Organophosphate (OP) Poisoning

Mechanism

Clinical Features — The Cholinergic Toxidrome

Muscarinic Effects (Parasympathetic — "SLUDGE" + "Killer Bs")

Nicotinic Effects (NMJ + Sympathetic ganglia)

• Neuromuscular junction: Muscle fasciculations, weakness, paralysis, areflexia
• Sympathetic stimulation: Tachycardia, hypertension, mydriasis (may mask parasympathetic signs)

CNS Effects

• Anxiety, restlessness, tremor, headache, dizziness
• Confusion, delirium, hallucinations
• Seizures, coma

Death is most commonly due to respiratory failure — a combination of bronchorrhea, bronchospasm, and respiratory muscle paralysis.

Phases of Toxicity

Diagnosis

• Clinical diagnosis — do not wait for lab confirmation. History + cholinergic toxidrome is sufficient to initiate treatment.
• A characteristic garlic or hydrocarbon odor may be present.
• RBC cholinesterase (true AChE) and plasma pseudocholinesterase (butyrylcholinesterase) levels confirm exposure but are not needed to start treatment.
• EMG can identify AChE inhibition at neuromuscular junctions.

Management

1. Decontamination

• Remove and discard all clothing (dermal absorption is significant).
• Flush skin thoroughly with water (primary method); dry agents like flour, bentonite, or military resins are alternatives.
• Gastric lavage and activated charcoal are not beneficial — rapid GI absorption and profuse vomiting/diarrhea limit their utility.
• Caregivers must wear Level C PPE (full-face air-purifying mask, chemical-resistant suit, nitrile/butyl rubber gloves).

2. Stabilization & Supportive Care

• Airway is the priority — suction secretions, provide O₂, and initiate ventilatory support early.
• For RSI: prefer rocuronium 1 mg/kg over succinylcholine (succinylcholine is metabolized by cholinesterase and may have prolonged effect of 4–6 hours in OP poisoning).
• Benzodiazepines for seizures and agitation (after airway secured).
• Tachyarrhythmias — treat the underlying cholinergic excess, not with beta-blockers.
• No role for hemodialysis or enhanced elimination.

3. Antidote Therapy

Atropine (Muscarinic Blocker)

• First-line, competitive inhibitor of ACh at muscarinic receptors.
• Dose: 1–3 mg IV (0.05 mg/kg in children); double the dose every 5 minutes until muscarinic effects are controlled.
• Severely poisoned patients may require 200–500 mg in the first hour.
• Once stabilized, initiate infusion at 10–20% of total loading dose per hour.
• Endpoint: Drying of airway secretions, normalized respiratory rate, ease of breathing.
• ⚠️ Atropine does not reverse nicotinic effects (muscle paralysis).

Pralidoxime (2-PAM) — Oxime / AChE Reactivator

• Binds the OP–cholinesterase complex → conformational change → restores AChE function.
• Must be given early, before "aging" (irreversible covalent bonding) occurs.
• Indicated in moderate/severe poisoning: respiratory failure, fasciculations, seizures, dysrhythmias, large atropine requirements.
• Dose: 1–2 g IV (25–50 mg/kg pediatric) over 30 min, may repeat hourly; or 2 g over 20 min followed by 500 mg/h infusion for up to 7 days.
• Does not help the intermediate syndrome or delayed neuropathy.

Benzodiazepines

• For seizures and agitation: adequate dosing is required; do not under-treat.

Summary Treatment Table

Special Considerations

• Chemical warfare nerve agents (sarin, soman, VX): Extremely potent; death within minutes. Soman undergoes aging within minutes, leaving little time for oxime administration.
• Intermediate syndrome: Does not respond to atropine or pralidoxime — requires respiratory support.
• Children are at higher risk due to smaller body size and lower baseline cholinesterase activity.
• Chronic low-level exposure (farmworkers, exterminators): Subtle, nonspecific symptoms without the classic cholinergic syndrome.

Key Points

1. OP poisoning = irreversible AChE inhibition → ACh accumulation
2. Classic toxidrome: SLUDGE + Killer Bs + NMJ effects + CNS effects
3. Death = respiratory failure (bronchorrhea + muscle paralysis)
4. Antidotes: Atropine (titrate aggressively) + Pralidoxime (early, before aging)
5. Prefer rocuronium over succinylcholine for intubation
6. Intermediate syndrome occurs days later and does not respond to antidotes

Recent evidence: A 2025 systematic review (PMID 38797902) examined glycopyrrolate as an alternative anticholinergic in OP/carbamate poisoning — this may be relevant when atropine supplies are exhausted or in settings where atropine is scarce.