Organophosphate Poisoning

Mechanism of toxicity
Toxic dose
Symptoms and signs of poisoning
Special investigations
Management

Mechanism of toxicity

Irreversible inhibition of acetylcholinesterase which results in accumulation of acetylcholine (neurotransmitter) at synapses in the brain, autonomic nervous system (muscarinic receptors) and skeletal muscle (nicotinic receptors).

Toxic dose

Depends on substance.

Symptoms and signs of poisoning

Symptoms and signs may appear from within minutes up to 12 hours (rarely longer), after exposure.

• Muscarinic effects: hypersecretion (increased sweating, salivation and bronchial secretions), constricted pupils, bradycardia and hypotension, bronchoconstriction, vomiting, diarrhoea and urinary incontinence.
• Nicotinic effects: muscular weakness, fasciculations and weakness of respiratory muscles.
• CNS effects: restlessness, anxiety, headaches, convulsions, difficulty breathing and coma.

Special investigations

• Plasma or red cell cholinesterase activity: usually reduced by 50–90% of normal range (3000–8500 U/L in adults)

Management

Antidotes:

Muscarinic effects: atropine

• Indication: pulmonary symptoms (cause of death)
• Dose: initial IV test dose of 1 mg in adults provides a measure of severity, followed by 2–4 mg every 15 minutes until full atropinisation is achieved. Maintenance therapy: continuous IV infusion of 0.05 mg/kg/hour.
• The criterion of adequate therapy is control of excessive bronchial and oral secretions.
• As the patient improves, reduce the dose of atropine slowly, over 24 hours or longer.

Nicotinic effects: obidoxime (cholinesterase re activator)

• • Indication: consider in severe organophosphate poisoning. Value doubtful if started ≥ 24 h after exposure.
• • Contraindicated: Carbamate poisoning.
• • Dose: start about 5 minutes after the first dose of atropine. IV or IM, initially 250 mg (3–5 mg/kg). If a satisfactory response is obtained after the first dose, a further dose should be given once or twice at intervals of 2 h.

Symptomatic and supportive:

• Seizures: IV benzodiazepines
• Bronchospasm: inhaled ipatropium
• Hypotension: IV fluids, dopamine, noradrenaline

Monitoring:

• Muscarinic effects: hypersecretion, pupil size
• Cardiovascular: ECG , blood pressure and heart rate
• Pulmonary function: vital capacity
• Plasma cholinesterase concentrations