Rodenticide Toxicity

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Practice Essentials

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. Before the mid-20th century, heavy metals (arsenic, thallium) were the often-used agents. (See Etiology, Presentation, and Workup.)

Since the mid-20th century, anticoagulant substances have been the mainstays of rodenticide products. In 2017, anticoagulant rodenticides constituted 5185 of the 8930 case mentions of exposure to rodenticides recorded in the National Poison Data System (NPDS), administered by the American Association of Poison Control Centers (AAPCC). (See Epidemiology.)[1]

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.

Alpha naphthyl thiourea

Alpha naphthyl thiourea (ANTU, Dirax) is a rodenticide that can cause pulmonary edema.

Strychnine

Strychnine is a plant alkaloid that, in the past, was used widely as a rodenticide. This agent is not used much today. Consider strychnine toxicity if an individual presents with a generalized seizure-like appearance but without loss of consciousness or extensor posturing with risus sardonicus. Strychnine has been discovered as an adulterant in some street drugs (cocaine, heroin, amphetamines).[2, 3]  Strychnine is usually brought into the United States from other countries where its use as a rodenticide is still legal.

Thallium

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

Arsenic

Arsenic was widely used as a rodenticide until the late 20th century. It may still be found in liquid form in old barns and storage sites.

Barium-containing rodenticides

Worldwide, barium toxicity continues to be occasionally reported. Profound hypokalemia is the most characteristic effect, in addition to abdominal pain, nausea and vomiting, and altered mental status. No commercially available barium-containing rodenticides are currently available in the United States, so exposures are sporadic. The most recent published case of barium toxicity encountered in the United States was due to ingestion of fireworks.[4]

Bromethalin

Bromethalin, which is a neurotoxin, is increasingly used as an alternative to long-acting anticoagulant and cholecalciferol rodenticides. In 2017, AAPCC-NPDS reported 1132 single exposures, with 856 in children aged less than 6 years.[1]  The prognosis for most accidental ingestions appears to be excellent and the effects are generally self-limited. However, a reported ingestion of 17 mg of bromethalin in an adult resulted in altered mental status, increased cerebrospinal fluid pressure, cerebral edema, and death.[5]   

Cholecalciferol-containing rodenticides

Cholecalciferol-containing rodenticides produce hypercalcemia. However, overdoses are not likely to occur with this type of rodenticide because they require extremely large doses to cause toxicity in humans.

Yellow phosphorus

Yellow phosphorus was once used as a rat or roach poison. Exposure to this highly combustible toxin can cause signs and symptoms including a garlic odor, oral burns, vomiting, and phosphorescent, smoking feces.

Warfarin-type anticoagulants

Most rodenticides encountered today are the warfarin-type anticoagulants and the long-acting brodifacoum anticoagulant products. In the United States and various other parts of the world, the long-acting products (known as superwarfarins) have become the most common rodenticide encountered.[1]  In compliance with the 2008 Environmental Protection Agency (EPA) ban on certain rodenticides, in the United States, the last consumer-marketed long-acting anticoagulant rodenticides were produced in 2015. However, pest control professionals can continue to obtain these products. And, as shown by the annual poison center reports, significant numbers of exposures continue to occur, years after these products' discontinuation.

The prolonged anticoagulant effect of superwarfarins presents a challenging and deadly poisoning to manage. In fact, deaths from rodenticide appear to be rare but are almost always associated with exposure to long-acting anticoagulants. 

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.[6, 7]

Zinc Phosphide

Zinc phosphide is a crystalline, dark grey powder mixed into bait. On contact with moisture—such as gastric fluid—zinc phosphide releases phosphine gas. Toxic manifestations include headache, dizziness, vomiting, and difficulty breathing. Phosphine inhibits the electron transport chain in mitochondria, and in sufficient doses can cause multi-system organ failure and death.

Patient education

For patient education information, see Poisoning Treatment and Child Safety Proofing.

