Rat Poisoning (Rodenticide Toxicology)

1. Anticoagulant Rodenticides

First Generation - Warfarin

• Mechanism: Inhibits Vitamin K epoxide reductase - blocks synthesis of factors II, VII, IX, X (and proteins C and S)
• Clinical: Significant coagulopathy requires large single doses or repeated exposures. Onset of anticoagulant effect: 12-48 hours. Half-life: ~42 hours
• Treatment:
  • Single small ingestion in children: no treatment necessary
  • Potentially toxic ingestion: activated charcoal
  • Monitor INR at baseline, 12-24 hours
  • Vitamin K1 (phytonadione) if INR >2.0: children 1-5 mg/day PO; adults 20 mg/day PO in 2-4 divided doses

Second Generation - Superwarfarins (Brodifacoum, Difenacoum, Bromadiolone)

• Mechanism: Same as warfarin, but far more potent and prolonged
• Half-life of brodifacoum: ~120 days - a single ingestion can cause anticoagulation for weeks to months
• Clinical: Coagulopathy within 24-48 hours of intentional ingestion; unexplained bleeding/coagulopathy should raise suspicion (patient may not disclose ingestion)
• Key point: NOT detected by warfarin assays - specific reference lab serum assays are required
• Treatment:
  • Acute intentional ingestion: gastric lavage (if early) + activated charcoal
  • Baseline INR, repeat at 12 and 24 hours
  • If INR elevated but no active hemorrhage: oral Vitamin K1 at high doses (50-100 mg/day or more in adults), continued for weeks to months due to long half-life
  • Active hemorrhage: FFP or PCC + IV Vitamin K1
  • Pediatric accidental ingestions are unlikely to cause significant toxicity; monitor INR at 24 and 48 hours

Also include indandiones (diphacinone, chlorophacinone): similar mechanism and clinical profile to superwarfarins.

2. Non-Anticoagulant Rodenticides

Aluminum Phosphide (ALP) / Zinc Phosphide

• Mechanism: Releases phosphine gas (PH3) on contact with moisture/gastric acid - a mitochondrial toxin inhibiting cytochrome c oxidase
• Odor: Garlic-like smell from mouth, gastric contents (forensically significant)
• Fatal dose ALP: 1-3 g (1-3 tablets); fatal period typically 6-12 hours; mortality 35-100%
• Zinc phosphide: Similar but slower onset due to gradual phosphine release
• Clinical features by severity:

• Most common cause of death: Cardiogenic shock
• Treatment (no specific antidote):
  1. Gastric lavage with potassium permanganate (after endotracheal intubation) - oxidizes phosphine to non-toxic phosphate; repeat 2-3 times
  2. Activated charcoal 100g with sorbitol (not water)
  3. Antacids - reduce gastric phosphine absorption
  4. Liquid paraffin - aids gut excretion
  5. Magnesium sulphate IV - reduces organ toxicity, corrects hypomagnesemia and arrhythmias (1g IV, repeated q2h, then 1-1.5g q6h for 5-7 days)
  6. Aggressive IV fluids: 4-6L in first 3-6 hours (50% normal saline)
  7. Low-dose dopamine 4-6 mcg/kg/min
  8. IV hydrocortisone 400 mg q4-6h
  9. Oxygen for hypoxia; sodium bicarbonate for metabolic acidosis
  10. Peritoneal dialysis/hemodialysis if renal failure
• Postmortem: Garlic odor, blood-stained froth, congested GI mucosa, centrizonal hemorrhagic necrosis of liver

Rodenticide poisoning impacts predators, scavengers, and pets through the food chain (The Essentials of Forensic Medicine and Toxicology, 36th ed.)

Strychnine

• Mechanism: Competitive antagonist of glycine at postsynaptic spinal cord and brainstem motor neurons
• Fatal dose: 50-100 mg (oral); 1-3g of Strychnos seeds
• Clinical:
  • Painful muscle spasms, opisthotonos, trismus ("risus sardonicus"/sardonic smile)
  • Mydriasis, proptosis
  • Patient remains conscious between convulsive episodes (key distinguishing feature)
  • Death from respiratory failure
• Differential diagnosis: Must be distinguished from tetanus, rabies, meningitis, cocaine toxicity
• Key difference from tetanus: History of poisoning vs. wound; no trismus prodrome; no autonomic instability

