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Author: Steven Marcus, MD, Professor, Department of Preventive Medicine and Community Health, Associate Professor, Department of Pediatrics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey; Executive and Medical Director, New Jersey Poison Information and Education System; Consulting Staff, Departments of Pediatrics and Internal Medicine, University Hospital, University of Medicine and Dentistry of New Jersey; Consulting Staff, Department of Pediatrics, Newark Beth Israel Medical Center

Steven Marcus is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Clinical Toxicology, American Academy of Pediatrics, American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association, and Medical Society of New Jersey

Editors: Assaad J Sayah, MD, Chief, Department of Emergency Medicine, Cambridge Health Alliance; John T VanDeVoort, PharmD, ABAT, Director of Pharmacy, Sacred Heart Hospital; Fred Harchelroad, MD, FACMT, Chair, Department of Emergency Medicine, Director of Medical Toxicology, Department of Emergency Medicine, Associate Professor, Allegheny General Hospital; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Author and Editor Disclosure

Synonyms and related keywords: red squill, strychnine, thallium, arsenic, barium-containing rodenticides, cholecalciferol-containing rodenticides, yellow phosphorus, warfarin-type anticoagulants, brodifacoum, alphanaphthyl thiourea, ANTU, sodium monofluoroacetate, N-3-pyridylmethyl-Np-nitrophenyl urea, PNU, Vacor, zinc phosphide, bromethalin, norbormide, cyanide, rodenticide ingestion, rodenticide toxicity, rodenticide poisoning

Background

Rodenticides are a heterogeneous group of compounds that exhibit markedly different toxicities to humans and rodents. They are among the most toxic substances regularly found in homes. The varieties of rodenticides used over the years are legion, leading to the popular expression, "to build a better mousetrap." Before the mid twentieth century, heavy metals (arsenic, thallium) were the often used agents. Since the mid century, anticoagulant substances have been the mainstays of rodenticide products.

Red squill

The botanical preparation of red squill, containing a cardiac glycoside as an active ingredient, was used as a rodenticide for many years. In theory, rodents ingest the product, and because they are incapable of vomiting, develop glycoside intoxication and pulmonary edema. Because humans are capable of vomiting, red squill was considered harmless, even to children. This product is not used much today because of its limited effectiveness as a rodenticide. Alphanaphthyl thiourea (ANTU) is another rodenticide that is said to produce pulmonary edema in rodents but not in higher mammals.

Strychnine

Strychnine is a plant alkaloid that, in the past, was used widely as a rodenticide. This agent is not used much today but is reported to have caused 3 deaths in 1998. Consider strychnine toxicity if an individual presents with generalized seizure like appearance but without loss of consciousness or extensor posturing with risus sardonicus. Strychnine is also used as an adulterant in some street drugs sold as lysergic acid diethylamide (LSD).

Thallium

Although thallium is not licensed for use in the United States, many case reports document thallium intoxications in third world countries where this product is still used as a rodenticide. Consider thallium toxicity when treating a patient with a neuropathy and hair loss. Recent cases of thallium poisoning associated with malicious criminal activity have been reported in the United States.

Arsenic

Arsenic, the poison used in the classic play Arsenic and Old Lace, was widely used as a rodenticide until 2 decades ago. It may still be found in liquid form in old barns and storage sites. (Actually, the victims in the play were probably dispatched with strychnine not arsenic, despite the title).

Barium-containing rodenticides

Interest in these rodenticides is purely academic. No commercially available barium-containing rodenticides are currently available in the United States.

Cholecalciferol-containing rodenticides

Cholecalciferol-containing rodenticides produce hypercalcemia. However, overdoses are not likely to occur with this type of rodenticide because these products are not commonly available, and they require extremely large doses to create a toxicologic situation in humans.

Yellow phosphorus

Yellow phosphorous was once used as a rat or roach poison. Symptoms include a garlic odor, oral burns, vomiting, and phosphorescent smoking feces.

Warfarin-type anticoagulants and brodifacoum

The emergency physician should be familiar with the rodenticides used historically; however, most rodenticides encountered today are the warfarin-type anticoagulants and the long-acting brodifacoum anticoagulant products. In 2002, the most frequently involved rodenticides in cases reported to the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers (AAPCC) were the superwarfarin rodenticides, which accounted for more than 16,000 cases. 

In the United States, as elsewhere in the world, the introduction of the long-acting, also known as superwarfarin, products has become the most common rodenticide encountered. The long-lived nature of the anticoagulation has presented a significant and increasingly difficult to manage problem. In 2005, only 400 cases of simple warfarin-containing rodenticides were reported to the national AAPCC database, while 14,740 superwarfarin exposures were noted. Additionally, although with the warfarin exposures, only one major outcome was reported, in the superwarfarin exposures, 26 major outcomes and one death were reported.

