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Myasthenia, LEMS & cholinergic crisis

Three conditions at the same synapse. One is postsynaptic, one is presynaptic, and one is too much of the treatment — and each behaves completely differently under anaesthesia.

Where each lesion sits

Fix the anatomy first and almost everything else follows: where the problem is predicts the antibody, the exercise response, and the relaxant sensitivity.

Presynaptic

LEMS — Ca²⁺ channel

Postsynaptic

MG — ACh receptor

The cleft

cholinergic — excess ACh

Myasthenia gravis vs LEMS

If you remember only one line: myasthenia gets worse with use, LEMS gets better. Nearly every other difference is downstream of the presynaptic versus postsynaptic lesion.

	Myasthenia gravis	Lambert–Eaton (LEMS)
Lesion site	Postsynaptic — muscle membrane	Presynaptic — nerve terminal
Antibody	Nicotinic ACh receptor (85%); MuSK in ~5%	P/Q-type voltage-gated Ca²⁺ channel
Mechanism	Receptor blockade, complement damage, increased turnover → fewer functioning receptors	Reduced Ca²⁺ entry → fewer ACh vesicles released per impulse
Effect of exercise	Worse — fatigability is the hallmark	Better — post-tetanic facilitation as Ca²⁺ accumulates
Distribution	Ocular first (ptosis, diplopia) in 50–60%; then bulbar, then limb	Proximal limbs first, legs before arms; ocular and bulbar mild or absent
Reflexes	Preserved	Reduced or absent; may return after sustained contraction
Autonomic features	Absent	Common — dry mouth, constipation, impotence
Association	Thymoma 10–15%, thymic hyperplasia; other autoimmune disease	Small cell lung cancer in 50–60% — often precedes the diagnosis
Repetitive nerve stimulation	Decrement at low frequency (2–3 Hz)	Increment at high frequency (20–50 Hz) or after exercise
Anticholinesterase response	Good — pyridostigmine works	Poor — 3,4-diaminopyridine is used instead
Suxamethonium	Resistant — needs a larger dose	Sensitive
Non-depolarising relaxant	Very sensitive — reduce to 10–20% or avoid	Very sensitive — even more profound and prolonged
Treatment	Pyridostigmine, steroids, azathioprine, thymectomy; IVIG or plasma exchange in crisis	Treat the underlying tumour; 3,4-diaminopyridine, IVIG, immunosuppression

The relaxant table is the examinable core

Myasthenia is the counter-intuitive one: RESISTANT to suxamethonium but EXQUISITELY SENSITIVE to non-depolarisers. Fewer receptors means more suxamethonium is needed to depolarise enough of them, while the reduced safety margin means a tiny dose of rocuronium produces profound block.
LEMS is sensitive to everything. Both classes, profoundly and unpredictably.
In both, use quantitative neuromuscular monitoring, avoid relaxants where you can (TIVA with remifentanil, or regional), and titrate to twitch response rather than to weight.
Sugammadex is useful in myasthenia, but it does not remove the need for monitoring — residual weakness is disease, not just drug.

Myasthenic vs cholinergic crisis

Both present as a weak myasthenic patient in respiratory failure. The difference is too little versus too much acetylcholine — and the muscarinic signs give it away.

	Myasthenic crisis	Cholinergic crisis
Cause	Undertreatment, or a trigger: infection, surgery, pregnancy, tapering steroids, or a precipitating drug	Overtreatment with anticholinesterase; or organophosphate poisoning
Mechanism	Too few functioning receptors	ACh excess → persistent depolarising block
Pupils	Normal or dilated	Miosis
Secretions	Normal	Profuse — salivation, lacrimation, bronchorrhoea
Fasciculations	Absent	Present
Heart rate	Tachycardia	Bradycardia
Gut	Normal	Cramps, diarrhoea, vomiting
Edrophonium test	Improves	Worsens
Management	Support ventilation; IVIG or plasma exchange; increase immunosuppression; treat the trigger	Stop the anticholinesterase; atropine for muscarinic effects; pralidoxime if organophosphate; ventilate

Cholinergic excess — the two receptor families

Muscarinic (SLUDGE / DUMBBELS): Salivation, Lacrimation, Urination, Defecation, GI cramps, Emesis — plus bradycardia, bronchorrhoea, bronchospasm and miosis. These are the ones atropine reverses.
Nicotinic: fasciculations, cramps, then weakness and paralysis. Atropine does not touch these — that is why ventilation is the priority and pralidoxime is needed to reactivate the enzyme in organophosphate poisoning.
CNS: anxiety, confusion, seizures, coma.
The classic killer is bronchorrhoea with bronchospasm — patients drown in secretions. Give atropine in escalating doses titrated to drying of secretions, not to heart rate.

The edrophonium (Tensilon) test

Edrophonium is a very short-acting anticholinesterase (onset 30 s, duration about 5–10 min). It improves myasthenic crisis and worsens cholinergic crisis.
It is now rarely performed — the risk of precipitating severe bradycardia or worsening a cholinergic crisis outweighs the benefit, and antibody testing plus electrophysiology have largely replaced it.
If it is done: have atropine drawn up, full monitoring and resuscitation facilities available.

Anaesthetic management of myasthenia

Preoperative

Assess bulbar and respiratory function — vital capacity, ability to swallow and cough, and existing ventilatory support.
Optimise treatment and consider IVIG or plasma exchange before major surgery. Decide with the neurologist whether to continue pyridostigmine on the day.
Osserman criteria predict the need for postoperative ventilation: disease duration over 6 years, coexisting respiratory disease, pyridostigmine over 750 mg/day, and vital capacity under 2.9 L.

Intraoperative and postoperative

Regional or local anaesthesia where possible. Amide local anaesthetics are preferred; esters rely on plasma cholinesterase, which anticholinesterases inhibit.
If general anaesthesia is needed, favour TIVA with remifentanil and no relaxant, or volatile alone — volatiles themselves provide useful relaxation and potentiate any blocker given.
If a relaxant is unavoidable, use a small dose of a short-acting non-depolariser with quantitative train-of-four monitoring, and reverse with sugammadex where an aminosteroid was used.
Plan for possible postoperative ventilation and a higher level of care. Avoid drugs that worsen weakness: aminoglycosides, magnesium, beta blockers, quinolones, phenytoin.