Etiology

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:

Epidemiology

In 2017, the AAPCC reported a total of 8494 single exposures to rodenticides to US poison control centers. Of those, 4810 were to long-acting anticoagulant rodenticides, 187 were to warfarin-type anticoagulant rodenticide, and 1132 were to bbromethalin rodenticides. The outcome of rodenticide exposures was generally benign; overall, 7 exposures resulted in major outcomes, and 2 deaths occurred. Of all the exposures reported, 6604 involved children younger than 6 years.[1]  

The vast majority of exposed individuals were children younger than age 6 years, in which case, the exposure was most often unconfirmed. Eighty percent of the long-acting anticoagulant exposures were in children younger than 6 years.[1]

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, from 1999-2003 revealed that rodenticides were involved in 2.5% of all human exposures, or 3.4% of exposures when pharmaceuticals were removed from the sample. Children younger than age 5 years incurred 31% of rodenticide exposures in SINITOX. Twenty-three exposures resulted in death; 20 of these were intentional suicides.[8]

In China, banned tetramethylene disulphotetramine (TMDT) was responsible for 14,000 poisonings with 932 deaths between January 1991 and December 2010.[9]

Prognosis

As long as the proper duration of therapy is used, acute overdoses of anticoagulant rodenticides generally resolve uneventfully.[10] Deaths usually occur when patients present well after exposure when severe sequelae of anticoagulation have already manifested. Patients exposed to herbal-based rodenticides, such as red squill, usually present with only gastrointestinal (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.

PNU 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, the mortality rate is considerable. Phosphorus intoxication produces serious corrosive injuries and may require extensive reconstructive surgery.

With anticoagulant rodenticides, the following complications have been reported:

 

History

Many of the patients presenting with rodenticide ingestions are children who ingest such substances unintentionally and, thus, usually ingest small quantities. The literature relating to such ingestions is prone to the bias that ingestion may not have actually occurred or that it has occurred at such a low dose as to be inconsequential. Thus, determining the treatment of a child on the basis of published literature is potentially dangerous.

Adults who ingest such substances are most likely attempting suicide; however, homicidal poisoning may occur with these agents because of their ready availability. Surreptitious poisoning may occur from exposure to adulterated or contaminated drugs of abuse. The presence of anticoagulation may represent Munchausen syndrome.

Common presenting symptoms after exposure to long-acting anticoagulants include the following:

An organophosphate rodenticide known as TresPasitos, made with the chemical aldicarb and sold illegally in the United States, has been used primarily by Hispanic individuals.[11] People who ingest this toxin may present with symptoms of acetylcholinesterase inhibition.

Additional presentations of rodenticide exposure include the following:

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.

Physical Examination

Anticoagulant rodenticides rarely produce symptoms at all; when they do, however, 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.

Approach Considerations

Obtain the following tests in patients with possible rodenticide poisoning:

Measure prothrombin time (PT) with international normalized ratio (INR) and activated partial thromboplastin time (aPTT) if the ingested substance is an anticoagulant. Possibly consider bleeding time and platelet count measurements in patients with evidence of bleeding. If available, measurement of quantitative coagulation factors may be helpful, and these may be available far before actual analysis for suspect anticoagulant levels. Coagulation studies are expected to be normal in acute exposures to anticoagulants. These patients may require serial testing for 2 days to exclude or confirm toxicity. Abnormal measurements on initial testing suggest the possibility of long-term exposure.

Because the availability of red blood cell 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 is not necessary to guide therapy. Serial levels might only be helpful to estimate the drug half-life and duration of required therapy. In addition, blood tests for arsenic, thallium, mercury, and lead may be useful but are usually considerably time consuming.

Abdominal plain film radiography

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

Consultations

Consult with the regional poison control center or a medical toxicologist for additional information and patient care recommendations.

