Strychnine Toxicity


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Jenna Otter


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Updated:
3/26/2019 11:31:21 PM

Introduction

Strychnine has been used for hundreds of years as a medicinal remedy for a broad range of ailments. Although it has now become a rare poisoning agent, sporadic ingestions still occur throughout the United States. Strychnine inhibits postsynaptic glycine receptors predominantly in the spinal cord, causing involuntary painful skeletal muscle contractions. Patients present with “awake seizures" which are episodic muscle contractions with no post-ictal period and normal mental status. Treatment is mainly supportive with benzodiazepines and management of complications from excessive muscle contraction. Most patients who survive acute poisoning do not have chronic sequelae of the poisoning.

Etiology

Strychnine poisoning occurs via accidental or intentional ingestion of compounds containing the chemical. Typically, strychnine is used intentionally for suicidal or homicidal means. Strychnine poisoning may also occur unintentionally by ingesting the Chinese or Cambodian herbal remedies, Miqianzi and slang nut, respectively. Commonly, it is found as a white powder and most often is ingested orally, but there are reports of intravenous injection and intranasal insufflation via adulterated heroin and cocaine.[1][2][3]

Epidemiology

The toxin is an alkaloid found in the seeds of the Strychnos nux-vomica plant (See Figure 1), which is native to India, Northern Australia, and the East Indies. In Cambodia and Thailand, it is called “slang nut” or “slang Thai nut.” It is used in several Southeast Asian herbal remedies. In the United States, strychnine has been used in poisons, rodenticides, and performance-enhancing drugs. Low doses of strychnine are thought to have performance-enhancing qualities. The 1904 Olympic marathon winner ingested strychnine mid-race, and the 2016 Olympic weightlifting bronze medalist tested positive for strychnine.[4]

Its use in the United States has been curtailed dramatically in the last century because of cases of poisoning and fatalities from ingestion of products containing strychnine. In the 1930s, it was one of the most common lethal poisonous ingestions of children. As late as the 1980s, strychnine could still be found in over the counter consumer products such as digestive aids, sedatives, stimulants, and cold remedies, although the U.S. Food and Drug Administration ordered its removal from food and medicines in 1962. In 1989, it was outlawed as an indoor pesticide in the United States, but it is still found in outdoor poisons today.[2] The American Association of Poison Control Centers Annual report details 72 exposures and one death from strychnine poisoning in 2015.

Pathophysiology

Strychnine is an alkaloid, colorless, bitter powder. It is a competitive inhibitor of the postsynaptic glycine receptor mostly in the spinal cord. The inhibition of glycine, the primary inhibitory neurotransmitter, causes uncontrolled stimulation of postsynaptic neurons leading to involuntary diffuse muscle contractions. Because it does not affect the higher motor neuron centers, patients typically present with severe muscle contractions that appear as if they are having “awake seizures” or seizures with no postictal period. The mental status will be preserved until late when sequelae of unchecked muscle contractions create hyperthermia, acidosis, and further physiologic derangements.

Symptoms occur between 15 and 30 minutes after oral ingestion, faster through the intranasal or intravenous route. The initial symptom is excitability and heightened awareness followed by vomiting and muscle contractions. Convulsions last from 30 seconds to 2 minutes and take the form of opisthotonic posturing: back arched, extremities extended and jaw clenched (See Figure 2). Patients may demonstrate risus sardonicus, –muscle contractions of the face causing a fixed, stiff appearance of a sardonic smile. Uncontrolled muscle contraction can lead to tachycardia, hyperthermia, airway compromise from stiffness at the jaw and neck, and later findings of rhabdomyolysis, hyperkalemia, lactic acidosis, metabolic acidosis, kidney failure, and seizures. Patients can have a respiratory failure from the airway and respiratory muscle spasm. Unchecked strychnine poisoning can cause death within several hours.[2]

Toxicokinetics

When ingested orally, strychnine is absorbed through the gastrointestinal tract. It has transient detectable levels in the blood but rapidly distributes to the tissues. It is metabolized predominantly in the liver and partially excreted by the kidneys. Strychnine follows first-order kinetics with a half-life of 10 to 16 hours and volume of distribution of 13 L/kg. The median lethal dose is 1.5 mg/kg. Post-mortem assays find highest concentrations in the hepatobiliary system. Urine and gastric measurements are most useful to test for exposure, and blood assays are unreliable.[2]

History and Physical

History should focus on ingestions within the last few hours. History of ingestion of herbal remedies should raise suspicion for strychnine poisoning. Recent cocaine or heroin use can be a useful historical clue, as sometimes illicit drugs are cut with strychnine. Time from exposure should be ascertained to evaluate the usefulness of gastrointestinal decontamination.

The physical exam should be comprised of basic emergency medical evaluation beginning with airway, breathing, and circulation. A temperature should be obtained to assess for hyperthermia from excessive muscle contraction. The airway should be secured if there are signs of respiratory distress. Severe acidosis from muscle contractions may result in paralysis, and respiratory muscle paralysis is a major cause of mortality.

