Strychnine Poisoning

Strychnine Poisoning

Introduction

            Strychnine is a bitter indole alkaloid obtained from the seeds of the Indian tree Strychnos nux-vomica and Strychnos ignatii.. These vine-like trees are indigenous to some southeast Asian countries and northern Australia. All parts of S. nux-vomica and S. ignatii may contain strychnine and brucine (dimethoxystrychnine), a related but less potent alkaloid. Dried seeds from S. nux-vomica have been used to make extracts, powders, and tinctures of strychnine alkaloid. These preparations have been used as bitters, cathartics, tonics, stimulants, and ruminatorics in the past, but now their use is considered ineffective and dangerous. The strychnine content of the dried seeds usually varies from 1% to 2%. Strychnine-containing baits are mostly used to poison birds, gophers, mice, moles, rats, rabbits, porcupines, and wild carnivores such as coyotes, foxes, and wolves. Bait pellets or strychnine-laced grains are usually dyed green or red. Strychnine is highly toxic to most domestic animals. Its oral LD₅₀ in dogs, cattle, horses, and pigs is between 0.5-1 mg/kg, and in cats is 2 mg/kg. Malicious or accidental strychnine poisoning, occurs mainly in small animals, especially dogs and occasionally cats, and rarely in livestock. Malicious or accidental strychnine poisoning cases have been described in several animal species.

Pathogenesis

            Strychnine is ionized in an acidic pH and then rapidly and completely absorbed in the small intestine. It is metabolized in the liver by microsomal enzymes. In vitro studies indicate that cytochrome P-450 monooxygenase is the predominant metabolic enzyme involved and that strychnine-N-oxide is the major metabolite. Strychnine does not appear to concentrate in nervous tissues. The highest concentration of strychnine is found in the blood, liver, or kidney. Strychnine and its metabolites are excreted in the urine. About 10% to 20% of the parent compound appears unchanged in the urine within 24 hours. Depending on the quantity ingested and treatment measures taken, most of the toxic dose is eliminated within 24-48 hr. The approximate lethal dose in dogs and cats is 0.75 mg/kg and 2 mg/kg, respectively.

           

Strychnine inhibits competitively and reversibly the inhibitory neurotransmitter glycine at postsynaptic neuronal sites in the spinal cord and medulla. This results in unchecked reflux stimulation of motor neurons affecting all the striated muscles, resulting in generalized rigidity and tonic-clonic seizures. 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.

Clinical Findings

            The onset of strychnine poisoning is fast. Signs normally appear within 10 minutes to two hours after oral administration. Presence of food in the stomach can delay onset. Early signs, which may often be overlooked, consist of apprehension, nervousness, tenseness, and stiffness. Vomiting usually does not occur. Severe tetanic seizures may appear spontaneously or may be initiated by stimuli such as touch, sound, or a sudden bright light. An extreme and overpowering extensor rigidity causes the animal to assume a “sawhorse” stance. The tetanic convulsions may last from a few seconds to ~1 min. Respiration may stop momentarily. Intermittent periods of relaxation are seen during convulsions but become less frequent as the clinical course progresses. During convulsions, the animal exhibits opisthotonos, the forelimbs are extended, the pupils are dilated, the eyeballs protrude, and the mucous membrane color is cyanotic. Frequency of the seizures increases, and death eventually occurs from exhaustion or asphyxiation during seizures. If untreated, the entire syndrome may last only 1-2 hr. There are no characteristic necropsy lesions. Sometimes, due to prolonged convulsions before death, agonal hemorrhages of heart and lung and cyanotic congestion from anoxia may be seen. Animals dying from strychnine poisoning have rapid rigor mortis.

            Postmortem examination reveals no characteristic lesions. Patients that have prolonged convulsions before death may exhibit agonal hemorrhages of the heart and lungs and cyanotic congestion due to anoxia. Death usually results from respiratory arrest and exhaustion from prolonged seizures.

Diagnosis

            Strychnine poisoning can be tentatively diagnosed based on a history of exposure, typical clinical signs (rapid onset of muscular rigidity, tonic seizures, sawhorse stance, rapid rigor mortis), and a lack of postmortem lesions. Poisoned animals may have undigested red or green strychnine-laced seeds or grain such as peanuts, wheat, milo, or barley in their stomach. Analytical detection of strychnine alkaloid in the vomitus, stomach content, liver, kidneys, or urine should be considered diagnostic. In living animals, the best chance of finding strychnine alkaloid is in stomach content (in vomitus or through stomach washings) or in urine if samples are collected within the first several hours of exposure. Urine samples may not contain detectable amounts of strychnine if they are collected one or two days after exposure. Samples (stomach content, liver, or kidney) should be sealed in a plastic bag, frozen, and submitted to a veterinary diagnostic laboratory for strychnine analysis.

