Anticoagulant Rodenticides

Commonly called “superwarfarins” they cause massive anticoagulation in patients that last from weeks to months. In contrast single ingestions can be benign, particularly in children when it would be extremely rare for them to ingest enough unintentionally as these agents contain a bittering agent.

Toxic Mechanism:

Vitamin K inhibition of clotting factors II, VII, IX and X. Due to higher affinity for vitamin K,2,3 epoxide reductase and higher hepatic accumulation they have increased potency and prolonged duration of action when compared to warfarin.

Toxicokinetics: 

• Completely absorbed following oral administration
• Highly lipid soluble
• High volume of distribution
• Hepatic metabolism and enterohepatic recirculation resulting in prolonged elimination phases (weeks to months)

Resuscitation:

• Rarely required
• Uncontrolled or life threatening haemorrhage:
  • Fresh frozen plasma (10 – 15 ml/kg)
  • Prothrombin complex concentrate (25 – 50 IU/kg)
  • Vitamin K 10 mg intravenous

Risk Assessment

• Single accidental ingestion does not cause significant anticoagulation
• Anticoagulation will result from >0.1 mg/kg of brodifacoum which equates to:
  • 2 g/kg of 0.005% bait
  • 3 x 50 g pellet packs in a 75kg adult
• Other concentrations:
  • A typical concentration is 0.005% = 5 mg/100g
  • Pellet packs of 50 grams contain 2.5 mg of brodifacoum
  • 0.25% concentrates = 250 mg/100g
• INR usually takes 12 hours to rise post ingestion and frequently delayed to 24 – 48 hours. Peak effect occurs at 72 – 96 hours.
• Anticoagulation is usually associated with repeated ingestions and high doses of vitamin K should be anticipated.
• Clinical features:
  • Usually asymptomatic
  • Severe coagulopathy may present as bruising, petechial or puerperal rashes, gingival bleeding, epistaxis, gastrointestinal bleeding or haematuria.
• Children: They need to ingest >30 grams of a 0.005% preparation as a single dose to cause significant anticoagulation. This has never been reported.

Supportive Care

• General supportive measures

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific:
  • INR: This will not change in the first 6 – 12 hours. Check INR every 12 hours for the first 48 hours. Do not start vitamin K until there is evidence of anticoagulation. A normal INR at 48 hours excludes a toxic ingestion.
  • Superwarfarin: Levels are useful to confirm the diagnosis when there maybe diagnostic uncertainty or suspicion of non-accidental injury. Also useful in determining when it is safe to withdraw vitamin K therapy.

Decontamination:

• Activated charcoal is not indicated following accidental ingestions
• Following massive single acute deliberate self-poisoning administer 50 g of activated charcoal within 12 hours of ingestion.

Enhanced Elimination

• Not clinically useful.

Antidote

• Vitamin K is contraindicated prophylactically – this prolongs the need for medical supervision. Only give with proven anticoagulation.
• Vitamin K should be given with proven anticoagulation.
• Titrate vitamin K to an INR <4, often large doses are required for weeks to months.

Disposition

• Minor unintentional ingestions do not require investigation, observation or hospitalisation
• An INR is indicated if there is suspicion of repeated ingestion, abnormal bleeding or a large single ingestion. A normal INR 48 hours post ingestion (or last ingestion) excludes toxicity
• To establish vitamin K dosing patients will require admission to titrate the dose and supervision to observe compliance along with consultation with mental health.

References

• Gunja N, Coggins A, Biddy S. Management of intentional superwarfarin poisoning with long-term vitamin K and brodifacoum levels. Clinical Toxicology 2011; 49:385-390
• Ingels M. Lai C, Tai, W et al. A prospective study of acute, unintentional, pediatric superwarfarin ingestions managed without decontamination.  Annals of Emergency Medicine 2002; 40(1):73-78.
• Murray L et al. Toxicology Handbook 3rd Edition. Elsevier Australia 2015. ISBN 9780729542241
• Shepherd G. Klein-Schwartz W, Anderson BD. Acute unintentional pediatric brodifacoum ingestions. Pediatric Emergency Care 2002; 18(3):174-178.
• Watt BE, Proudfoot AT, Bradberry SM et al. Anticoagulant rodenticides. Toxicological Reviews 2005; 24(4): 259-269.