Evaluation

Thin layer chromatography can be performed on gastric aspirate and urine samples to evaluate for strychnine poisoning. Blood testing is unreliable, due to the transient nature in which strychnine is found in the blood after any route of ingestion. Other blood assays should include basic metabolic panel, arterial or venous blood gas, lactate, and urinalysis. Tests should focus on assessing for hyperkalemia, acidosis, rhabdomyolysis, and renal failure.[2]

Treatment / Management

Predominantly, treatment is comprised of supportive care with securing airway with endotracheal intubation as necessary. In ingestions that present acutely within the first few hours, activated charcoal or gastric lavage can be considered. Caution should be used when performing gastrointestinal decontamination as manipulation may provoke seizures.

Barbiturates and benzodiazepines can be used to control muscle contractions in cases of mild to moderate toxicity. Patients should be intubated and paralyzed with nondepolarizing paralytic agents if convulsions are uncontrollable and causing hyperthermia or acidemia. Generous intravenous fluid hydration should be administered for the treatment rhabdomyolysis. If intubation is required for airway protection, succinylcholine should be avoided given the potential for hyperkalemia.[2][5][6][7]

In the case of minor to moderate exposures, recovery is usually complete with no neurologic or musculoskeletal sequelae.

Pearls and Other Issues

Strychnine has been detected in cocaine and heroin (it is a white powder used to “cut” the illicit drug). When inhaled, snorted, or injected, symptoms of strychnine poisoning occur rapidly. Consider strychnine poisoning in a patient with opisthotonic posturing after illicit drug use.[3]

Enhancing Healthcare Team Outcomes

The diagnosis and management of strychnine poisoning is best done with a multidisciplinary team that includes poison control, neurologist, an emergency department physician, ICU nurses, an internist, and a toxicologist. The treatment should follow the ATLS guidelines.  In ingestions that present acutely within the first few hours, activated charcoal or gastric lavage can be considered. Caution should be used when performing gastrointestinal decontamination as manipulation may provoke seizures.

Barbiturates and benzodiazepines can be used to control muscle contractions in cases of mild to moderate toxicity. Patients should be intubated and paralyzed with nondepolarizing paralytic agents if convulsions are uncontrollable and causing hyperthermia or acidemia. Generous intravenous fluid hydration should be administered for the treatment rhabdomyolysis. If intubation is required for airway protection, succinylcholine should be avoided given the potential for hyperkalemia.[2][5] The pharmacist should keep a track of all medications that can worsen the spasms.

Outcomes

In the case of minor to moderate exposures, recovery is usually complete with no neurologic or musculoskeletal sequela. For those who sustain severe neurological or musculoskeletal deficits, the recovery can be prolonged and associated with permanent disability. [8](Level V)


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Attributed To: Contributed by Sir Charles Bell, 1809 (Public Domain)

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Strychnine Toxicity - Questions

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Poisoning with which of the following can mimic refractory seizures?



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Which compound specifically inhibits the glycine receptor?



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A patient presents with uncontrolled convulsions after ingesting a traditional Cambodian herbal remedy more than 4 hours prior to arrival. Blood glucose level, airway, breathing, and circulation are normal. The patient is placed on a monitor that shows sinus tachycardia. What is the next step?



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After ingesting a compound containing strychnine a patient presents with convulsions, risus sardonicus, and preserved mental status. From what part of the plant was strychnine extracted and where are the effects of strychnine at the synapse?



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What precautions should be taken when intubating a patient with strychnine poisoning?



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Strychnine Toxicity - References

References

A Case of Strychnine Poisoning from a Southeast Asian Herbal Remedy., Singhapricha T,Pomerleau AC,, The Journal of emergency medicine, 2017 Apr     [PubMed]
An unusual case of strychnine poisoning., Prat S,Hoizey G,Lefrancq T,Saint-Martin P,, Journal of forensic sciences, 2015 May     [PubMed]
Strychnine poisoning., Smith BA,, The Journal of emergency medicine, 1990 May-Jun     [PubMed]
A case of fatal strychnine poisoning., Dittrich K,Bayer MJ,Wanke LA,, The Journal of emergency medicine, 1984     [PubMed]
Adulterants in illicit drugs: a review of empirical evidence., Cole C,Jones L,McVeigh J,Kicman A,Syed Q,Bellis M,, Drug testing and analysis, 2011 Feb     [PubMed]
Guo R,Wang T,Zhou G,Xu M,Yu X,Zhang X,Sui F,Li C,Tang L,Wang Z, Botany, Phytochemistry, Pharmacology and Toxicity of Strychnos nux-vomica L.: A Review. The American journal of Chinese medicine. 2018;     [PubMed]
Ma L,Gu R,Tang L,Chen ZE,Di R,Long C, Important poisonous plants in tibetan ethnomedicine. Toxins. 2015 Jan 14;     [PubMed]
Shadnia S,Moiensadat M,Abdollahi M, A case of acute strychnine poisoning. Veterinary and human toxicology. 2004 Apr;     [PubMed]

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