Reports have been documented of rodenticide lacing of marijuana in an effort to enhance the effects. Individuals using this combination have been reported to have coagulopathies as a result.1, 2

Pathophysiology

Rodenticides that are toxic to virtually every organ system in the body have been available.

Cyanide, once prevalent but no longer used for rodenticide application, poisons the cytochrome system.

Effects of other rodenticides are as follows:

  • Poison the Krebs cycle (eg, sodium monofluoroacetate)
  • Destroy the pancreatic beta cell (eg, N-3-pyridylmethyl-Np-nitrophenyl urea [PNU], Vacor)
  • Serve as antagonists of the neurotransmitter glycine at the postsynaptic spinal cord motor neuron (eg, strychnine)
  • Drive potassium intracellularly, may lead to hypotonia (eg, barium)
  • Cause chemical burns (eg, yellow phosphorous)
  • Combine with sulfhydryl groups, thus blocking numerous enzymatic reactions and cell signaling pathways (eg, arsenic)
  • Destroy RBC by hemolysis (eg, zinc phosphide)
  • Uncouple oxidative phosphorylation (eg, bromethalin)
  • Lead to vasoconstriction with ischemia (eg, norbormide)
  • Block the production of vitamin K-dependent coagulation factors (more commonly found than other rodenticide applications)

The warfarinlike anticoagulants and their long-acting progeny produce toxicity by preventing the activation of vitamin K and, hence, its utilization in the production of prothrombin.

Frequency

United States

The predominant rodenticide exposures during the last few years have been anticoagulant rodenticides, generally the superwarfarin type. In 2005, the AAPCC reported a total of 18,011 reports of rodenticide exposure to US poison control centers. Of these, nearly 82% were anticoagulants and 95% of these were of the superwarfarin type. The outcome of these exposures was generally benign; however, 26 of the superwarfarin exposures resulted in a major effect and one death from such an exposure occurred. Over the past 3 years, a slight decline in such exposures has occurred, but the reports of significant morbidity in the literature seem to be increasing.

International

Aggregate tabulations for worldwide experience are not available; however, limited data are available from individual countries or regions. The report of the Brazilian National Poisoning Information System, SINITOX, revealed that rodenticides were involved in 2.5% of all human exposures or 3.4% of exposures when pharmaceuticals are removed from the sample. Children younger than 5 years incurred 31% of rodenticide exposures in SINITOX. Twenty-three exposures resulted in death; 20 of these were intentional suicides.

Mortality/Morbidity

  • The vast majority of rodenticide exposures are to anticoagulants.
  • According to the 2005 TESS data, of the warfarin-type rodenticide exposures, only 30% were treated in a health care facility; 97% of these were exposures to the long-acting superwarfarins. These later individuals experienced 26 major effects and 1 death, while the warfarin-exposed group showed only 1 individual with a major effect and no deaths.
  • The vast majority of exposed individuals were children younger than 6 years, in which case, the exposure was most often unconfirmed. Eighty-eight of the long-acting anticoagulant exposures were in children younger than 6 years, and 81% of the warfarin products were also the agent involved in children younger than 6 years.

Race

No scientific data indicate that outcomes of exposure to any of the rodenticides are based on race.

Sex

No scientific data indicate that outcomes of exposure to any of the rodenticides are based on sex.

Age

According to the 2003 AAPCC annual report, 85% of the rodenticide exposures occurred in children younger than 6 years, 3% occurred in those aged 6-19 years, and almost 11% occurred in adults older than 19 years.3



History

  • Many of the patients presenting with rodenticide ingestions are children who ingest such substances by accident and, thus, usually ingest small quantities. The literature relating to such ingestions is prone to the bias that an ingestion may not have actually occurred or it occurred at such a low dose as to be inconsequential. Thus, determining the treatment of a child based on published literature is potentially dangerous.
  • Adults who ingest such substances are most likely attempting suicide; however, poisoning homicides may occur with these agents because of their ready availability. The presence of anticoagulation might represent Munchausen syndrome.
  • There is a report that it is "common practice" to "lace marijuana and normal tobacco cigarettes with rodenticide in order to achieve a prolonged high." Thus, individuals may present with a clinical picture suggesting an anticoagulant overdose but deny intentional exposure.1, 2
  • The most common presenting symptoms are flank pain with or without frank hematuria and excess bleeding or bruising after relatively minor or no apparent trauma.
  • Verifying the specific rodenticide is important.
    • In the United States, the rodenticide is most likely an anticoagulant.
    • Quite a few of the other rodenticides have been used over the years but are currently not popular.
    • Recently, a new rodenticide called tres pasidas has been found, used primarily by Hispanic individuals. People who ingest these products may present with symptoms of acetyl cholinesterase inhibition.
    • Barium may cause headache, weakness, nausea, abdominal pain, or shortness of breath.
    • Vacor (ie, PNU) may cause people to complain of nausea, vomiting, abdominal pain, or dizziness.
    • Individuals exposed to thallium may report acute GI distress and subsequent anorexia, myalgias, painful neuropathy, and hair loss.
    • Those ingesting strychnine may report anxiety, muscle twitching, or uncontrolled facial grimacing.
    • Zinc phosphide inhalation leads to marked shortness of breath as pulmonary edema develops.
    • High doses of arsenic cause nausea, vomiting, bloody diarrhea, and garlic taste in the mouth.

