Depolarising Neuromuscular Blockers

Depolarising neuromuscular blockers activate the nicotinic acetylcholine receptor at the motor end plate, causing sustained depolarisation, fasciculation and then flaccid paralysis. Suxamethonium (succinylcholine) is the only member in clinical use. It has the fastest onset and shortest duration of any muscle relaxant, with specific and sometimes fatal risks.

Mechanism. Structurally two acetylcholine molecules joined together. It is not hydrolysed by acetylcholinesterase at the junction, so depolarisation persists until the drug diffuses away and is hydrolysed in plasma by butyrylcholinesterase (pseudocholinesterase).

Block types. Phase I block (depolarising): no fade, no post-tetanic potentiation, potentiated by anticholinesterases. Phase II block (after repeated doses over 3 to 5 mg/kg or infusion): resembles nondepolarising block with fade, may be partly reversed by anticholinesterases.

Pharmacokinetics. Onset 30 to 60 seconds intravenously, 2 to 3 minutes intramuscularly; duration 5 to 10 minutes; about 90% hydrolysed before reaching the junction.

Suxamethonium dosing.

• Adult intubation: 1 to 1.5 mg/kg intravenously (100 mg for 70 kg).
• Children: 1 to 2 mg/kg intravenously; infants up to 2 mg/kg.
• Intramuscular when no vein: 3 to 4 mg/kg adults (maximum 150 mg), 4 to 5 mg/kg in infants.
• Laryngospasm without access: 4 mg/kg intramuscularly or 0.1 to 0.5 mg/kg intravenously.
• Infusion (rare): 2 to 5 mg/min, with block monitoring.

Plasma cholinesterase deficiency. Atypical enzyme variants, liver disease, pregnancy, renal failure, organophosphate poisoning and certain drugs (neostigmine, ester local anaesthetics) can extend paralysis to 2 to 3 hours. Dibucaine number identifies variants.

Other relevant properties. Fasciculations, myalgia, raised intragastric, intraocular and intracranial pressure, masseter spasm, bradycardia (especially second doses and in children), hyperkalaemia, histamine release.

• First-line. Rapid sequence induction for emergency intubation.
• Alternative. Rocuronium 1.2 mg/kg when suxamethonium is contraindicated or when sugammadex is available for reversal.
• Specialist. Electroconvulsive therapy (0.5 to 1 mg/kg) and brief procedures needing short relaxation.
• Emergency. Laryngospasm; difficult airway where rapid recovery is desired (but not relied upon for rescue).

Selection. Use suxamethonium when speed matters and no contraindication exists; screen for hyperkalaemic risk, malignant hyperthermia and cholinesterase deficiency history; avoid in children unless airway emergency (risk of undiagnosed myopathy).

Contraindications.

• Known or suspected malignant hyperthermia susceptibility.
• Hyperkalaemia (potassium over 5.5 mmol/L) or risk of massive release: burns, crush injury, denervation, prolonged immobility, upper motor neurone lesion, severe sepsis, and muscular dystrophy or myopathy.
• Known plasma cholinesterase deficiency (relative).
• Acute narrow angle glaucoma or open eye injury (relative).

Serious adverse effects.

• Hyperkalaemic cardiac arrest (normal rise 0.5 mmol/L; much greater in at-risk patients).
• Malignant hyperthermia and masseter spasm.
• Bradycardia and asystole with repeated dosing, especially in children.
• Anaphylaxis.
• Prolonged paralysis from cholinesterase deficiency.
• Rhabdomyolysis in undiagnosed myopathy.

Major interactions. Anticholinesterases (neostigmine) and organophosphates prolong block; volatile anaesthetics, lithium, magnesium and aminoglycosides potentiate; chronic corticosteroid use may prolong; digoxin: arrhythmia with hyperkalaemia.

Prolonged block management. Maintain anaesthesia or sedation, ventilation and monitoring; confirm with TOF; give fresh frozen plasma or purified cholinesterase if available; test family for the variant afterwards.

Common prescribing errors.

• Giving suxamethonium in burns beyond 24 hours, prolonged ICU stay, or neuromuscular disease.
• Repeat doses without atropine in children.
• Failure to have sedation during prolonged paralysis.
• Using in suspected hyperkalaemia.
• Not recording the adverse event for family testing.

Special groups.

• Pregnancy: reduced cholinesterase prolongs effect but is rarely clinically significant.
• Breastfeeding: compatible.
• Children: avoid unless emergency; atropine 0.02 mg/kg available.
• Older adults: slower onset because of slower circulation.
• Kidney: safe if potassium is normal.
• Liver: prolonged effect in severe disease.
• East Africa: organophosphate exposure is common; suxamethonium block can last hours after exposure, so ask about pesticide exposure and prepare for prolonged ventilation.

Monitoring. ECG and potassium after any dose in at-risk patients; TOF count; end-tidal carbon dioxide; temperature; creatine kinase if myopathy or rhabdomyolysis is suspected.

Referral and escalation. Hyperkalaemic arrest (calcium chloride 10 mL of 10% intravenously, insulin and glucose, bicarbonate, salbutamol, and resuscitation); malignant hyperthermia (dantrolene); prolonged block (intensive care); genetic counselling.

Comparison with alternative classes. Suxamethonium gives the best intubating conditions fastest and ends quickly, but nondepolarising blockers with rapid reversal avoid hyperkalaemia, malignant hyperthermia and myalgia.