsants and methocarbamol.

In large animals, diazepam, phenobarbital, or xylazine can be used to control seizures. Propofol (3–6 mg/kg, IV, or 0.1–0.6 mg/kg/min as a constant-rate IV infusion) can also be tried to control seizures in dogs or cats. Isoflurane inhalation anesthesia can be used in small animals if preceding measures to control seizures do not work.

External stimulation should be limited as it can worsen clinical signs. Severely affected animals should be intubated, and manual or mechanical ventilation provided. Acidification of urine with ammonium chloride (100 mg/kg, PO, every 12 hours) may be useful for ion trapping and urinary excretion of the alkaloid. Intravenous fluids should be administered for diuresis, to prevent pigmentary nephropathy, and maintain normal renal perfusion. Hyperthermia treatment (eg, IV fluids, fans, or cool bath) should be administered if necessary until body temperature is < 39.7°C (103.5°F). Acid-base balance should be monitored and corrected as needed if not responsive to fluid therapy. Most clinical cases require 1–3 days of treatment.

Intravenous lipid emulsion therapy (0.5-1.5 mL of 20% sterile lipid solution/kg, IV as a bolus, followed by 0.25–0.5 mL/kg/min, IV as a CRI, for 30-60 minutes; may be repeated in 6–12 hours) has been used to treat strychnine toxicosis.