Physical

  • Anticoagulant rodenticides rarely produce symptoms at all; however, when they do, symptoms are usually delayed. Evidence of frank bleeding, bruising, or other coagulopathy may be present if a significant exposure has occurred. The presence of petechiae under a blood pressure cuff may alert the nursing staff or ED physician to such coagulopathy.
  • Characteristic odors are associated with certain rodenticides.
    • Vacor has an odor of peanuts.
    • Zinc phosphide smells of rotting fish.
    • Organophosphates, such as tres pasidas, smell like garlic.



Acute Respiratory Distress Syndrome
Diabetic Ketoacidosis
Disseminated Intravascular Coagulation
Gastroenteritis
Hypocalcemia
Hypokalemia
Pediatrics, Gastroenteritis
Pediatrics, Gastrointestinal Bleeding
Plant Poisoning, Glycosides - Coumarin
Respiratory Distress Syndrome, Adult
Salmonella Infection
Snake Envenomations, Rattle
Toxicity, Ammonia
Toxicity, Arsenic
Toxicity, Chlorine Gas
Toxicity, Clonidine
Toxicity, Cyanide
Toxicity, Fluoride
Toxicity, Hydrogen Sulfide
Toxicity, Mushroom - Disulfiramlike Toxins

Other Problems to be Considered

Congenital deficiency in clotting factor VII may present with bleeding associated with an abnormal prothrombin time (PT) but a normal activated partial thromboplastin time (aPTT). At first, this may appear to be anticoagulation from a rodenticide or Coumadin; however, with the marked prolongation in PT, some abnormality in aPTT should be present, except in specific factor VII deficiency.



Lab Studies

  • Measure PT and aPTT if the ingested substance is an anticoagulant. Possibly consider bleeding time and platelet count measurements in patients with evidence of bleeding. Requesting quantitative coagulation factors may be helpful and available far before actual analysis for suspect anticoagulant levels.
  • Because the availability of RBC cholinesterase is so poor, do not depend on supporting laboratory evidence when an exposure to an organophosphate-containing substance is suspected.
  • Laboratory verification of the anticoagulant rodenticides (eg, brodifacoum, difenacoum) is available; however, the result takes several days and does not guide therapy.
  • Blood tests for arsenic, thallium, mercury, and lead may be useful but are usually considerably time consuming.
  • Obtain pregnancy tests in women of childbearing age.

Imaging Studies

  • If a metal rodenticide (eg, thallium, arsenic, barium) is considered, using an abdominal plain film x-ray may be helpful because these metals are radio-opaque.



Prehospital Care

  • As in most poisoning situations, it is best to "scoop and run;" very little can be done in the field.
  • Always look for a container so that the specific product can be determined.
  • Decontamination may be necessary for situations in which patients and their garments may be contaminated with the pesticide.

Emergency Department Care

  • Patients who present or develop renal failure may require hemodialysis.
  • Patients with severe respiratory compromise from zinc phosphide, arsenic, or barium may require endotracheal intubation for ventilatory support.
  • Severe hemolysis from phosphine gas (released from zinc phosphide) may require exchange transfusion of RBCs.
  • GI evacuation is rarely useful; however, consider it for exceptional cases in which a huge overdose is suspected and in which the patient presents early to an emergency facility.
  • Give all patients with rodenticide overdose activated charcoal as soon as possible to prevent further absorption of ingested toxins. With anticoagulant overdoses, perform a careful physical examination to look for any sign of bleeding.
  • Other medical therapy depends on identification of specific substance involved.
  • Other medical therapy depends on identification of specific substances involved.
    • If a heavy metal is suspected, institute chelation therapy (see Toxicity, Arsenic; Toxicity, Thallium).
    • If an organophosphate is suspected, administer atropine for initial management and consider oxime use (see Toxicity, Organic Phosphorous Compounds and Carbamates).
    • Monosodium fluoroacetate and zinc phosphide have no specific antidotal therapy that has been of any consistent advantage. Only supportive care is available.
    • Vacor (PNU) induces an alloxan like destruction of pancreatic beta cells, which may be prevented with nicotinamide.
    • If a coagulopathy is documented, institution of vitamin K therapy is suggested. If frank bleeding occurs, the administration of fresh frozen plasma and concentrated clotting factors, may be warranted. Since all of the vitamin Kdependent clotting factors may be affected, the hemolytic factors C and S may be affected early and might cause the presentation to be one of acute thrombosis rather than anticoagulation.4, 5

Consultations

Consult with the regional poison control center or a medical toxicologist (certified through the American Board of Medical Toxicology or the American Board of Emergency Medicine) for additional information and patient care recommendations.