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

Approach Considerations

For unintentional ingestions of small amounts of an anticoagulant rodenticide, repeat prothrombin time 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 to an anticoagulant rodenticide 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 (see Warfarin and Superwarfarin Toxicity). It may be wise to monitor brodifacoum levels to determine a treatment endpoint.[12] The source of exposure to a superwarfarin should be disclosed to avoid recidivism.

Patients who ingest anticoagulant rodenticides and are discharged when their clotting studies are found to be normal may have delayed symptom onset and may continue to ingest the rodenticide once they are discharged. In these cases, the treating physician is responsible for proving that any sequelae are not the result of a missed opportunity to treat. As previously stated, consult a hematologist or a medical toxicologist for long-term follow-up if a long-acting anticoagulant was ingested.

Prehospital Care

Points to remember in prehospital patient care for rodenticide poisoning include the following:

Evidence-based guidelines on the management of long-acting anticoagulant rodenticide poisoning are available from the AAPCC.[13]

Emergency Department Care

Patients who present with 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.

Gastrointestinal 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.

Severe hemolysis from phosphine gas (released from zinc phosphide) may require exchange transfusion of RBCs.

Other medical therapy depends on identification of specific substances involved. Examples are as follows:

If no coagulopathy or active bleeding is found in the setting of an anticoagulant exposure, prophylactic treatment with vitamin K is absolutely contraindicated. This would potentially mask the onset and severity of an ingestion and would obfuscate the time required for clinical and/or laboratory monitoring.

If a coagulopathy is documented, but without active hemorrhage, institution of vitamin K therapy is suggested (see Warfarin and Superwarfarin Toxicity). Since all of the vitamin K–dependent clotting factors may be affected, the hemolytic factors C and S may be affected early and may cause the presentation to be one of acute thrombosis rather than anticoagulation.[14, 15]

In addition to vitamin K, prothrombin complex concentrates and/or fresh-frozen plasma may be needed to rapidly reverse anticoagulation from warfarin and superwarfarins when patients present with life-threatening hemorrhage (see Warfarin and Superwarfarin Toxicity for an extended discussion regarding treatment).[16]

Medication Summary

Give all patients with rodenticide overdose activated charcoal as soon as possible to prevent further absorption of ingested toxins. Ensure that their airway is protected. 

If a coagulopathy is documented, institution of vitamin K therapy is suggested. However, again, in the absence of documented coagulopathy, empiric vitamin K therapy is contraindicated. Intentional exposure to an anticoagulant rodenticide for suicidal or other reasons may require substantial treatment with very high doses of vitamin K for a protracted period of time, particularly in the face of exposure to one of the superwarfarins.

Activated charcoal (Actidose-Aqua, Char-Caps, Kerr Insta-Char)

Clinical Context:  Activated charcoal is used in the emergency treatment of poisoning caused by drugs and chemicals. A network of pores in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Activated charcoal does not dissolve in water.

This agent 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 activated charcoal within 30 minutes of poison ingestion.

Phytonadione (MEPHYTON)

Clinical Context:  There is no need to begin therapy unless the INR is greater than 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.

Class Summary

Activated charcoal is empirically used to minimize systemic absorption of the toxin. It may be of benefit only if administered within 1-2 hours of rodenticide ingestion.

Neutralize the effects of the anticoagulant rodenticide-induced hemorrhages with vitamin K.

Author

Derrick Lung, MD, MPH, Physician, Department of Emergency Medicine, San Mateo Medical Center; Assistant Clinical Professor, Division of Clinical Pharmacology, Department of Medicine, San Francisco General Hospital; Assistant Medical Director, California Poison Control System, San Francisco Division

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

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

Disclosure: Nothing to disclose.

Acknowledgements

Fred Harchelroad, MD, FACMT, FAAEM, FACEP Director of Medical Toxicology, Allegheny General Hospital

Disclosure: Nothing to disclose.

Assaad J Sayah, MD Chief, Department of Emergency Medicine, Cambridge Health Alliance

Assaad J Sayah, MD is a member of the following medical societies: National Association of EMS Physicians

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

References

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