Anticoagulant rodenticide poisoning: Management

INTRODUCTION — This topic reviews the management of anticoagulant rodenticide (also called long-acting anticoagulant rodenticide; LAAR) poisoning.

The clinical manifestations and diagnosis of anticoagulant rodenticide poisoning and an overview of rodenticide poisonings other than anticoagulant rodenticides is provided separately.

●(See "Anticoagulant rodenticide poisoning: Clinical manifestations and diagnostic evaluation".)

●(See "Overview of rodenticide poisoning".)

INDICATIONS FOR MEDICAL EVALUATION — Not all ingestions of anticoagulant rodenticides warrant medical evaluation. The need for medical evaluation is determined by the clinical circumstances and the potential toxicity of the reported exposure. We consider a nontoxic dose to be <1 mg. However, with most anticoagulant rodenticide ingestions, the exact amount is difficult to determine and the clinical circumstances and type of formulation ingested is used to determine if an exposure is potentially toxic. We encourage determination of toxicity and need for evaluation in consultation with a regional poison control center, whenever possible. (See 'Regional poison control centers' below.)

Our approach to patients after exposure to long-acting or warfarin anticoagulant rodenticides are based upon the guideline published by the American Association of Poison Control Centers as follows [1]:

●Emergency department evaluation – Immediate referral to an emergency department, regardless of estimated dose ingested or exposure, is warranted for all of the following patients:

•Signs of bleeding or bruising (symptomatic patients)

•Intentional exposure (eg, self-harm, misuse, abuse, or malicious intent)

•High dose exposures

Referral of patients with unintentional toxic ingestions (estimated dose >1 mg) or ingestions of an unknown amount for administration of activated charcoal is also appropriate if treatment can be accomplished within one hour of exposure.

Recommendations for further care of these patients based upon clinical findings is discussed below. (See 'Management' below.)

●Outpatient evaluation – Outpatient evaluation and laboratory testing at a facility that is capable of obtaining and providing results within 24 hours for post-exposure monitoring is appropriate for the following asymptomatic patients (see "Anticoagulant rodenticide poisoning: Clinical manifestations and diagnostic evaluation", section on 'Ancillary studies'):

•Unintentional ingestion of or exposure to long-acting rodenticides by patients on anticoagulant therapy (baseline prothrombin time [PT], international normalized ratio [INR], and partial thromboplastin time (aPTT) as soon as possible after ingestion with repeat measurements 48 to 72 hours after exposure)

•Ingestion in a pregnant patient (evaluation by obstetrician or primary care provider on the day of ingestion with measurement of PT/INR at 48 to 72 hours)

•Unintentional potentially toxic dose in patients without bleeding or bruising (evaluation and measurement of PT/INR 48 to 72 hours after exposure)

●Observation at home – Children and older patients with nontoxic ingestions (eg, one handful or less of low concentration cereal baits) do not need evaluation or blood testing and can undergo observation at home. The patient or caregivers should be advised to watch for signs of bleeding (eg, bruising, epistaxis, oral bleeding, hematuria, or hematochezia) and to seek medical attention if they occur. Based upon observational studies, these patients rarely develop coagulopathy or bleeding [2-6]. Furthermore, no serious hemorrhage has been described in such patients.

MANAGEMENT — The management of anticoagulant rodenticide exposure depends upon clinical findings and estimated dose. Consultation with a regional poison control center is encouraged for all exposures. (See 'Regional poison control centers' below.)

Not all patients who ingest an anticoagulant rodenticide warrant medical evaluation. (See 'Indications for medical evaluation' above.)

Nontoxic exposures — Otherwise healthy patients with nontoxic ingestions of anticoagulant rodenticides such as exploratory ingestions in children do not require medical evaluation or laboratory testing. (See 'Indications for medical evaluation' above.)

Pregnant women and patients on anticoagulant therapy warrant further evaluation as discussed separately. (See 'Indications for medical evaluation' above and "Anticoagulant rodenticide poisoning: Clinical manifestations and diagnostic evaluation", section on 'Acute or chronic exposure'.)

Toxic exposures — Toxic exposures warrant timely evaluation for gastrointestinal decontamination and are subsequently managed based upon whether coagulopathy or bleeding are present.

