Discuss the mechanism, clinical features, investigations and management of organophosphate and other insecticide poisoning.

Introduction

Organophosphate (OP) compounds are the commonest cause of fatal poisoning in India, reflecting their free availability as agricultural insecticides. Common agents include malathion, parathion, dichlorvos, monocrotophos and chlorpyrifos. Exposure is usually deliberate self-poisoning by ingestion, less often occupational (dermal or inhalational) or accidental. Mortality remains high, driven by respiratory failure.

Mechanism

OP compounds irreversibly inhibit acetylcholinesterase by phosphorylating its active site. Acetylcholine therefore accumulates at:

• Muscarinic receptors — parasympathetic post-ganglionic synapses
• Nicotinic receptors — neuromuscular junction and autonomic ganglia
• Central nervous system synapses

"Ageing" is the key concept: over hours, the phosphorylated enzyme undergoes an irreversible conformational change and can no longer be reactivated by oximes. This is why pralidoxime must be given early — once ageing has occurred it is useless. Ageing time varies by compound, from minutes (some nerve agents) to 24–48 hours.

Carbamates (carbaryl, propoxur) inhibit cholinesterase reversibly and spontaneously hydrolyse within hours, producing a shorter, milder illness that does not require oximes.

Clinical Features

Nicotinic effects (mnemonic "MTWtHF" — Mydriasis, Tachycardia, Weakness, Hypertension, Fasciculations): muscle fasciculations, cramps, weakness, and ultimately paralysis including the diaphragm.

Central effects: anxiety, confusion, ataxia, convulsions, respiratory depression, coma.

Characteristic bedside clues: a garlic-like or kerosene odour of the breath and vomitus, pinpoint pupils, and copious secretions.

Three distinct phases:

1. Acute cholinergic crisis — minutes to hours after exposure, as described above.

2. Intermediate syndrome — 24–96 hours later, after apparent recovery. Weakness of proximal limb, neck flexor, cranial nerve and respiratory muscles, without fasciculations or cholinergic features. It does not respond to atropine or oximes, and requires mechanical ventilation — the commonest reason for unexpected deterioration on the ward.

3. OP-induced delayed polyneuropathy (OPIDN) — 2–3 weeks later; a distal sensorimotor axonopathy with foot drop and glove-and-stocking sensory loss, due to inhibition of neuropathy target esterase. Recovery is slow and often incomplete.

Investigations

• Red cell (true) acetylcholinesterase — correlates best with severity and with recovery.
• Plasma (pseudo)cholinesterase — falls earlier and is more widely available, but is less specific (also low in liver disease, malnutrition, pregnancy).
• Diagnosis is clinical; treatment must never await enzyme results.
• Arterial blood gas and continuous pulse oximetry; chest X-ray for aspiration pneumonitis and pulmonary oedema.
• ECG — bradycardia, QT prolongation, and risk of torsades de pointes and heart block.
• Electrolytes, blood glucose (hyperglycaemia is common), renal function, amylase (pancreatitis occurs), and creatine kinase.

Management

1. Resuscitation and decontamination

• Airway, breathing, circulation. Give high-flow oxygen. Aggressive suction of secretions. Intubate early for airway protection, copious secretions or weakness — do not wait for exhaustion.
• Remove all contaminated clothing and wash the skin with soap and water. Staff must wear gloves and aprons — secondary contamination of health workers is a real risk.
• Gastric lavage is of limited value and only if presentation is very early with a protected airway; activated charcoal may be given early. Do not induce emesis.

2. Atropine — the life-saving drug

• Antagonises muscarinic effects only; it does not reverse nicotinic weakness.
• Give as repeated doubling boluses until atropinisation is achieved, then maintain by infusion.
• Endpoints of atropinisation: clear chest on auscultation, drying of secretions, heart rate above 80/min, systolic BP above 80 mmHg. Pupils are a poor guide and dilate late.
• Watch for atropine toxicity — hyperthermia, agitation, delirium, absent bowel sounds, urinary retention — which can be mistaken for worsening poisoning.

3. Oximes (pralidoxime)

• Reactivate acetylcholinesterase by removing the phosphate group, and are the only agents that address nicotinic features and muscle weakness.
• Must be given as early as possible, before ageing occurs; given as a loading dose followed by continuous infusion.
• Not indicated in pure carbamate poisoning.

4. Supportive care

• Benzodiazepines for seizures and agitation; avoid succinylcholine for intubation (prolonged paralysis due to cholinesterase inhibition) — use a non-depolarising agent.
• Mechanical ventilation for respiratory failure and the intermediate syndrome, often for days to weeks.
• Fluid and electrolyte management; treat aspiration pneumonia; nutritional support.
• Observe for at least 48–96 hours even after apparent recovery, specifically watching for the intermediate syndrome.
• Psychiatric assessment before discharge in every case of deliberate self-poisoning, with risk assessment and follow-up.

Other Insecticides — Differentiation