Organophosphate toxicity

Background

  • Organophosphates (OPs) found in:
    • Pesticides (e.g. malathion, parathion, chlorpyrifos, diazinon)
    • Chemical weapons / nerve agents (e.g. sarin, soman, tabun, VX, novichok)
    • Medications (e.g. echothiophate, neostigmine, edrophonium)
  • Highly lipid soluble; absorbed via dermal, gastrointestinal, or respiratory routes
  • Generally colorless, odorless, low volatility, and high lipophilicity
    • Some formulations have a garlic or petroleum-like odor (important clinical clue)[1]
  • These compounds act as Acetylcholinesterase inhibitors
    • Irreversibly bind and inhibit acetylcholinesterase (AChE), resulting in excess accumulation of acetylcholine at muscarinic receptors, nicotinic receptors (including the NMJ), and in the CNS → cholinergic toxicity[1]
    • This binding undergoes aging (dealkylation), which makes the enzyme permanently inactivated and resistant to reactivation by oximes (see below)

Organophosphates vs Carbamates

  • Carbamate poisoning (e.g. aldicarb, carbaryl, physostigmine) produces an identical cholinergic toxidrome
  • Key difference: carbamates reversibly inhibit AChE → shorter duration, spontaneous recovery
  • Carbamates do not undergo aging → pralidoxime is generally not needed (and its role is controversial)[2]
  • Carbamate toxicity is typically less severe and shorter-lasting[3]

Aging and Oxime Window

  • After OPs bind AChE, a secondary aging reaction (dealkylation) occurs, making the bond permanent and unresponsive to oxime therapy[4]
  • Aging half-life varies dramatically by compound:
Compound Type Aging Half-Life
Soman Nerve agent ~2-6 minutes
Sarin Nerve agent ~3 hours
Malathion Dimethyl pesticide ~3.7 hours
Tabun Nerve agent ~19 hours
Parathion Diethyl pesticide ~33 hours
VR Nerve agent ~139 hours

[5]

  • Clinical pearl: Dimethyl OPs (e.g. malathion) age rapidly → oximes must be given early. Diethyl OPs (e.g. parathion) age slowly → oxime therapy may be effective for longer[6]
  • If pralidoxime is given after aging is complete, it may paradoxically worsen toxicity (pralidoxime itself competitively inhibits AChE)[7]

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)

Household, Environmental, and Occupational Toxins

Clinical Features

  • Onset of symptoms varies from minutes (inhalation/nerve agents) to hours (dermal/ingestion) depending on route and agent
  • Symptoms caused by acetylcholine buildup at muscarinic receptors, nicotinic receptors, and in the CNS

CNS Effects

Muscarinic Effects

  • SLUDGE(M) = Salivation, Lacrimation, Urination, Diarrhea, GI pain, Emesis, Miosis
  • DUMBELLS = Diarrhea/Diaphoresis, Urination, Miosis, Bradycardia/Bronchorrhea, Emesis, Lacrimation, Lethargic, Salivation

Nicotinic Effects (NMJ)

  • MTWThF (days of week) = Mydriasis/Muscle cramps, Tachycardia, Weakness, Twitching, Hypertension/Hyperglycemia, Fasciculations
  • Note: Nicotinic stimulation can cause mydriasis and tachycardia, which may mask the classic muscarinic findings of miosis and bradycardia — do not use these alone to rule out OP poisoning[1]

Common Causes of Death

  • Killer B's = Bradycardia, Bronchorrhea, Bronchospasm
  • Respiratory failure is the primary cause of death: combination of bronchospasm, bronchorrhea, central respiratory depression, and diaphragmatic weakness[8]

Intermediate Syndrome

  • Occurs 24-96 hours after acute cholinergic crisis, typically after resolution of the acute cholinergic phase
  • Characterized by weakness of proximal limb muscles, neck flexors, and cranial nerve palsies
    • Clinical pearl: Earliest sign is often inability to lift the head from the pillow (neck flexor weakness) — a useful bedside test to detect impending respiratory failure[9]
  • Respiratory muscles may be affected → respiratory failure requiring mechanical ventilation
  • Can last for days to weeks
  • Thought to result from prolonged NMJ dysfunction due to sustained cholinergic overstimulation
  • Pralidoxime and atropine do NOT prevent or treat the intermediate syndrome[10][11]

Organophosphate-Induced Delayed Neuropathy (OPIDN)

