Organophosphate toxicity

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

• Neuromuscular weakness
  • UMN:
    • CVA
    • Hemorrhagic stroke
    • Multiple sclerosis
    • Amyotrophic Lateral Sclerosis (ALS) (UMN & LMN)
  • Spinal cord disease:
    • Infection (Epidural abscess)
    • Infarction/ischemia
    • Trauma (Spinal Cord Syndromes)
    • Inflammation (Transverse Myelitis)
    • Degenerative (Spinal muscular atrophy)
    • Tumor
  • Peripheral nerve disease:
    • Guillain-Barre syndrome
    • Toxins (Ciguatera)
    • Tick paralysis
    • DM neuropathy (non-emergent)
  • NMJ disease:
    • Myasthenia gravis crisis
    • Botulism
    • Organophosphate toxicity
    • Lambert-Eaton myasthenic syndrome
  • Muscle disease:
    • Rhabdomyolysis
    • Dermatomyositis
    • Polymyositis
    • Alcoholic myopathy
• Non-neuromuscular weakness
  • Can't miss diagnoses:
    • ACS
    • Arrhythmia/Syncope
    • severe infection/Sepsis
    • Hypoglycemia
    • Periodic paralysis (electrolyte disturbance, K, Mg, Ca)
      • Hypokalemic periodic paralysis
      • Thyrotoxic periodic paralysis
    • Respiratory failure
  • Emergent Diagnoses:
    • Symptomatic Anemia
    • Severe dehydration
    • Hypothyroidism
    • Polypharmacy
    • Malignancy
  • Other causes of weakness and paralysis
    • Acute intermittent porphyria (ascending weakness)

Chemical weapons

• Blister chemical agents (Vesicants)
  • Lewisite (L)
  • Sulfur mustard (H)
  • Phosgene oxime (CX)
• Pulmonary chemical agents
  • Ammonia
  • Methyl isocyanate
  • Methyl bromide
  • Hydrochloric acid
  • Chlorine gas
  • Phosgene
  • Pepper spray
• Incendiary agents
  • Agent orange
  • White phosphorus
• Cyanide chemical weapon agents
  • Hydrocyanic acid
  • Formonitrile
  • Prussic acid
• Nerve Agents
  • Acetylcholinesterase inhibitors
  • Includes household and commercial pesticides (diazinon and parathion)
  • G-series (sarin, tabun, soman) and V-series (VX)
  • V-series high viscosity with oily consistency

Symptomatic bradycardia

• Ischemia/Infarction
  • Inferior MI (involving RCA)
• Neurocardiogenic/reflex-mediated
  • Increased ICP
  • Vasovagal reflex
  • Hypersensitive carotid sinus syndrome
  • Intra-abdominal hemorrhage (i.e. ruptured ectopic)
• Metabolic/endocrine/environmental
  • Hyperkalemia
  • Hypothermia (Osborn waves on ECG)
  • Hypothyroidism
  • Hypoglycemia (neonates)
• Toxicologic
  • B-blocker
  • Ca-channel blocker
  • Digoxin toxicity
  • Opioids
  • Organophosphates
  • Clonidine
• Infectious/Postinfectious
  • Chagas disease
  • Lyme disease
  • Syphilis
• Sick Sinus Syndrome

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
    • 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
    • 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

• Toxidromes

References

Authors

Jordan Swartz, Michael Holtz, Ross Donaldson, Daniel Ostermayer, Aaron Snyder, Kian Preston-Suni, Abdus Salam Khan, Claire, Eunice Pae, Neil Young