Organophosphate toxicity: Difference between revisions
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*[[Organophosphates]] found in:
*[[Organophosphates]] found in:
**Pesticides (e.g. malathion, diazinon)
**Pesticides (e.g. malathion, diazinon)
**[[Chemical weapons]] (e.g. Sarin,  nerve agents has been used as chemical weapon
**[[Chemical weapons]] (e.g. Sarin,  nerve agents has been used as chemical weapon)
**medications (e.g. [[neostigmine]], [[edrophonium]]
**medications (e.g. [[neostigmine]], [[edrophonium]]
*Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes
*Highly lipid soluble: absorbed via dermal, gastrointestinal or respiratory routes

Revision as of 22:24, 3 October 2023

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
  • 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

  • First-line antidote — muscarinic antagonist; treats bronchorrhea, bronchospasm, bradycardia, and secretions[1]
  • Does NOT reverse nicotinic symptoms (weakness, fasciculations, paralysis)
  • Starting dose: Atropine 1-2 mg IV (double q5min until atropinization) IV — May need 100+ mg in first 24h; endpoint is drying of secretions
  • Pediatric: Atropine 0.02-0.05 mg/kg IV (min 0.1 mg), double q5min IV
  • Doubling protocol: If inadequate response after 5 minutes, double the dose (1 → 2 → 4 → 8 → 16 mg...) until atropinization is achieved[2]
  • Massive doses may be required — total doses of 100+ mg in the first 24 hours have been reported[3]
  • Endpoints of adequate atropinization (goal of therapy):
    • Drying of bronchial secretions (most important endpoint)
    • Heart rate >80 bpm
    • Systolic BP >80 mmHg
  • Do NOT target: Fully dilated pupils, absent bowel sounds, or HR >150 — these indicate atropine toxicity[4]
  • After initial atropinization: Consider atropine infusion (10-20% of loading dose per hour) to maintain effect
  • Optimize oxygenation before giving atropine to reduce risk of dysrhythmias (though in resource-limited settings, do not withhold atropine waiting for oxygen)[5]


Pralidoxime

  • AKA 2-PAM
  • Oxime that reactivates phosphorylated AChE → primarily reverses nicotinic symptoms (weakness, fasciculations, respiratory muscle paralysis)[6]
  • Must give atropine BEFORE pralidoxime to prevent worsening of muscarinic symptoms
  • Must be given before aging occurs (see aging table above)
  • Pralidoxime 1-2 g IV over 15-30 min, then 8-10 mg/kg/hr infusion (or repeat bolus in 1 hr) IV
  • Pediatric: Pralidoxime 20-50 mg/kg IV, then 5-10 mg/kg/hr infusion IV
  • Continue until clinical improvement or patient is off ventilator
  • Controversies:
    • Evidence for benefit of pralidoxime is inconsistent; several meta-analyses have not shown clear mortality benefit when added to atropine[7]
    • However, per AHA 2023 guidelines and expert consensus, oximes should still be given for significant OP poisoning, particularly when fasciculations, weakness, or paralysis are present[8]
    • Efficacy depends on timing (before aging), dose, and the specific OP compound involved
  • Caution: Administer slowly — rapid IV push can cause hypertensive crisis, cardiac arrest

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. ↑ Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1
  2. ↑ Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1
  3. ↑ Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784
  4. ↑ Mitra RL, Mohan S. Anaesthesia and organophosphorus poisoning. World Federation of Societies of Anaesthesiologists. Anaesthesia Tutorial of the Week. 2011.
  5. ↑ Eddleston M, Chowdhury FR. Pharmacological treatment of organophosphorus insecticide poisoning: the old and the (possible) new. Br J Clin Pharmacol. 2016;81(3):462-470. doi:10.1111/bcp.12784
  6. ↑ Bhatt MH, Bhatt S. Pralidoxime. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
  7. ↑ Peter JV, Sudarsan TI, Moran JL. Clinical features of organophosphate poisoning: A review of different classification systems and approaches. Indian J Crit Care Med. 2014;18(11):735-745. doi:10.4103/0972-5229.144017
  8. ↑ Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. doi:10.1016/S0140-6736(07)61202-1
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