• Treatment:
  1. Airway control first
  2. Minimize sensory stimulation (quiet, dark room)
  3. Activated charcoal (within ~1 hour of ingestion)
  4. Avoid gastric lavage - may precipitate convulsions
  5. Diazepam IV 10-15 mg (adults), 0.1-0.3 mg/kg (children) for seizures
  6. Midazolam 5-10 mg; phenobarbitone 10 mg/kg if benzodiazepines insufficient
  7. Intubation + mechanical ventilation if needed
  8. Neuromuscular blockade (succinylcholine then non-depolarizing agents) if hyperthermia persists
  9. IV sodium bicarbonate for acidosis; dantrolene for refractory hyperthermia

Barium Carbonate

• Mechanism: Blocks potassium channels - causes severe hypokalemia
• Clinical: Onset within ~8 hours; severe vomiting, diarrhea, abdominal pain, muscle weakness, paralysis, cardiac dysrhythmias, respiratory failure
• Treatment: Activated charcoal + sodium/magnesium sulfate added to lavage (converts barium carbonate to less soluble barium sulfate); aggressive potassium replacement

Sodium Fluoroacetate (Compound 1080)

• Mechanism: Blocks the Krebs cycle (fluoroacetate → fluorocitrate → inhibits aconitase)
• Clinical: Nausea, vomiting, respiratory distress, lactic acidosis, seizures, coma, cardiac dysrhythmias, ventricular tachycardia/fibrillation, hypocalcemia, hyperkalemia
• Treatment: Activated charcoal; seizure and dysrhythmia control; glycerol monoacetate, calcium gluconate, sodium succinate, ethanol loading (experimental); toxicologist consultation required

Thallium

• Route of use: Formerly a common rodenticide (now largely banned)
• Mechanism: Mimics potassium, inhibits cellular enzymes
• Classic triad: Alopecia (2-3 weeks post-exposure), painful peripheral neuropathy, gastrointestinal illness
• Treatment: Prussian blue (ferric ferrocyanide) to bind thallium in the gut

Arsenic

• Clinical: Cholera-like diarrhea followed weeks-months later by peripheral neuropathy, Mees' lines (nail changes), skin changes (hyperpigmentation, keratosis)
• Treatment: Chelation with succimer (DMSA) or dimercaprol (BAL)

Yellow/White Phosphorus

• Clinical: Skin/oral burns, luminescent vomitus ("smoking stool syndrome"), garlic odor, direct cardiotoxicity, nephrotoxicity, late multiorgan failure with hepatorenal dysfunction
• Treatment: Supportive; cardiac monitoring; electrolyte correction; maintain serum glucose

Tetramine (TETS / Tetramethylenedisulfotetramine)

• Mechanism: Blocks GABA-A receptors in the CNS
• Clinical: Rapid onset - headache, nausea, dizziness, then loss of consciousness, refractory seizures, death (respiratory failure)
• Highly toxic: ~6-7 mg sufficient to kill an adult
• No antidote; treat with benzodiazepines/barbiturates for seizures

Summary Table

• The Essentials of Forensic Medicine and Toxicology, 36th Ed. (2026)
• Tintinalli's Emergency Medicine
• Parikh's Textbook of Medical Jurisprudence, Forensic Medicine and Toxicology
• Brenner and Rector's The Kidney

Xylocard (Lignocaine / Lidocaine)

Drug Profile

Mechanism of Action

• Binds preferentially to inactivated Na+ channels - greater effect on rapidly firing (ischemic/arrhythmic) tissue
• Shortens the action potential duration and effective refractory period in the His-Purkinje system and ventricular myocardium
• Suppresses automaticity - reduces spontaneous phase 4 depolarization in ectopic foci
• No significant effect on normal conduction - does not significantly slow AV conduction or sinus rate at therapeutic doses
• Little effect on atrial tissue - hence useless for atrial arrhythmias
• Minimal effect on the surface ECG at therapeutic doses - no significant change in PR interval, QRS width, or QT interval (unlike Class IA agents)

Indications (Cardiac - Antiarrhythmic Use)

1. Ventricular tachycardia (VT) - hemodynamically stable VT
2. Ventricular fibrillation (VF) - refractory VF/pulseless VT (second-line after amiodarone, or when amiodarone unavailable)
3. Ventricular ectopics - suppression of ventricular premature beats in specific contexts (e.g., after MI with frequent PVCs causing hemodynamic compromise)
4. Post-ROSC VF/pulseless VT - maintenance infusion may be considered after return of spontaneous circulation
5. Digitalis-induced arrhythmias - lidocaine or phenytoin preferred when AV block is present

Note: The 2015 AHA/ACLS guidelines removed lidocaine from the routine cardiac arrest algorithm. A 2016 multicenter RCT (ALPS trial) showed no improvement in survival or neurologic outcome with lidocaine (or amiodarone) vs. placebo for out-of-hospital cardiac arrest (OHCA) from VF/pulseless VT. Lidocaine remains an option when amiodarone is unavailable.

