What is the management of rodenticide poisoning in the ICU with a normal Prothrombin Time (PT) International Normalized Ratio (INR)?

Management of Rodenticide Poisoning in ICU with Normal PT/INR

In rodenticide poisoning with a normal PT/INR, immediate treatment is NOT required, but serial PT/INR monitoring at 24-48 hours post-exposure is mandatory, as anticoagulant rodenticides (particularly long-acting "superwarfarins" like brodifacoum) can cause delayed coagulopathy that may not manifest for 24-72 hours after ingestion. 1, 2

Initial Assessment and Monitoring Strategy

Timing of Coagulopathy Development

• The clinical picture of rodenticide poisoning characteristically shows absence of signs and symptoms during the first 24 hours, with 72.73% of patients manifesting toxidrome after a lag period of 24-36 hours (range 18-72 hours) 2
• First clinical signs of bleeding may be delayed for days (warfarin) or days to months (long-acting anticoagulants like brodifacoum, bromadiolone, difenacoum) after large ingestions 1
• Measure INR at 36-48 hours post-exposure; if normal at this time, even with long-acting formulations, no further action is required 1

Why Normal INR Doesn't Rule Out Future Toxicity

• Long-acting anticoagulant rodenticides ("superwarfarins") have unusually long biological half-lives due to high lipid solubility, enterohepatic circulation, and hepatic accumulation 1
• These agents inhibit vitamin K₁-2,3 epoxide reductase, blocking synthesis of clotting factors II, VII, IX, and X, but this effect takes time to manifest as existing clotting factors are depleted 1
• Greater potency results from higher affinity for vitamin K epoxide reductase and ability to disrupt the vitamin K cycle at multiple points 1

ICU Management Protocol

Immediate Actions (First 24 Hours)

• Gastric decontamination within 2 hours of exposure significantly improves survival (97.87% vs 84.62%) 2
• Activated charcoal administration to prevent absorption if presenting within appropriate timeframe 3
• Establish IV access and initiate supportive care 4
• Baseline laboratory studies: PT/INR, aPTT, complete blood count, comprehensive metabolic panel, liver function tests 2

Serial Monitoring Requirements

• Repeat PT/INR at 24,48, and 72 hours post-exposure minimum 1, 2
• Monitor for clinical signs of bleeding: epistaxis, gingival bleeding, bruising, hematomas, hematuria, gastrointestinal bleeding, menorrhagia 1
• Laboratory monitoring should include AST, ALT, bilirubin, creatinine, and metabolic panel as hepatotoxicity can occur (particularly with yellow phosphorus-containing rodenticides common in some regions) 2

Treatment Thresholds Based on INR Values

If INR Remains Normal (<1.5)

• Continue observation for minimum 48-72 hours 1
• No vitamin K therapy required 1
• Discharge safe if INR normal at 48 hours for long-acting anticoagulants 1

If INR Becomes Elevated Without Bleeding

• INR <4.0: No treatment required, continue monitoring 1
• INR ≥4.0: Administer phytonadione (vitamin K₁) 10 mg intravenously (100 mcg/kg for children) 1
• For anticoagulant-induced prothrombin deficiency, initial dose is 2.5-10 mg, up to 25 mg initially, with some cases requiring 50 mg 5
• Improvement in INR takes 1-8 hours after vitamin K administration; evaluate INR after 6-8 hours and repeat dose if INR remains prolonged 5

If Active Bleeding Occurs

• Immediate administration of prothrombin complex concentrate (PCC) 50 units/kg (contains factors II, VII, IX, X) 1
• Alternative: Recombinant activated factor VII 1.2-4.8 mg 1
• If PCC unavailable: Fresh frozen plasma 15 mL/kg 1
• Plus phytonadione 10 mg IV (100 mcg/kg for children) 1

Critical Pitfalls and Special Considerations

Common Errors to Avoid

• Do not discharge patients with normal initial INR without 48-hour follow-up monitoring, as delayed coagulopathy is characteristic of long-acting anticoagulants 1, 2
• Avoid relying solely on INR for bleeding risk assessment, as the INR was designed and validated only for vitamin K antagonist monitoring, not as a general predictor of bleeding 6
• Delayed resuscitation beyond 2 hours significantly increases mortality risk 2

Predictors of Poor Outcome

• Time to resuscitation >2 hours 2
• Development of jaundice, hepatic encephalopathy, or fulminant hepatic failure (77.78% of deaths) 2
• AST/ALT elevation >1000 IU/L 2
• Metabolic acidosis and refractory shock 2
• Multi-organ failure (17.17% incidence) 2

Long-Acting Anticoagulant Considerations

• Patients with large intentional ingestions of "superwarfarins" may require vitamin K therapy for weeks to months 1, 7
• One case required 800 mg/day of vitamin K₁ (160 tablets daily) for brodifacoum poisoning with INR reaching 189 7
• Compliance with high-dose oral vitamin K is problematic due to pill burden (60-160 tablets/day); consider more concentrated formulations or IV therapy 7
• Frequency and amount of subsequent vitamin K doses should be determined by PT/INR response and clinical condition 5

Regional Variations

• In Southern India, yellow phosphorus-containing rodenticides dominate (67.2% yellow phosphorus alone, 24% yellow phosphorus + zinc phosphide), which carry additional hepatotoxicity risk beyond coagulopathy 2
• Paste formulations account for 90.91% of exposures in some regions 2

Disposition Criteria

Safe for Discharge

• Normal PT/INR at 48-72 hours post-exposure 1
• No clinical signs of bleeding 1
• Reliable follow-up available for repeat INR monitoring if indicated 7

Requires Continued ICU Care

• Any elevation in PT/INR requiring treatment 1
• Active bleeding or signs of organ dysfunction 2
• Development of hepatotoxicity, metabolic acidosis, or shock 2
• Large intentional ingestion requiring prolonged monitoring 1, 7