Describe organophosphate poisoning and snake envenomation with their features and management.

Organophosphate Poisoning — Mechanism

Organophosphates phosphorylate the serine hydroxyl at the active site of acetylcholinesterase → The enzyme is irreversibly inhibited → acetylcholine accumulates at every cholinergic synapse → Over hours the phosphorylated enzyme undergoes "ageing" — loss of an alkyl group makes the bond permanent → Once aged, the enzyme can never be reactivated, and function returns only as new enzyme is synthesised over weeks → Hence pralidoxime must be given early, before ageing is complete

Clinical Features

Management of Organophosphate Poisoning

• Protect yourself, remove contaminated clothing and wash the skin thoroughly — absorption continues through skin
• Airway, high-flow oxygen, suction, and early intubation and ventilation where secretions or weakness threaten the airway
• Atropine — 2 to 5 mg intravenously, doubled every 5 minutes until the chest is clear, then an infusion; endpoints are dry secretions, clear lungs, heart rate above 80 and systolic pressure above 80 mmHg
• Pralidoxime (2-PAM) — reactivates cholinesterase by removing the phosphate group; effective only before ageing, so it is given as early as possible, 1 to 2 g intravenously then an infusion. It works chiefly on the nicotinic features that atropine does not touch
• Diazepam for agitation and seizures; it also reduces central toxicity and mortality
• Avoid succinylcholine if intubation is needed, since it is metabolised by the same inhibited enzyme and paralysis will be greatly prolonged
• Later complications — intermediate syndrome at 24 to 96 hours, with proximal and respiratory muscle weakness requiring ventilation; and organophosphate-induced delayed polyneuropathy at 2 to 3 weeks, from inhibition of neuropathy target esterase, which neither atropine nor pralidoxime prevents

Snake Envenomation

• The 20-minute whole blood clotting test (20WBCT) — fresh blood in a clean, dry glass tube, left undisturbed for 20 minutes. Failure to clot indicates coagulopathy and is an indication for antivenom. It requires no laboratory and is the single most useful bedside test in rural India
• First aid — reassure, immobilise the limb in a neutral position, and transport to hospital urgently. NO tourniquets, NO incision, NO suction, NO ice, NO electric shock, NO traditional remedies; all cause harm and delay
• Antivenom — polyvalent against the big four, given intravenously and repeated until the coagulopathy corrects or neurotoxicity reverses. It is indicated for systemic envenomation, not for a bite alone; a dry bite needs observation, not antivenom
• Anaphylactic reactions to antivenom are common — adrenaline must be drawn up and ready before the infusion starts; the reaction is treated and the antivenom continued, since the alternative is death from envenomation
• Neostigmine with atropine may reverse neurotoxicity in cobra bites, where the toxin is a competitive postsynaptic blocker; it is ineffective in krait envenomation, which is presynaptic and irreversible
• Ventilation is the definitive treatment for neurotoxic envenomation, and patients recover fully if respiration is supported until the toxin wears off

Other Common Poisonings in India

Scorpion Sting and Other Envenomation

• Scorpion sting — the Indian red scorpion (Mesobuthus tamulus) causes an autonomic storm: initial parasympathetic features (vomiting, sweating, bradycardia, priapism) followed by a massive sympathetic surge with hypertension, tachycardia, myocarditis and pulmonary oedema, which is the usual cause of death
• Prazosin is the treatment of choice — an alpha1 blocker that reduces preload and afterload and counters the catecholamine surge; it has markedly reduced mortality and is cheap and orally active. Scorpion antivenom is used in addition where available
• Beta-blockers are avoided, since unopposed alpha stimulation worsens the hypertension and pulmonary oedema
• Honey bee and wasp stings — local reactions are common; the danger is anaphylaxis, treated with intramuscular adrenaline. Multiple stings cause a toxic reaction with haemolysis, rhabdomyolysis and renal failure
• Spider bites — rarely serious in India; supportive care
• Tetanus prophylaxis is required after any bite or sting that breaks the skin, and is frequently forgotten in the urgency of treating the envenomation
• Most snake bites are by non-venomous species or are "dry", so antivenom is given for evidence of systemic envenomation rather than for the bite itself; unnecessary antivenom exposes the patient to anaphylaxis for no benefit

Applied Aspects

• Give atropine generously and titrate to the chest; the commonest error in organophosphate poisoning is giving too little for too short a time
• Watch for the intermediate syndrome after apparent recovery; patients have died after being stepped down from intensive care
• Keep antivenom and adrenaline together, and never give antivenom where resuscitation facilities are absent
• Snakebite is a neglected tropical disease with a large burden in India, and most deaths follow delay, traditional treatment and lack of antivenom in peripheral facilities rather than any failure of the drug
• Advise prevention — sleeping on a cot rather than the floor and using a torch at night prevent a large proportion of krait bites
• Restricting access to the most toxic pesticides has reduced suicide deaths in several countries more effectively than any improvement in treatment
• Do not use succinylcholine to intubate an organophosphate-poisoned patient; it is hydrolysed by the very enzyme that is inhibited, and paralysis may last hours
• Keep the pesticide container — the label identifies the compound and its concentration, and the management of an organophosphate differs entirely from that of aluminium phosphide or a pyrethroid
• Carbamates inhibit cholinesterase reversibly and do not undergo ageing, so they cause a shorter illness and pralidoxime is generally not needed
• Anticipate the need for prolonged ventilation in both severe organophosphate poisoning and neurotoxic envenomation; these patients recover fully if respiration is supported, and die if it is not
• Ask about the circumstances of the snake bite — a painless bite while sleeping on the floor at night, presenting with morning paralysis and abdominal pain, is characteristic of the krait and is frequently misdiagnosed