  • Also called Type III syndrome or organophosphate-induced delayed polyneuropathy (OPIDP)
  • Rare; onset 1-5 weeks after acute exposure[12]
  • Distal sensorimotor axonopathy: paresthesias in stocking-glove distribution → ascending symmetric motor weakness → foot drop, wrist drop
  • Not related to AChE inhibition; thought to involve inhibition of neuropathy target esterase (NTE)[13]
  • No specific treatment; pralidoxime and atropine do not prevent OPIDN
  • Recovery is often incomplete — sensory symptoms may improve but motor deficits can be permanent[12]
  • Historical example: "Ginger Jake paralysis" in 1930s Prohibition-era USA (tri-ortho-cresyl phosphate contamination)
  • Key differential: Guillain-Barré syndrome (can mimic OPIDN; check history of OP exposure)

Differential Diagnosis

SLUDGE Syndrome

Weakness

Chemical weapons

Symptomatic bradycardia

Evaluation

Work-up

  • Point-of-care glucose — hyperglycemia may be present (nicotinic effect); hypoglycemia must be excluded in altered patients
  • CBC
  • Comprehensive Metabolic Panel
  • Lipase — pancreatitis has been reported as a complication[1]
  • VBG/ABG — assess for respiratory failure and acidosis
  • CXR
  • ECG

Diagnosis

  • Clinical diagnosis based on history and cholinergic toxidrome
  • Garlic or petroleum-like odor on patient's breath or clothing may be a clue
  • RBC acetylcholinesterase and plasma butyrylcholinesterase (pseudocholinesterase) levels:
    • Can confirm exposure but results are rarely available in time to guide acute management
    • RBC AChE is more specific for OP poisoning; plasma cholinesterase is more sensitive but less specific
    • Useful for confirmation, medicolegal documentation, and monitoring recovery
  • Peradeniya Organophosphorus Poisoning (POP) scale can be used to grade severity[1]

Management

Decontamination

  • Staff safety first: Don PPE before patient contact — nitrile or neoprene gloves (latex is insufficient), gown, eye protection[3]
  • Remove ALL clothing and bag separately; clothing can harbor residual OP
  • Wash skin thoroughly with soap and water
  • GI decontamination: Limited role
    • Activated charcoal: May be considered if within 1 hour of ingestion and airway is protected; limited evidence of benefit
    • Gastric lavage: Only if very early presentation (<1 hour) with large ingestion and protected airway[8]
    • Neither is routinely recommended due to rapid absorption and risk of aspiration

Antidotal Therapy

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[15]
  • 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[16]
  • Massive doses may be required — total doses of 100+ mg in the first 24 hours have been reported[17]
  • 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[18]
  • 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)[19]


Pralidoxime

  • AKA 2-PAM
  • Oxime that reactivates phosphorylated AChE → primarily reverses nicotinic symptoms (weakness, fasciculations, respiratory muscle paralysis)[20]
  • 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[21]
    • 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[22]
    • 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

Benzodiazepines

  • Diazepam or midazolam for seizures[1]
  • Diazepam 5-10 mg IV (pediatric: 0.2-0.5 mg/kg); repeat as needed
  • Prophylactic benzodiazepines may be considered in severe poisoning (especially nerve agent exposure)
  • Do NOT use phenytoin — ineffective for OP-induced seizures and may worsen toxicity[6]
  • Animal studies suggest benzodiazepines may also reduce OP-related brain injury

Supportive Care

  • Airway management: Early intubation for copious secretions, respiratory failure, or altered mental status
    • Avoid succinylcholine — metabolized by plasma cholinesterase (inhibited by OPs) → prolonged paralysis[1]
    • Use non-depolarizing agents (e.g. rocuronium) if RSI is needed; may require higher doses
  • IV fluid resuscitation for hypotension
  • Vasopressors if hypotension refractory to fluids
  • Continuous cardiac monitoring and pulse oximetry
  • Avoid: morphine, theophylline, aminophylline, phenothiazines, and reserpine (all potentiated by OPs or may worsen toxicity)[4]

Adjunctive Therapies (Emerging/Limited Evidence)

  • Magnesium sulfate: Some studies suggest benefit in reducing ICU stay, need for ventilation, and cardiac toxicity; insufficient evidence for routine use[23]
  • Sodium bicarbonate: Has been explored as adjunct; not yet standard of care[14]
  • Lipid emulsion therapy: Case reports only; not established
  • Fresh frozen plasma: Theoretical benefit (provides butyrylcholinesterase); limited evidence[14]

Disposition

  • Minimal exposure + completely asymptomatic for at least 6-12 hours after exposure → may be considered for discharge
    • Longer observation (up to 24 hours) for fat-soluble agents or large dermal exposures due to risk of delayed onset[8]
  • Admit all symptomatic patients — most will require ICU-level care
  • ICU admission criteria:
    • Need for atropine infusion
    • Respiratory distress or intubation
    • Hemodynamic instability
    • Seizures
    • Altered mental status
  • Monitor admitted patients for 48-96 hours for intermediate syndrome onset (watch for proximal weakness and neck flexor weakness)[9]
  • If evidence of deliberate self-harm → place on psychiatric hold and consult psychiatry
  • Poison control/toxicology consult for all significant exposures
  • If mass casualty or suspected nerve agent → activate HAZMAT response and notify public health authorities