Dosing

Acute Arrhythmia (IV bolus)

• Loading dose: 1-1.5 mg/kg IV bolus (typically 75-100 mg in an adult)
• Repeat bolus: 0.5-0.75 mg/kg IV if arrhythmia persists, after 5-10 minutes
• Maximum total bolus dose: 3 mg/kg

Maintenance Infusion (post-conversion)

• Usual rate: 1-4 mg/min IV infusion
• If arrhythmia recurs during infusion: give additional 0.5 mg/kg bolus and increase infusion rate up to 4 mg/min

Dose Adjustments (CRITICAL)

• Liver disease (hepatically metabolized): same bolus, reduce infusion rate by 50%
• Age >70 years: same bolus, reduce infusion rate by 50%
• Heart failure/low cardiac output: reduce both bolus and infusion (reduced hepatic blood flow slows clearance)

Pharmacokinetics

Toxicity

CNS Toxicity (dose-dependent, early warning signs precede cardiac toxicity)

• Perioral/tongue numbness and tingling (paresthesia) - earliest sign
• Dizziness, drowsiness, tinnitus, reduced hearing
• Disorientation, confusion
• Muscle tremors
• Seizures (at high doses)

Cardiovascular Toxicity (higher doses)

• Myocardial depression
• Hypotension
• Widening QRS complex
• Bradycardia, AV block
• Circulatory collapse

Key point: CNS toxicity (perioral paresthesia, tremors) is the early warning - always precedes cardiac toxicity at typical doses. If a patient on a lidocaine infusion develops these symptoms, stop or reduce the infusion immediately.

Contraindications

• High-degree AV block (2nd or 3rd degree) without a pacemaker
• Sinoatrial block
• Stokes-Adams syndrome
• Severe sinus bradycardia
• Known hypersensitivity to amide-type local anesthetics
• Wolff-Parkinson-White (WPW) syndrome with SVT - may accelerate conduction through accessory pathway
• Atrial arrhythmias - ineffective (no significant effect on atrial tissue)

Important Drug Interactions

• Beta-blockers / cimetidine: Reduce hepatic clearance of lidocaine - increase toxicity risk
• Phenytoin (IV): Additive cardiac depression
• Procainamide: Additive CNS/cardiac toxicity
• Succinylcholine: Lidocaine prolongs its effect

Comparison: Lidocaine vs. Amiodarone in VT/VF

Other Uses of Lignocaine

• Local anesthetic for infiltration, nerve blocks, epidural, spinal anesthesia
• Topical anesthetic (viscous lignocaine for oropharyngeal procedures)
• IV lignocaine infusion for perioperative analgesia (reduces opioid requirements - systemic anti-inflammatory and analgesic effects)
• Intubation - IV bolus before laryngoscopy to blunt the hemodynamic response and reduce ICP surge

• Tintinalli's Emergency Medicine (Lidocaine/Lignocaine section, p. 200)
• Harrison's Principles of Internal Medicine 22E (2025)
• Goldman-Cecil Medicine
• Fischer's Mastery of Surgery

Ventricular Tachycardia (VT) - Treatment

Step 1: Immediate Risk Stratification

VT
├── Pulseless VT  →  Treat as VF (defibrillation + ACLS)
└── VT with pulse
        ├── Hemodynamically UNSTABLE  →  Immediate synchronized cardioversion
        └── Hemodynamically STABLE    →  Pharmacologic treatment

• Hypotension (SBP <90 mmHg)
• Altered mental status / loss of consciousness
• Acute chest pain / ischemia
• Signs of pulmonary edema / acute heart failure
• Shock

Step 2: VT Classification Matters

A. Pulseless VT - Treat as VF

1. CPR - High-quality, uninterrupted chest compressions
2. Defibrillation - Immediate unsynchronized shock
   • Biphasic: 120-200 J (manufacturer-recommended)
   • Monophasic: 360 J
3. Epinephrine 1 mg IV/IO every 3-5 minutes
4. Antiarrhythmics (after 2nd failed shock):
   • Amiodarone (first-line): 300 mg IV bolus; repeat 150 mg if no response
   • Lidocaine (alternative if amiodarone unavailable): 1-1.5 mg/kg IV bolus
5. Continue 2-minute CPR cycles with rhythm checks
6. Treat reversible causes (5 Hs and 5 Ts)

Note: A 2016 multicenter RCT (ALPS trial) showed neither amiodarone nor lidocaine improved survival to discharge or neurological outcomes vs. placebo for OHCA from VF/pulseless VT. However, both are still guideline options.

