Organophosphate toxicity

Background

• Irreversibly binds acetylcholinesterase -> cholinergic crisis
• Used as insecticides (malathion) and chemical warfare (sarin, VX)
• Consider in ddx of pt w/ AMS + miotic pupils

Clinical Features

1. SLUDGE(MM)
   1. Salivation, lacrimation, urination, diarrhea, GI pain, emesis, miosis, muscle weakness
2. Killers B's
   1. Bradycardia, bronchorrhea, bronchospasm

Diagnosis

• CBC
  • May show leukocytosis
• Lipase
• LFT
• CXR
  • Pulmonary edema in severe cases
• ECG
  • Ventricular dysrhytmias, torsades, QT prolongation, AV block

Decontamination

• Providers should wear appropriate PPE during decontamination.
  • Neoprene or nitrile gloves and gown (latex and vinyl are ineffective)
• Dispose of all clothes in biohazard container
• Wash patient with soap and water

Supportive Care

• IVF, O2, Monitor
• Aggressive airway management is of utmost importance.
  • Intubation often needed due to significant respiratory secretions / bronchospasm.
  • Use nondepolarizing agent (Rocuronium or Vecuronium)
  • Succinylcholine is absolutely contraindicated
• Benzodiazepines for seizures

Antidotes

• Dosing with atropine and pralidoxime are time dependent and provides ability to reverse symptoms while awaiting agent metabolism
• For exposure to nerve agents, manufactured IM autoinjectors are available for rapid administration:
  • Mark 1
    • Contains 2 separate cartridges: atropine 2 mg + 2-PAM 600 mg
    • Being phased out with newer kits
  • DuoDote
    • Single autoinjector containing both medications
    • Same doses as Mark 1: atropine 2 mg + 2-PAM 600 mg

Antidotes

Atropine

• First-line antidote — muscarinic antagonist; treats bronchorrhea, bronchospasm, bradycardia, and secretions
• Does NOT reverse nicotinic symptoms (weakness, fasciculations, paralysis)
• Starting dose: Atropine 1-2 mg IV (double q5min until atropinization) IV — May need 100+ mg in first 24h; endpoint is drying of secretions
• Pediatric: Atropine 0.02-0.05 mg/kg IV (min 0.1 mg), double q5min IV
• Doubling protocol: If inadequate response after 5 minutes, double the dose (1 → 2 → 4 → 8 → 16 mg...) until atropinization is achieved
• Massive doses may be required — total doses of 100+ mg in the first 24 hours have been reported
• Endpoints of adequate atropinization (goal of therapy):
  • Drying of bronchial secretions (most important endpoint)
  • Heart rate >80 bpm
  • Systolic BP >80 mmHg
• Do NOT target: Fully dilated pupils, absent bowel sounds, or HR >150 — these indicate atropine toxicity
• After initial atropinization: Consider atropine infusion (10-20% of loading dose per hour) to maintain effect
• Optimize oxygenation before giving atropine to reduce risk of dysrhythmias (though in resource-limited settings, do not withhold atropine waiting for oxygen)

Pralidoxime

• AKA 2-PAM
• Oxime that reactivates phosphorylated AChE → primarily reverses nicotinic symptoms (weakness, fasciculations, respiratory muscle paralysis)
• Must give atropine BEFORE pralidoxime to prevent worsening of muscarinic symptoms
• Must be given before aging occurs (see aging table above)
• Pralidoxime 1-2 g IV over 15-30 min, then 8-10 mg/kg/hr infusion (or repeat bolus in 1 hr) IV
• Pediatric: Pralidoxime 20-50 mg/kg IV, then 5-10 mg/kg/hr infusion IV
• Continue until clinical improvement or patient is off ventilator
• Controversies:
  • Evidence for benefit of pralidoxime is inconsistent; several meta-analyses have not shown clear mortality benefit when added to atropine
  • However, per AHA 2023 guidelines and expert consensus, oximes should still be given for significant OP poisoning, particularly when fasciculations, weakness, or paralysis are present
  • Efficacy depends on timing (before aging), dose, and the specific OP compound involved
• Caution: Administer slowly — rapid IV push can cause hypertensive crisis, cardiac arrest

Disposition

• Minimal exposure only requires decon and 6-8hr obs

See Also

Toxidromes

Source

• Tintinalli