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 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

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

  • Dosing with atropine and pralidoxime are time dependent and provides ability to reverse symptoms while awaiting agent metabolism


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