Organophosphate toxicity

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Background

  • Organophosphates found in:
  • Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes
  • Colorless, odorless, low volatility, and high lipophilicity
  • These compounds act as Acetylcholinesterase inhibitors
    • Block acetylcholinesterase, resulting in excess accumulation of acetylcholine at the neuromuscular junction and cholinergic toxicity
  • LD50 of 0.04mg/kg (10 mg). Death can occur within 15 minutes after absorption

Autonomic Nervous System Receptors and Their Effects

  • Parasympathetic - ACh is transm
    • Muscarinic
      • receptors in heart, eye, lung, GI, skin and sweat glands
      • Bradycardia
      • Miosis
      • Bronchorrhea / Bronchospasm
      • Hyperperistalsis (SLUDGE)
      • Sweating
      • Vasodilation
    • Nicotinic
  • Sympathetic
    • Alpha effects (vessels, eye, skin)
    • Beta effects (heart, lungs)

Clinical Features

  • Symptoms caused by acetylcholine buildup in CNS and PNS.
  • CNS symptoms = headache, confusion, vertigo, seizures, coma
  • Muscarinic Receptors
    • SLUDGE(M) = Salivation, Lacrimation, Urination, Diarrhea, GI pain, Emesis, Miosis
    • DUMBELLS = Diarrhea, diaphoresis, Urination, Miosis, Bradycardia, Bronchorrea, Emesis, Lacrimation, Lethargic, Salivation
  • Nicotinic Receptors (NMJ)
    • MTWThF (days of week) = Mydriasis/Muscle cramps, Tachycardia, Weakness, Twitching, Hypertension/Hyperglycemia, Fasciculations, Seizures, Somnolent
  • Common causes of death in organophosphate toxicity
    • Killers B's = Bradycardia, Bronchorrhea, Bronchospasm

Intermediate Syndrome

Differential Diagnosis

SLUDGE Syndrome

Weakness

Chemical weapons

Symptomatic bradycardia

Evaluation

Work-up

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)
    • Succinylcholine is absolutely contraindicated

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

  • 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[2]
    • Pralidoxime can actually bind and inhibit AChE once all AChE enzymes have aged, and can make the toxicity worse
    • Window to aging depends on the agent, and is a matter of debate, but pralidoxime within 1-2 hours of exposure is the goal
  • 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
  2. Eddleston M, Szinicz L, Eyer P, Buckley, N (2002) Oximes in Acute Organophosphate Pesticide Poisoning: a Systematic Review of Clinical Trials. QJM. 95(5): 275–283.

Authors:

Ross Donaldson