  • Obtain a psychiatric evaluation if the ingestion was intentional.
  • Consult a hematologist or medical toxicologist for long-term follow-up if a long-acting anticoagulant (eg, brodifacoum) was ingested.



The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antidote

Treat anticoagulant rodenticide-induced hemorrhages with vitamin K.

Drug NamePhytonadione (AquaMEPHYTON)
DescriptionNo need to begin therapy unless INR >2. No data exist to prove that such therapy prevents anticoagulation, although vitamin K therapy is shown to reverse anticoagulation once it develops. With long-acting anticoagulants, treatment may need to be at much higher doses and for a protracted period of time.
Adult Dose10-25 mg PO/IM q8h
With long-acting anticoagulants, doses exceeding 100 mg/d for weeks may be indicated
Pediatric Dose1-5 mg PO/IM q8h
ContraindicationsDocumented hypersensitivity
InteractionsAntagonizes effects of warfarin sodium and dicumarol; sucralfate may decrease PO absorption
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsIf bleeding continues despite the administration of vitamin K, consider use of FFP and clotting factor concentrates; caution if considering IV administration because of possibility of allergic reactions; caution in anticoagulated patients for existing clotting concerns (eg, AFib, myocardial valvulopathy)

Drug Category: GI decontaminant

Empirically used to minimize systemic absorption of the toxin. May only be of benefit if administered within 1-2 h of ingestion.

Drug NameActivated charcoal (Liqui-Char)
DescriptionEmergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
May be administered with a cathartic (eg, 70% sorbitol), except in young pediatric patients in whom electrolyte disturbances may be of concern.
For maximum effect, administer within 30 min of ingesting poison.
Adult Dose1 g/kg (50-100 g) PO
Pediatric Dose1-2 g/kg (15-30 g) PO
ContraindicationsDocumented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway with absent gag reflex
InteractionsMay inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties)
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsMonitor for presence of bowel sounds to minimize risk of charcoal ileus; not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administration; after emesis with ipecac syrup, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black



Further Inpatient Care

  • For unintentional small ingestions of an anticoagulant rodenticide, repeat PT measurements 24 and 48 hours post ingestion to ensure that no effects on the coagulation pathway are present. This may be done on an outpatient basis if no other reason for inpatient hospitalization exists.
  • Intentional exposure either for suicidal or other reasons may require substantial treatment with vitamin K for a protracted period of time, particularly in the face of exposure to one of the superwarfarins.
  • Source of exposure to the superwarfarins should be disclosed to avoid recidivism.

In/Out Patient Meds

Treatment of rodenticide-associated coagulopathy may require higher doses of vitamin K as usually encountered and for a protracted period of time. It may be wise to monitor brodifacoum levels to determine a treatment endpoint.6

Complications

  • With anticoagulant rodenticides, the following have been reported:
    • Spontaneous intra-abdominal hemorrhage
    • Hematuria
    • Hematemesis
    • Spontaneous hemoperitoneum
    • Intracerebral hemorrhage
    • Death

Prognosis

  • Anticoagulant rodenticide overdoses are usually relatively simple to treat and patients generally recover. Exposures to herbal-based rodenticides, such as red squill, usually present with only GI symptoms, which are also easy to treat, and full recovery is expected.
  • Metal rodenticides produce serious toxicity and many produce long-term sequelae. Thallium and arsenic are responsible for severe peripheral neuropathies and fatalities have occurred; thus, the prognosis is guarded and depends on the speed of response.
  • Vacor produces a permanent insulin-dependency syndrome. An autonomic neuropathy is not unusual, further complicating the therapy of diabetes.
  • Fluoroacetate and zinc phosphide intoxications are potentially fatal. With no true antidote therapy, fate becomes a deciding factor. The mortality rate is considerable.
  • Phosphorus intoxication produces serious corrosive injuries and may require extensive reconstructive surgery.

Patient Education



Medical/Legal Pitfalls

  • Patients who ingest anticoagulant rodenticides and are discharged when their clotting studies are found to be normal may have a delayed onset in symptoms and may continue to ingest the rodenticide once they are discharged. In these cases, the treating physician is responsible for proving that any sequela is not the result of a missed opportunity to treat.
  • Failure to determine the actual ingested rodenticide, incorrectly assuming that it was an anticoagulant and thereby making an incorrect diagnosis and failing to treat correctly are pitfalls.



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Toxicity, Rodenticide excerpt

Article Last Updated: Nov 6, 2007