Organophosphate toxicity

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  • Organophosphate nerve agent has been used as chemical weapon
  • Colorless, odorless, low volatility, and high lipophilicity
  • LD50 of 0.04mg/kg (10 mg). Death can occur within 15 minutes after absorption
  • Blocks acetylcholinesterase enzyme causing excess accumulation of acetylcholine at the neurojunction and cholinergic poisoning
  • Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes
  • Binds acetylcholinesterase → accumulation of acetylcholine at receptor sites → cholinergic crisis
  • Used as insecticides (malathion) and chemical warfare (sarin, VX)
  • Over 100 regularly used organophosphate compounds today.

Clinical Features

  • Symptoms caused by acetylcholine buildup in CNS and PNS.
  • CNS symptoms = headache, confusion, coma, vertigo
  • Muscarinic Receptors
    • SLUDGE(M) = Salivation, Lacrimation, Urination, Diarrhea, GI pain, Emesis, Miosis
  • Nicotinic Receptors (NMJ)
    • Muscle weakness, fasciculations, paralysis
  • Common causes of death in organophosphate toxicity
    • Killers B's = Bradycardia, Bronchorrhea, Bronchospasm

Intermediate Syndrome

  • Syndrome that occurs 24-96 hours after acute cholinergic crisis.
  • Proximal muscle weakness, cranial nerve palsies
  • Can last for days - weeks
  • May require mechanical ventilation

Differential Diagnosis


Chemical weapons

Symptomatic bradycardia



  • CBC
    • May show leukocytosis
  • Comprehensive Metabolic Panel
  • CXR
    • Pulmonary edema in severe cases
  • ECG
    • Ventricular dysrhythmias, torsades, QT prolongation, AV block


  • Clinical diagnosis
  • Blood tests such as RBC and plasma pseudocholinesterase levels are available, but little clinical utility



  • 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).


  • 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
    • DuoDate
      • Single autoinjector containing both medications
      • Same doses as Mark 1: atropine 2 mg + 2-PAM 600 mg



  • Competitively blocks muscarinic sites (does nothing for nicotinic-related muscle paralysis)
  • May require massive dosage (hundreds of milligrams)
  • Dosing[1]
  • Adult: Initial bolus of 2-6mg IV; titrate by doubling dose q5-30m until tracheobronchial secretions controlled
    • Once secretions controlled → start IV gtt 0.02-0.08 mg/kg/hr
    • Child: 0.05-0.1mg/kg (at least 0.1mg) IV; repeat bolus q2-30m until tracheobronchial secretions controlled
    • Once secretions controlled → start IV gtt 0.025 mg/kg/hr


  • AKA 2-PAM
  • For Organophosphate poisoning only - reactivates AChE by removing phosphate group → oxime-OP complex then excreted by kidneys.
    • This must be done before "aging" occurs - conformational change that makes OP bond to AChE irreversible.
  • Dosing[1]
    • Adult: 1-2gm IV over 15-30min; repeat in 1 hour if needed or 50 mg/hr infusion.
    • Child: 20-40mg/kg IV over 20min; repeat in 1 hour if needed or 10-20 mg/kg/hr infusion.


  • Minimal exposure + asymptomatic at least 12 hours after exposure can likely be discharged.
  • Admit all symptomatic patients!
  • If evidence of deliberate self harm, place on hold and consult psychiatry

See Also


  1. 1.0 1.1 Agency for Toxic Substances and Disease Registry, Case Studies in Environmental Medicine, Cholinesterase Inhibitors: Including Pesticides and Chemical Warfare Nerve Agents. Centers for Disease Control (CDC). PDF Accessed 06/21/15