B. Hemodynamically UNSTABLE VT (with pulse)

• Sedate if possible (midazolam, etomidate, or ketamine)
• Energy: 100-200 J biphasic (synchronized mode); if fails, escalate
• After cardioversion: start IV antiarrhythmic infusion to prevent recurrence
• Critical: Always use SYNCHRONIZED mode to avoid R-on-T and VF induction
• Exception: If the QRS is very wide/bizarre and sync fails to lock - use unsynchronized

C. Hemodynamically STABLE Monomorphic VT

Treatment of stable wide-complex tachycardia - Tintinalli's Emergency Medicine

Drug Options (in order of preference):

• Dose: 20-50 mg/min IV (or 100 mg every 5 min) until:
  • Arrhythmia terminates, OR
  • QRS widens by >50%, OR
  • Hypotension occurs, OR
  • Maximum dose reached (17 mg/kg)
• Maintenance: 1-4 mg/min infusion
• Also useful when rhythm is uncertain (works for VT AND AF/SVT)
• Evidence: Recent study showed superiority of procainamide over amiodarone for conversion of stable VT
• Caution: Avoid in acute MI and LV dysfunction

• Dose: 150 mg in 100 mL D5W IV over 10 minutes
• Followed by: 1 mg/min infusion for 6 hours, then 0.5 mg/min for 18 hours
• Breakthrough: Additional 150 mg boluses over 10 min
• Maximum daily dose: 2.2 g
• Preferred over procainamide in setting of acute MI or reduced EF
• Also covers SVT with aberrancy if uncertain rhythm

• Loading: 50-100 mg IV over 2-3 min; may repeat in 5 min
• Maintenance: 1-4 mg/min infusion
• Reduce infusion by 50% in liver disease or age >70
• Less effective than procainamide or amiodarone for stable VT

D. Torsades de Pointes (Polymorphic VT + Long QT)

E. Polymorphic VT with Normal QT Interval

• Treat the underlying ischemia (urgent revascularization)
• IV beta-blockers
• IV amiodarone
• Prepare for synchronized cardioversion if unstable

Summary Drug Dosing Table

F. Long-Term / Definitive Management

1. ICD (Implantable Cardioverter-Defibrillator) - mainstay for secondary prevention and in patients with reduced EF (EF <35%) and sustained VT. Guideline class I indication for most patients with structural heart disease and sustained VT/VF
2. Catheter ablation - curative for idiopathic VTs (e.g., RVOT tachycardia, fascicular VT); palliative for scar-related VT causing frequent ICD shocks. Preferred over long-term antiarrhythmics for idiopathic VT
3. Oral antiarrhythmics - amiodarone, sotalol, mexiletine (as ICD adjuncts to reduce VT burden)
4. Beta-blockers - reduce VT recurrence, especially post-MI; also reduce appropriate ICD shocks
5. Treat underlying cause - revascularize ischemia, optimize heart failure, correct electrolytes, stop offending drugs

Key Clinical Pearls

• "When in doubt, treat as VT" - wide-complex regular tachycardia with history of heart disease is VT until proven otherwise
• Adenosine will NOT terminate VT - it helps diagnose/treat SVT with aberrancy; useful diagnostically
• Calcium channel blockers and beta-blockers are DANGEROUS in VT - may cause hemodynamic collapse
• Procainamide is safer than adenosine when rhythm is uncertain (wide-complex, unsure VT vs SVT) - it works for both
• Torsades requires magnesium, not amiodarone - amiodarone further prolongs QT
• Electrical storm (≥3 VT/VF episodes in 24h): IV beta-blockers (esmolol) + amiodarone + consider urgent ablation

• Tintinalli's Emergency Medicine (Chapters 18, 23)
• Sabiston Textbook of Surgery
• Goldman-Cecil Medicine
• The Washington Manual of Medical Therapeutics
• Harrison's Principles of Internal Medicine 22E (2025)