Neuromuscular Blocking Drugs

Neuromuscular blocking drugs interrupt transmission at the neuromuscular junction, producing skeletal muscle paralysis for tracheal intubation, surgical access and mechanical ventilation. They have no hypnotic or analgesic effect, so awareness is a risk unless anaesthesia is adequate. They are used only by clinicians able to secure the airway and ventilate.

Mechanism. Depolarising blockers (suxamethonium) act as acetylcholine agonists at the nicotinic receptor, causing persistent depolarisation. Nondepolarising blockers compete with acetylcholine without activating the receptor. Chemically they are aminosteroids (rocuronium, vecuronium, pancuronium) or benzylisoquinoliniums (atracurium, cisatracurium, mivacurium).

Pharmacokinetics. Onset depends on dose and potency (rocuronium 60 to 90 seconds at 1.2 mg/kg, suxamethonium 30 to 60 seconds). Duration is lengthened by volatile anaesthetics, hypothermia, acidosis, low potassium, magnesium and aminoglycosides.

Monitoring. Train-of-four (TOF) stimulation: the count shows depth; the ratio of fourth to first twitch shows recovery. Tracheal extubation requires a TOF ratio of 0.9 or more.

Differences. Atracurium releases histamine; cisatracurium does not. Pancuronium causes tachycardia through vagal blockade. Rocuronium is the usual alternative to suxamethonium. Atracurium and cisatracurium suit renal and hepatic failure.

• First-line. Rocuronium for intubation and rapid sequence induction; cisatracurium for long procedures and renal or hepatic failure; vecuronium where available.
• Alternative. Suxamethonium for rapid sequence induction when rocuronium cannot be reversed immediately or when very short action is needed; atracurium when cisatracurium is unavailable.
• Specialist. Infusion in intensive care for severe acute respiratory distress syndrome and raised intracranial pressure; mivacurium for short procedures.
• Emergency. Suxamethonium 1 to 1.5 mg/kg or rocuronium 1.2 mg/kg for emergency intubation; suxamethonium for laryngospasm unresponsive to oxygen and positive pressure.

Selection. Choose by speed needed, organ function, availability of reversal, histamine release risk, hyperkalaemia risk and cost. Always confirm anaesthesia depth before and during paralysis.

Contraindications. Inability to secure or ventilate the airway; known hypersensitivity; suxamethonium in hyperkalaemia, malignant hyperthermia susceptibility, myopathies and extensive burns, crush or denervation beyond 24 to 48 hours.

Serious adverse effects. Anaphylaxis (neuromuscular blockers are the most common cause of perioperative anaphylaxis), residual paralysis, hypoxia from apnoea, awareness during paralysis, histamine release and hypotension, tachycardia (pancuronium), critical illness myopathy with prolonged use and corticosteroids.

Major interactions. Volatile anaesthetics, aminoglycosides, magnesium, clindamycin, lithium, local anaesthetics and calcium channel blockers potentiate block; chronic phenytoin and carbamazepine reduce effect of nondepolarising blockers; neostigmine prolongs suxamethonium effect.

Common prescribing errors.

• Paralysis without adequate anaesthesia or airway plan.
• Dose by total instead of ideal body weight in obesity.
• Failure to monitor TOF.
• Giving a nondepolarising blocker after a recent suxamethonium dose without allowing recovery.
• Drawing up the wrong ampoule.

Special groups.

• Pregnancy: plasma cholinesterase is reduced, mildly prolonging suxamethonium; magnesium therapy potentiates blockers.
• Breastfeeding: compatible.
• Children: higher dose by weight for suxamethonium (1 to 2 mg/kg intravenously) and bradycardia risk; pretreat with atropine.
• Older adults: slower onset and longer duration.
• Kidney: avoid pancuronium; prolonged vecuronium and rocuronium; use cisatracurium.
• Liver: prolonged rocuronium and vecuronium; cisatracurium unaffected.
• East Africa: suxamethonium remains widely used where rocuronium or sugammadex are scarce; reversal agents and nerve stimulators may be unavailable, so plan extubation by clinical criteria.

Monitoring. TOF count and ratio at the adductor pollicis; clinical signs (sustained head lift for 5 seconds, tidal volume); depth of anaesthesia; ventilatory support until recovery.

Referral and escalation. Anaphylaxis, prolonged paralysis beyond expected time, suspected malignant hyperthermia, residual block after reversal.

Comparison with alternative classes. Neuromuscular blockers give optimal surgical and intubating conditions, but deep anaesthesia and high-dose opioid alone can sometimes provide intubating conditions without paralysis at the cost of haemodynamic compromise.