Gastrointestinal decontamination — We recommend that patients who have ingested toxic amounts of anticoagulant rodenticides receive activated charcoal (AC) orally as long as the following conditions are met:

●Normal mental status and no aspiration risk

●Ingestion of an estimated dose that is >1 mg of anticoagulant rodenticide

●AC can be administered within one hour of ingestion

For patients who present more than one hour after ingestion the use of activated charcoal should be individualized based upon the amount of rodenticide ingested, the potential for adverse effects of AC, and presence of other factors (eg, coingestants) that may slow gastric emptying. AC is unlikely to be of significant benefit more than two hours after ingestion, but may be warranted later in large ingestions where even marginally diminished dose may confer benefit. This recommendation for AC is based upon indirect evidence that AC slows absorption of ingested toxins and that AC binds compounds like warfarin and superwarfarins. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Evidence of efficacy and adverse effects'.)

Evidence is lacking to support the use of whole bowel irrigation (WBI) with polyethylene glycol electrolyte solution (1 to 2 L/hr via naso- or oro-gastric tube) following anticoagulant rodenticide poisoning, and these products do not exhibit sustained-release toxicokinetics. However, it may be an option for very large ingestions or ingestions of intact packets of bait cereal. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Whole bowel irrigation'.)

Gastric lavage has no role in the management of anticoagulant rodenticide poisoning and is of limited usefulness following poisoning in general. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Gastric lavage'.)

No coagulopathy — Patients with normal coagulation testing at 48 hours are not at risk of developing coagulopathy or bleeding. Further care should focus on poisoning prevention in patients with unintentional exposures and identification and treatment of psychiatric disease in patients intending self-harm. (See 'Intentional exposures' below.)

Coagulopathy but no bleeding — The management of coagulopathy but no bleeding varies by type of rodenticide as follows:

●Superwarfarin poisoning – In the otherwise healthy patient with no bleeding, treatment should center on the measurement of prothrombin time (PT) and international normalized ratio (INR). An INR of <4.5 in a patient with no bleeding warrants only observation and serial monitoring. Based upon experience with this degree of anticoagulation in patients on warfarin anticoagulant therapy, the risk of spontaneous bleeding is low for these patients. However, they should be told to modify activities to avoid the risk of falls or head trauma until they have normal coagulation. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'INR <4.5 without bleeding'.)

In otherwise healthy patients with an INR ≥4.5 and no bleeding, we suggest treatment with oral vitamin K₁ rather than intravenous vitamin K₁ to avoid the risk of anaphylaxis associated with intravenous administration. There is little agreement as to dosing. A starting oral dose of 10 mg per day with ongoing monitoring of coagulation status is a reasonable approach. Pediatric dosing should begin at 1 to 2.5 mg orally, however more may be needed depending on the dose of anticoagulant ingested. We measure the INR every 48 to 72 hours and progressively increase the oral dose until the INR <1.5. In case reports, required daily doses of vitamin K₁ range from 15 to 600 mg for 30 to 200 days, with widely varied endpoints [7-12]. These patients also warrant modification of activities to avoid trauma. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'INR 4.5 to 10 without bleeding'.)

There is little agreement as to duration and approach to cessation of vitamin K₁ therapy. We advise consultation with and referral to a hematologist for long-term management. Either tapering the dose or cessation of vitamin K₁ followed by measurement of coagulation parameters 48 to 72 hours following the dosing change are reasonable approaches [13]. Coagulation parameters must be measured for several weeks after cessation to ensure no relapse of coagulopathy or bleeding [7]. This approach is based upon experience with supratherapeutic INR of ≥4.5 in patients receiving warfarin who are at higher risk of bleeding. Some experts advocate for weekly measurement of quantitative superwarfarin (ie, LAAR) concentrations and continue vitamin K₁ until <10 ng/mL [7,9,14]. Use of these assays provide a clear end-point to therapy and obviates the need to monitor coagulation parameters following cessation of vitamin K₁, but they are not widely available [15].

Patients on anticoagulant therapy should have cessation or adjustment of their regimen and receive oral vitamin K₁ based upon their INR in consultation with the prescribing physician and a hematologist.

