Nondepolarising Neuromuscular Blockers

Nondepolarising neuromuscular blockers are competitive antagonists of acetylcholine at the postsynaptic nicotinic receptor. They produce flaccid paralysis without fasciculation, and the block is reversible by increasing acetylcholine with anticholinesterases or by encapsulating aminosteroids with sugammadex. They are the usual relaxants for maintenance of paralysis during anaesthesia and intensive care.

Mechanism. Binding of two receptor subunits prevents opening of the ion channel. Fade on repetitive stimulation, post-tetanic potentiation and sensitivity to volatile agents are characteristic. Presynaptic effects explain fade.

Classes.

• Aminosteroids: rocuronium, vecuronium, pancuronium.
• Benzylisoquinoliniums: atracurium, cisatracurium, mivacurium.

Pharmacokinetics. Distribution is rapid; recovery from a single dose is by redistribution, then elimination. Elimination depends on drug: biliary (rocuronium, vecuronium), renal (pancuronium), Hofmann and ester hydrolysis (atracurium, cisatracurium), plasma cholinesterase (mivacurium).

Rocuronium. Fastest onset; prolonged in older adults, hepatic and renal disease; anaphylaxis occurs. Dose by ideal body weight in obesity.

Vecuronium. Cardiovascularly stable; active metabolite accumulates in renal failure and prolonged infusion.

Atracurium and cisatracurium. Organ-independent elimination. Atracurium releases histamine (flushing, hypotension) at doses over 0.5 mg/kg; cisatracurium does not. Laudanosine from both can accumulate and lower seizure threshold.

Pancuronium. Vagolytic and sympathomimetic, tachycardia and hypertension; long duration; renal elimination.

• First-line. Rocuronium for tracheal intubation and rapid sequence induction; cisatracurium for maintenance in organ failure and for infusions.
• Alternative. Vecuronium or atracurium for routine surgery.
• Specialist. Infusion for acute respiratory distress syndrome, therapeutic hypothermia, status asthmaticus and raised intracranial pressure; mivacurium for short procedures.
• Emergency. Rocuronium 1.2 mg/kg for rapid sequence intubation with sugammadex available.

Selection. Choose by speed, organ function, histamine and cardiovascular profile, and reversal options. Use ideal body weight dosing in obesity. Use quantitative neuromuscular monitoring for every dose.

Contraindications. Hypersensitivity; absence of airway control and ventilation; pancuronium in tachyarrhythmia and renal failure; atracurium in severe asthma (relative).

Serious adverse effects. Anaphylaxis (aminosteroids, especially rocuronium; cross-reactivity between neuromuscular blockers is common), residual neuromuscular block, histamine release, awareness, critical illness myopathy and prolonged weakness with infusions and corticosteroids, tachycardia (pancuronium).

Major interactions. Potentiated by volatile agents, aminoglycosides, polymyxins, clindamycin, magnesium sulphate, lithium, calcium channel blockers, local anaesthetics, dantrolene and hypothermia; reduced by chronic phenytoin or carbamazepine, hypercalcaemia and burns; earlier suxamethonium may potentiate a later nondepolarising dose.

Common prescribing errors.

• Dosing by actual weight in obesity.
• Giving a repeat dose without TOF count.
• Using usual doses in myasthenia gravis (extreme sensitivity).
• Mixing neuromuscular blocker syringes with induction drugs.
• Omitting sedation in paralysed patients.

Special groups.

• Pregnancy: magnesium potentiates; reduce doses in pre-eclampsia on magnesium.
• Breastfeeding: compatible.
• Children: weight-based dosing; neonates have increased sensitivity.
• Older adults: slower onset and longer duration.
• Kidney: prefer cisatracurium or atracurium; avoid pancuronium.
• Liver: prefer cisatracurium; allow longer action of rocuronium and vecuronium.
• Burns: resistance to nondepolarising blockers after 48 hours.
• East Africa: nerve stimulators and reversal agents may be unavailable; limit doses, extend extubation criteria and have ventilation capacity.

Monitoring. Train-of-four count and ratio, acceleromyography when available, end-tidal carbon dioxide, anaesthetic depth, temperature, electrolytes (potassium, calcium, magnesium).

Referral and escalation. Anaphylaxis (adrenaline, fluids, airway); prolonged weakness; failure to reverse; intensive care review for infusion-related myopathy.

Comparison with alternative classes. Nondepolarising agents avoid hyperkalaemia, malignant hyperthermia and fasciculation, and can be reversed, but have slower onset (except high-dose rocuronium) and carry residual block risk.