            Strychnine poisoning can be confused with - and should be ruled out from - several other types of poisonings such as metaldehyde, chlorinated hydrocarbon pesticides, zinc phosphide, fluoroacetate, nicotine, 4-aminopyridine, organophosphate pesticides, carbamate pesticides, permethrin (in cats), and tremorgenic mycotoxins such as penitrem A and roquefortine or human medications (tricyclic antidepressants, 5-fluorouracil, metronidazole, isoniazid). Acute, massive hepatic necrosis (hepatic encephalopathy) can also produce clinical signs that resemble those of strychnine poisoning.

Treatment

            Strychnine poisoning is an emergency, and treatment should be instituted quickly. Treatment should be aimed at decontamination, control of seizures, prevention of asphyxiation, and supportive care.

            Since strychnine is a rapidly acting convulsant, most animals presented to a veterinarian are already exhibiting clinical signs. Do not attempt decontamination in animals that are already showing neurologic effects. Control seizures and stabilize the animal first before decontamination.

           

Decontamination consists of removal of gastric contents by inducing emesis or gastric lavage or enterogastric lavage, and binding of remaining bait in the GI tract with activated charcoal. If exposure is recent and no clinical signs are present, emesis should be induced with 3% hydrogen peroxide (small animals and pigs) at 1-2 mL/kg, PO, maximum 3 tbsp, repeated once after 30 min if no vomiting; apomorphine (dogs only) at 0.03 mg/kg, IV, or 0.04 mg/kg, IM; or xylazine (dogs or cats) at 0.5-1 mg/kg, IV or IM. If emesis cannot be induced, gastric lavage should be performed with tepid water. Animals that are already seizuring should be anesthetized first (with pentobarbital) and an endotracheal tube passed before gastric lavage. Use gravity to instill and to drain the liquid, and repeat until the lavage fluid becomes clear. Use large bore tubes and multiple flushes for better results. Enterogastric lavage. Enterogastric lavage, also called a through and through, begins with gastric lavage followed by an enema under low pressure and continues until fluids exit through the gastric tube. Give a preanesthetic dose of atropine (0.02 to 0.04 mg/kg subcutaneously, intramuscularly, or intravenously) before the procedure to relax the patient's intestinal muscles and allow fluids to flow easily. After emesis or gastric lavage, activated charcoal should be administered at 2-3 g/kg mixed with water to make a slurry in small animals and 0.5-1 g/kg in large animals with a cathartic such as sorbitol (70% solution at 1 to 2 ml/kg) or magnesium sulfate at 250 mg/kg, PO.

Seizure control

            If convulsions are present or imminent, intravenous pentobarbital sodium is the drug of choice in small animals. It should be given to effect and repeated as often as necessary. In large animals, chloral hydrate or xylazine can be used to control seizures. Muscle relaxants such as methocarbamol (100 to 200 mg/kg intravenously; repeat as needed up to a maximum dose of 330 mg/kg/day) or guaifenesin (5% solution at 110 mg/kg intravenously) can be tried. Diazepam and xylazine have been used to control strychnine seizures in dogs with variable success. Propofol (3 to 6 mg/kg intravenously or 0.1 mg/kg/min as an infusion) can also be tried. Isoflurane inhalation anesthesia can be used if seizures are not controlled with the preceding treatment measures.

Supportive care

            Severely affected dogs should be intubated and artificial respiration provided. Acidification of urine with ammonium chloride (100 mg/kg, b.i.d., PO) may be useful for ion-trapping and urinary excretion of the alkaloid. Fluids (5% mannitol in 0.9% saline) should be administered to force diuresis and maintain normal kidney function. Monitor and correct the animal's acid-base balance as needed. Maintain the animal's body temperature within the normal range. In strychnine-poisoned dogs, hyperthermia can occur as result of severe muscle fasciculation or seizures. Aggressive cooling, by means of ice baths or cold water enemas, may result in hypothermia and should be avoided. All cooling measures should be stopped when rectal temperature reaches 102^oF (38.9^oC) to prevent rebound hypothermia. Keep affected animals in a dark quiet room until they have recovered. Most animals may require one to three days of treatment.