Vitamin K₁ tablet formulations are very expensive, and supplies can quickly be depleted in a mass poisoning outbreak. Oral administration of injectable vitamin K₁ preparations has been previously used effectively and safely under these circumstances [16,17]. If oral vitamin K₁ is unavailable in sufficient quantities, we suggest consultation with a clinical pharmacist and poison control center. (See 'Regional poison control centers' below.)

●Warfarin poisoning – After ingestion of a warfarin rodenticide, patients who are not on warfarin chronically and who have an INR >10 should receive 2.5 to 5 mg vitamin K₁ orally with reassessment of the INR in 24 hours to determine need for an additional dose. Patients with an INR ≤10 are at lower risk of bleeding and in most instances, avoidance of further warfarin exposure is sufficient. However, vitamin K₁ 1 to 2.5 mg is an option for patients who are at increased risk of bleeding (table 1). (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of supratherapeutic INR without bleeding'.)

Patients on warfarin therapy who ingest warfarin-containing rodenticides should have their regimen managed and oral vitamin K₁ administered with input from their prescribing physician and a hematologist according to the degree of INR elevation.

Coagulopathy and active bleeding — Consultation with a hematologist and medical toxicologist is advised for any patient with bleeding after ingestion of an anticoagulant rodenticide. These patients warrant modification of activities to avoid the risk of falls or head trauma until their coagulopathy is controlled.

●Minor bleeding - Patients with minor bleeding (eg, limited epistaxis or ecchymosis) should receive vitamin K₁ orally. Dosing is much higher and must continue for a longer period of time after superwarfarin ingestion than when vitamin K₁ is given for reversal of excess warfarin. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Minimal bleeding'.)

●Major bleeding – We recommend that patients with life-threatening bleeding (eg, intracranial, genitourinary, or gastrointestinal hemorrhage) following anticoagulant rodenticide poisoning emergently receive 4-factor prothrombin complex concentrate (PCC), if available, or 3-factor PCC and either recombinant factor VIIa or fresh frozen plasma (FFP). If neither 3-factor nor 4-factor PCC is available, then FFP should be given by rapid infusion [2,18,19]. Intravenous vitamin K₁ should also be given but does not have an immediate effect on restoring normal coagulation. This recommendation is derived from limited observational evidence in patients with major bleeding after anticoagulant rodenticide poisoning or warfarin overdose. Patients with major bleeding should be on bed rest.

The following table summarizes the initial emergency treatment of warfarin anticoagulation for life-threatening hemorrhage in adults and provides a suggested approach that is also applicable to anticoagulant rodenticide poisoning (table 2). This approach and the supporting evidence are further discussed separately. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding'.)

Dosing of reversal agents for pediatric patients is as follows:

•PCC (3- or 4-factor) – 25 to 50 international units/kg (maximum dose 2000 international units)

•FFP – 15 to 30 mL/kg (maximum single dose 2 units)

•Factor VIIa – 20 mcg/kg without maximum dose (as for congenital factor VII deficiency)

•Vitamin K₁ – 0.3 mg/kg intravenously (maximum single dose 10 mg)

Elimination enhancement — After absorption of anticoagulant rodenticides has occurred, there are limited efficacy data for enhanced elimination of these compounds. Thus, techniques such as multiple dose activated charcoal, hemodialysis, or cholestyramine are not typically used [2,20-22]. Of these, only cholestyramine has been shown to enhance elimination of warfarin or superwarfarin compounds from the gastrointestinal tract based upon small pharmacokinetic studies in healthy adults and one case report that used duration of coagulopathy as an endpoint [21,22].

Intentional exposures — Patients who ingest anticoagulant rodenticides to harm themselves warrant psychiatric consultation once they are medically stable and prior to hospital discharge. (See "Suicidal ideation and behavior in adults" and "Suicidal ideation and behavior in children and adolescents: Evaluation and management".)

Children who have been intentionally given anticoagulant rodenticides have suffered physical abuse. They warrant evaluation by a child abuse specialist and team and should be reported to child protection agencies. (See "Medical child abuse (Munchausen syndrome by proxy)", section on 'Management'.)

Adults who ingest anticoagulant rodenticides to feign a medical illness require psychiatric referral. (See "Factitious disorder imposed on self (Munchausen syndrome)".)