Consultant Pearls

  • Toxicology: Call early for guidance on pralidoxime duration, atropine infusion management, and identification of the specific OP (dimethyl vs diethyl affects aging time)
  • ICU/Critical Care: Discuss need for mechanical ventilation and anticipate intermediate syndrome
  • Psychiatry: Mandatory for intentional ingestions
  • If EMS can identify the specific product/label: Bring it in — different OPs have different aging times, which directly impacts whether pralidoxime will be effective[6]


Medication Dosing

Antidotes

Adults

  • Atropine 1-2 mg IV, then double q5min as needed IV — Titrate to drying of secretions; massive doses may be required
  • Pralidoxime 1-2 g over 15-30 min, then 500 mg/hr infusion IV — Must give before aging occurs; continue until off ventilator

Pediatrics

  • Atropine 0.02-0.05 mg/kg (min 0.1 mg) IV — Double dose q5min until secretions dry
  • Pralidoxime 20-50 mg/kg, then 5-10 mg/kg/hr infusion IV

Seizures

See Also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Organophosphate Toxicity. StatPearls. NCBI Bookshelf. November 12, 2023. Accessed February 28, 2026.
  2. ↑ Eddleston M, et al. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371(9612):597-607. PMID 17706760
  3. ↑ 3.0 3.1 Organophosphate and Carbamate Poisoning (2024). International Emergency Medicine Education Project. December 26, 2024. Accessed February 28, 2026.
  4. ↑ 4.0 4.1 Pralidoxime. StatPearls. NCBI Bookshelf. May 1, 2023. Accessed February 28, 2026.
  5. ↑ Pralidoxime Is No Longer Fit for Purpose as an Antidote to Organophosphate Poisoning in the United Kingdom. Disaster Medicine and Public Health Preparedness. 2024.
  6. ↑ 6.0 6.1 6.2 Organophosphate Toxicity Treatment & Management. Medscape. Accessed February 28, 2026.
  7. ↑ How long is the window before ageing of acetylcholinesterase after organophosphate poisoning?. PharmaNUS. February 20, 2020. Accessed February 28, 2026.
  8. ↑ 8.0 8.1 8.2 8.3 Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. BMJ. 2007
    334(7594)
    629–634. doi:10.1136/bmj.39134.566979.BE. PMID 17379909. PMC 1839033.
  9. ↑ 9.0 9.1 Management of organophosphorus poisoning. World Federation of Societies of Anaesthesiologists. Accessed February 28, 2026.
  10. ↑ Roberts DM, Aaron CK. Management of acute organophosphorus pesticide poisoning. BMJ. 2007;334(7594):629-634. PMID 17379909
  11. ↑ Patel A, Chavan G, Nagpal AK. Navigating the Neurological Abyss: A Comprehensive Review of Organophosphate Poisoning Complications. Cureus. 2024
    16(2)
    e54329. doi:10.7759/cureus.54329.
  12. ↑ 12.0 12.1 Cholinesterase Inhibitors: Part 6: Organophosphate-Induced Delayed Neuropathy (OPIDN). ATSDR. CDC. Accessed February 28, 2026.
  13. ↑ Organophosphate-induced delayed neuropathy: A rare case report. Journal of Integrative Medicine and Research. 2024
    2(1)
    36–39. doi:10.4103/jimr.jimr_46_23.
  14. ↑ 14.0 14.1 14.2 Zoofaghari S, Maghami-Mehr A, Abdolrazaghnejad A. Organophosphate Poisoning: Review of Prognosis and Management. Advanced Biomedical Research. 2024
    13
    82. doi:10.4103/abr.abr_393_22. PMID 39568774. PMC 11542695.
  15. ↑ 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
  16. ↑ 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
  17. ↑ 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
  18. ↑ Mitra RL, Mohan S. Anaesthesia and organophosphorus poisoning. World Federation of Societies of Anaesthesiologists. Anaesthesia Tutorial of the Week. 2011.
  19. ↑ 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
  20. ↑ Bhatt MH, Bhatt S. Pralidoxime. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
  21. ↑ 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
  22. ↑ 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
  23. ↑ Organophosphate poisoning management: a review. Clinical and Experimental Emergency Medicine. 2025.
This page is issued from WikEM. The text is available under an unknown license unless otherwise noted. Additional terms may apply for the media files.