Organophosphate Poisoning

What Are Organophosphates?

Mechanism of Toxicity

• Muscarinic receptors (parasympathetic effects - heart, smooth muscle, glands)
• Nicotinic receptors (neuromuscular junction and autonomic ganglia)
• Central nervous system receptors

Routes of Exposure

• Dermal (most common in agricultural settings - absorbed through skin)
• Ingestion (deliberate self-poisoning, a major cause of mortality in South/Southeast Asia)
• Inhalation (nerve agent warfare, fumigation accidents)
• Ocular (spray drift)

Clinical Features

Muscarinic Effects (the "SLUDGE" or "DUMBELS" mnemonics)

• Bronchospasm and bronchorrhea (most dangerous - the primary cause of death)
• Miosis (pinpoint pupils - highly characteristic)
• Bradycardia, hypotension
• Sweating

Nicotinic Effects (neuromuscular and ganglionic)

• Muscle fasciculations, twitching
• Weakness progressing to paralysis (including respiratory muscles)
• Tachycardia and hypertension (can mask or override the bradycardia)
• Pallor

CNS Effects

• Headache, anxiety, restlessness
• Seizures (common in severe poisoning)
• Coma
• Central respiratory depression

ECG Changes

• ST-segment changes, peaked T waves
• AV block, QT prolongation
• Torsades de pointes, ventricular tachycardia/fibrillation

The Three Phases / Syndromes

Diagnosis

1. History of exposure
2. Characteristic cholinergic toxidrome
3. Response to atropine (absence of anticholinergic signs after a full atropine dose is itself diagnostic)

• Red blood cell (RBC) AChE - more specific; reduced to 10-20% of normal in moderate, <10% in severe poisoning; takes up to 120 days to normalize after severe exposure
• Plasma pseudocholinesterase (butyrylcholinesterase) - more sensitive but less specific (decreased by liver disease, pregnancy, malnutrition, drugs); drops first after exposure; normalizes in 28-42 days
• Levels 30-50% of normal indicate exposure; toxic manifestations typically occur with >50% inhibition; symptoms may not appear until <20% of normal

Treatment

Step 1 - Decontamination (CRITICAL - protect healthcare workers)

• PPE mandatory: neoprene or nitrile gloves (not latex); treat all body fluids as contaminated
• Remove ALL clothing and accessories; bag as hazardous waste
• Wash patient with copious soap and water (scalp, hair, skin folds, fingernails, conjunctivae)
• Decontamination runoff water must be disposed of as hazardous material
• Do NOT transport by helicopter (risk of secondary exposure)

Step 2 - Supportive Care

• Airway - 100% O2 via non-rebreather mask; early endotracheal intubation for coma, seizures, respiratory failure, or severe bronchospasm/bronchorrhea
• Important: Use a non-depolarizing neuromuscular blocker if intubation needed - succinylcholine is metabolized by plasma butyrylcholinesterase and will cause prolonged paralysis
• Cardiac monitoring, pulse oximetry
• IV access with baseline cholinesterase levels
• Hypotension: isotonic crystalloid boluses
• Avoid: β-blockers, ester anesthetics (potentiate toxicity)

Step 3 - Antidotes

Atropine (Muscarinic Antagonist) - FIRST PRIORITY

• Adults: Initial bolus 1.2-3.0 mg IV (depending on severity); double the dose every 5 minutes until endpoints achieved
• Children: Start 0.05 mg/kg IV
• Endpoint of atropinization:
  • Chest clear on auscultation (bronchorrhea resolved) ← most important
  • Heart rate >80 bpm
  • Systolic BP >80 mmHg
  • Dry secretions
• NOT endpoints: pupillary dilatation; tachycardia is NOT a contraindication
• Massive ingestions may require hundreds of milligrams of atropine - contact pharmacy early
• Maintain with continuous infusion at 10-20% of the total loading dose per hour
• Absence of anticholinergic symptoms after initial atropine dose confirms OP poisoning

Pralidoxime (2-PAM) - Oxime/AChE Reactivator

• Give as early as possible; efficacy markedly decreases after 24-48 hours (aging)
• Indications include: respiratory depression/failure, fasciculations, seizures, dysrhythmias, hemodynamic instability, or large atropine requirements
• Combined autoinjector (Duodote / ATNNA): 600 mg pralidoxime + 2.1 mg atropine IM - used by emergency responders in field

Benzodiazepines

• Seizures: IV benzodiazepines (e.g., diazepam, lorazepam) - drug of choice

Step 4 - GI Decontamination

• Gastric lavage: No proven benefit; if considered (large ingestion within 1 hour), only after airway is secured - should NOT delay antidote administration
• Activated charcoal: No evidence of benefit on outcomes; not recommended routinely
• Hemodialysis/hemoperfusion: No proven value

Prognosis

• Death occurs through combined bronchorrhea, bronchospasm, respiratory muscle paralysis, and central apnea
• Intermediate syndrome carries additional risk of late respiratory death
• OPIDP (delayed neuropathy): recovery is variable; with TOCP poisoning, corticospinal signs may appear as the neuropathy resolves
• RBC AChE takes up to 120 days to fully recover after severe exposure

Recent Evidence Note

• Glycopyrrolate as an alternative to atropine (Rashid et al., 2025 - PMID: 38797902): systematic review evaluating efficacy and safety in OP and carbamate poisoning
• Umbrella review of therapeutic interventions (Chauhan et al., 2026 - PMID: 42258859): the most up-to-date synthesis of treatment evidence; may inform updates to pralidoxime recommendations, which have been debated in recent years