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

In addition, some hospitals have clinical and/or medical toxicologists available for bedside consultation and/or inpatient care. Whenever available, these are invaluable resources to help in the diagnosis and management of toxic exposures.

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse" and "Society guideline links: Anticoagulation".)

SUMMARY AND RECOMMENDATIONS

●Indications for medical evaluation – The need for medical evaluation after anticoagulant rodenticide ingestion is determined by the clinical circumstances and the potential toxicity of the reported exposure. We consider a nontoxic dose to be <1 mg. However, with most anticoagulant rodenticide ingestions, the exact amount is difficult to determine and the clinical circumstances and type of formulation ingested is used to determine if an exposure is potentially nontoxic or toxic. We encourage determination of toxicity and need for evaluation in consultation with a regional poison control center. (See 'Indications for medical evaluation' above and 'Regional poison control centers' above.)

●Nontoxic exposures – Otherwise healthy patients with nontoxic ingestions of anticoagulant rodenticides such as exploratory ingestions in children do not require medical evaluation or laboratory testing. (See 'Nontoxic exposures' above.)

●Toxic exposures - These warrant timely evaluation for gastrointestinal decontamination and are subsequently managed based upon whether coagulopathy or bleeding are present. (See 'Toxic exposures' above.)

Consultation with a hematologist and medical toxicologist is advised for any patient with bleeding after ingestion of an anticoagulant rodenticide. (See 'Regional poison control centers' above.)

Patients with normal coagulation testing at 48 hours are not at risk of developing coagulopathy or bleeding. (See 'No coagulopathy' above.)

•Gastrointestinal decontamination – In a patient who has ingested a toxic amount of anticoagulant rodenticide, we administer activated charcoal (AC) orally as long as the following conditions are met (Grade 1B) (see 'Gastrointestinal decontamination' above):

-Normal mental status and no aspiration risk

-Ingestion of an estimated dose that is >1 mg of anticoagulant rodenticide

-AC can be administered within one hour of ingestion

In a patient who presents more than one hour after ingestion, we individualize the decision to administer AC based upon the amount of rodenticide ingested, the potential for adverse effects of AC, and presence of other factors (eg, coingestants) that may slow gastric emptying.

•Patients with coagulopathy without bleeding – In the otherwise healthy patient with no bleeding after ingesting a superwarfarin, treatment should center on the measurement of prothrombin time (PT) and international normalized ratio (INR). These patients warrant modification of activities to avoid trauma. There is little agreement as to vitamin K₁ dosing and duration of therapy. (See 'Coagulopathy but no bleeding' above.)

The evidence for this approach is presented elsewhere. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Treatment of supratherapeutic INR without bleeding'.)

-An INR of <4.5 in a patient with no bleeding warrants only observation and serial monitoring.

-In otherwise healthy patients with an INR ≥4.5 and no bleeding, we administer oral vitamin K₁ rather than intravenous vitamin K₁ to avoid the risk of anaphylaxis associated with intravenous administration.

-In a patient with an INR >10 and who is not taking warfarin regularly, we administer 2.5 to 5 mg vitamin K₁ orally with reassessment of the INR in 24 hours to determine need for an additional dose.

-A patient who takes warfarin regularly and ingests a warfarin-containing rodenticide should have their regimen managed and oral vitamin K₁ administered with input from their prescribing physician and according to the degree of INR elevation as discussed separately.

•Patients with coagulopathy and active bleeding – In a patient with life-threatening bleeding following anticoagulant rodenticide poisoning, we recommend administering a 4-factor prothrombin complex concentrate (PCC), if available, or 3-factor PCC and either recombinant factor VIIa or fresh frozen plasma (FFP) (Grade 1C). If neither 3-factor nor 4-factor PCC is available, then FFP should be given by rapid infusion (table 2). Intravenous vitamin K₁ should also be given but does not have an immediate effect on restoring normal coagulation. Patients with major bleeding warrant hospitalization and bed rest until their coagulopathy is controlled. (See 'Coagulopathy and active bleeding' above.)

Patients with minor bleeding should receive vitamin K₁ orally. Dosing is much higher and must continue for a longer duration after superwarfarin ingestion than when vitamin K₁ is given for reversal of supratherapeutic INR due to warfarin. If available, weekly measurement of quantitative superwarfarin concentrations can be helpful to guide duration of therapy.