Pesticide-Related Neurotoxicity

Pesticide related neurotoxicity is nervous system injury from agricultural, public health or domestic pesticides. It covers acute cholinergic poisoning from organophosphates and carbamates, intermediate syndrome, seizures from organochlorines, paraesthesia from pyrethroids, and chronic cognitive, mood and movement disorders after long exposure.

Epidemiology. Pesticide self-poisoning and occupational poisoning cause hundreds of thousands of deaths each year worldwide, mostly in low and middle income regions. Farm workers, sprayers, greenhouse and horticultural workers and mixers are at highest risk.

Classes. Organophosphates and carbamates inhibit acetylcholinesterase. Organochlorines affect chloride channels and cause seizures. Pyrethroids prolong sodium channel opening. Paraquat and rotenone are linked with parkinsonism risk.

Phases. Acute cholinergic phase (minutes to hours), intermediate syndrome (1 to 4 days), delayed neuropathy (1 to 3 weeks, with some organophosphates), and chronic neuropsychiatric effects.

Pathophysiology.

Organophosphates phosphorylate acetylcholinesterase, and aging of the enzyme inhibitor complex makes inhibition irreversible. Accumulated acetylcholine overstimulates muscarinic and nicotinic receptors and the central nervous system.

Carbamates inhibit the enzyme reversibly and for shorter periods. Chronic effects are linked to repeated low level inhibition, oxidative stress and mitochondrial injury.

• Muscarinic: salivation, lacrimation, urination, diarrhoea, vomiting, bronchorrhoea, bronchospasm, bradycardia and miosis.
• Nicotinic: fasciculations, weakness and paralysis; tachycardia and hypertension.
• Central: agitation, confusion, seizures, coma and respiratory depression.
• Intermediate syndrome: proximal limb, neck flexor and respiratory muscle weakness with cranial nerve palsies.
• Chronic: impaired memory and attention, mood disorder, and increased risk of parkinsonism.

Red flags.

• Respiratory failure, bronchorrhoea or coma.
• Seizures, hypotension or arrhythmia.
• Neck flexor or respiratory muscle weakness 1 to 4 days after poisoning.

• History: agent, route, amount, timing and container; clinical cholinergic toxidrome is enough to start treatment.
• Red cell acetylcholinesterase and plasma butyrylcholinesterase: red cell activity reflects synaptic inhibition better, and a fall of 30% or more from the worker's baseline requires removal from exposure. Treatment must not wait for results.
• ECG (QTc prolongation, bradycardia), oxygen saturation, arterial gas, electrolytes, glucose, creatine kinase and amylase.
• Serial neck flexion strength and vital capacity to detect intermediate syndrome.
• Nerve conduction studies for delayed neuropathy; neuropsychological testing for chronic effects.

Differential diagnosis. Nicotine and other cholinergic poisoning, carbamate poisoning, sympathomimetic or anticholinergic toxicity, opioid toxicity, gastroenteritis, sepsis, status epilepticus of other cause, myasthenia gravis.

• Protect staff with gloves and gowns. Remove contaminated clothing and wash skin and hair thoroughly. Airway, oxygen and ventilation first, because atropine does not help a hypoxic patient.
• Atropine 1 to 3 mg intravenously as a bolus, then double the dose every 5 minutes until atropinisation (clear chest on auscultation, heart rate over 80 beats/min, systolic pressure over 80 mmHg, dry axillae and pupils no longer pinpoint). Then infuse 10 to 20% of the total loading dose each hour, titrated to these end points. Children: 0.05 mg/kg intravenously, doubled every 5 minutes. No fixed maximum. Monitor for atropine toxicity (delirium, hyperthermia, ileus, urinary retention) and reduce the infusion. Do not use heart rate alone for dosing. No renal adjustment.
• Pralidoxime chloride 30 mg/kg intravenously over 30 minutes, then 8 mg/kg/hour by infusion until atropine is no longer needed for 12 to 24 hours. Children use the same weight based regimen. Benefit is uncertain, and it is most useful early and with organophosphates that age slowly. Rapid injection causes laryngospasm and rigidity. It is renally cleared, so reduce the dose in renal impairment. Not needed for pure carbamate poisoning.
• Seizures or severe agitation: diazepam 10 mg intravenously over 2 minutes, repeated once after 10 minutes. Maximum 20 mg before specialist review. Monitor breathing and blood pressure; caution in respiratory depression and hepatic impairment.
• Activated charcoal 50 g orally within 1 hour of ingestion only when the airway is protected. Gastric lavage is not routine.
• Intermediate syndrome: ventilatory support until recovery.
• Organochlorine seizures: benzodiazepines; avoid oils and fats that increase absorption.
• Chronic neuropsychiatric effects: remove from exposure and give supportive care.

Monitoring. Heart rate, respiratory rate, secretions, pupils and muscle power every 15 minutes at first, then hourly; vital capacity and neck flexion strength every 4 to 6 hours for 4 days; cholinesterase recovery over weeks.

Referral and escalation. Intensive care for respiratory failure, intermediate syndrome or ongoing high atropine needs; toxicology advice for all significant poisoning; psychiatric review after deliberate self-poisoning; occupational physician for exposure and co-worker review; notification and compensation where required.

Special groups. Children need weight based atropine and early specialist input. Pregnancy: atropine and pralidoxime are used when needed because maternal survival comes first.