Organophosphate toxicity

Revision as of 20:38, 21 June 2015 by Mholtz (talk | contribs) (added intermediate syndrome (IMS))

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

  • Sx caused by acetylcholine buildup in CNS and PNS.
  • CNS Sx = 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

Diagnosis

Clinical diagnosis.

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

Work-up

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

Differential Diagnosis

Weakness

Chemical weapons

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
  • Benzodiazepines for seizures

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
  • No max dose, doses >400mg have been reported[2]

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[3]
    • 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 only requires decon and 6-8hr obs

See Also

References

  • World Health Organization. Environmental Health Criteria No 63. Organophosphorus Pesticides: A General Introduction. World Health Organization, Geneva 1986
  • Management of acute organophosphorus pesticide poisoning. Eddleston et al. Lancet. 2008 February 16; 371(9612): 597–607.
  • Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Milan Jokanovi´c, Toxicology Letters 190 (2009) 107–115
  • Tina Elersek and Metka Filipic (2011). Organophosphorous Pesticides - Mechanisms of Their Toxicity, Pesticides - The Impacts of Pesticides Exposure, Prof. Margarita Stoytcheva (Ed.), ISBN: 978-953-307-531-0, InTech, DOI: 10.5772/14020.
  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. Hopmann G, Wanke H. Höchstdosierte Atropinbehandlung bei schwerer Alkylphosphatvergiftung [Maximum dose atropin treatment in severe organophosphate poisoning (author's transl)]. Dtsch Med Wochenschr. 1974;99(42):2106-2108. doi:10.1055/s-0028-1108097
  3. 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.