The Drooling Farmer
A 40-year-old farmer is brought to the emergency department two hours after spraying an organophosphate insecticide in a closed greenhouse without a mask. He is drooling, tearing, sweating profusely, and passing urine involuntarily. His pupils are pinpoint and do not dilate to light; pulse 46/min; wheeze with coarse crepitations; he has twitching of the eyelids and calves that progress to generalised fasciculations followed by profound flaccid weakness. There is no history of trauma or fever. Plasma cholinesterase is 15% of normal; serum amylase is mildly raised. The intern gives atropine, and after 20 minutes the salivation, sweating and bradycardia improve, but the weakness remains and the fasciculations continue. A relative asks whether washing the skin is really necessary 'now that the antidote has been given'.
1. Trace the sequence from acetylcholinesterase inhibition to pinpoint pupils, bradycardia, salivation and muscle fasciculations. Name the receptor and the division of the nervous system at each site.
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Acetylcholinesterase normally hydrolyses acetylcholine within milliseconds of release. When it is inhibited, acetylcholine accumulates in every cholinergic synaptic cleft and the effect depends on which receptor is present.
- Pinpoint pupils: parasympathetic fibres travelling with the oculomotor nerve release acetylcholine onto M3 receptors of the constrictor pupillae, which contract. The sympathetic dilator is overwhelmed, so the pupil cannot dilate to light.
- Bradycardia: vagal postganglionic fibres release acetylcholine onto M2 receptors on the sinoatrial node, slowing the pacemaker.
- Salivation and tearing: parasympathetic M3 receptors on salivary and lacrimal glands produce copious watery secretion.
- Fasciculations: at the neuromuscular junction the receptor is nicotinic (Nm). Persisting acetylcholine causes repeated depolarisation of the muscle fibre, seen as spontaneous twitching. When the end plate stays depolarised, the nicotinic receptor desensitises and the muscle cannot respond to further nerve impulses - hence the later flaccid weakness.
One mechanism explains both the early twitching and the later paralysis: the same accumulated transmitter, first exciting then blocking, at a nicotinic synapse. The systemic picture is cholinergic crisis.
2. Atropine relieved the salivation, sweating and bradycardia, but the muscle weakness and fasciculations continued. Explain why, and state what else must be given and why timing matters.
Read the worked answer
Atropine is a competitive antagonist at muscarinic receptors, so M2 and M3 effects - secretions, sweating, heart rate, pupil - improve as the dose is titrated. It has no clinically useful blocking action at the nicotinic receptor of the motor end plate, so acetylcholine continues to accumulate at the neuromuscular junction; fasciculations persist and the weakness progresses to respiratory muscle failure.
The missing drug is an oxime such as pralidoxime. It reactivates the enzyme by removing the organophosphate group from the active-site serine. This works only while the phosphorylated enzyme can still be reactivated; with time the complex undergoes 'ageing' (dealkylation) and becomes permanently refractory. Because ageing can occur within hours for some compounds, the oxime must be given as early as possible - waiting until the patient is paralysed wastes the drug. If ageing has already occurred, recovery requires synthesis of new enzyme over weeks, so ventilatory support becomes the treatment.
The exam judgement: atropine treats the muscarinic half of the syndrome and saves the airway and heart; it does not treat the nicotinic half, which is what kills by apnea.
3. Is decontamination still necessary after atropine has been given? Why would succinylcholine be hazardous in this patient?
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Decontamination: yes, and urgently. Organophosphate persists on skin, hair and clothing and continues to be absorbed for hours; if absorption continues, acetylcholinesterase is re-inhibited as fast as it is reactivated, and atropine requirements escalate. Removing and bagging clothing, washing skin with soap and water, and protecting staff from contaminated runoff are part of treatment. Clinical improvement after atropine is not evidence that the depot is gone - it only shows that muscarinic receptors are blocked while the poison is still entering.
Succinylcholine: it is a depolarising neuromuscular blocker whose action is terminated rapidly by plasma butyrylcholinesterase. In organophosphate poisoning that enzyme is also inhibited, so succinylcholine is not broken down and can produce prolonged apnoea and paralysis. The safer choice, if neuromuscular blockade is needed for intubation, is a non-depolarising agent at a reduced dose with monitoring.
The linking principle is that organophosphates inhibit cholinesterases generally, not only the synaptic acetylcholinesterase - which is also why plasma cholinesterase is used as the diagnostic marker.