Organophosphate toxicity

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Background

  • 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 OP 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

Weakness

Chemical weapons

Symptomatic bradycardia

Evaluation

Work-up

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

Diagnosis

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

Management

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).

Antidotes

  • Atropine
    • 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
  • Pralidoxime
    • 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.

Disposition

  • 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

References

  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
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