Key Facts

NMBAs are essential drugs in anaesthetic practice, enabling tracheal intubation, surgical relaxation, and ventilator synchrony. Understanding their pharmacology and the importance of neuromuscular monitoring is critical for patient safety.

Epidemiology

NMBAs are used in approximately 50-60% of all general anaesthetics. Residual neuromuscular blockade (TOF <0.9) in PACU is common (~30-40%) and is associated with a 3-fold increase in respiratory complications. Sugammadex has significantly reduced the incidence of residual paralysis.

Aetiology

Classification:

• Depolarising: Suxamethonium — mimics ACh, causing initial depolarisation (fasciculations) followed by block
• Non-depolarising: Competitive antagonists at nicotinic ACh receptors; aminosteroids (rocuronium, vecuronium, pancuronium) and benzylisoquinoliniums (atracurium, cisatracurium, mivacurium)

Pathophysiology

Normal neuromuscular transmission: ACh released from motor nerve terminal → binds nicotinic receptors on motor end-plate → sodium influx → depolarisation → muscle contraction → ACh hydrolysed by acetylcholinesterase

Depolarising block (Phase I): Suxamethonium binds receptor, causes sustained depolarisation → initial fasciculation then flaccid paralysis. Not reversed by anticholinesterases.

Non-depolarising block: Competitive antagonism at nicotinic receptor → prevents ACh binding → no depolarisation → flaccid paralysis. Reversed by anticholinesterases (neostigmine) or sugammadex (rocuronium/vecuronium).

Suxamethonium Effects

• Fasciculations followed by complete paralysis
• Jaw relaxation within 45-60 seconds
• Duration 5-10 minutes (plasma cholinesterase metabolism)
• Side effects: K⁺ rise (0.5-1 mmol/L), raised IOP, raised ICP, bradycardia (especially repeat doses), masseter spasm, malignant hyperthermia trigger

Non-Depolarising Block

• Gradual onset of paralysis (60-120s for rocuronium, 2-3 min for atracurium)
• Duration 20-50 minutes depending on agent
• No fasciculations
• Histamine release with atracurium (flushing, bronchospasm, hypotension — less with cisatracurium)

Residual Neuromuscular Block

• Subjective weakness, inability to sustain head lift for 5 seconds
• Reduced tidal volume, hypoxia, inability to clear secretions
• Objective: TOF ratio <0.9

Red Flags

• Prolonged block after suxamethonium (>20 min) — plasma cholinesterase deficiency
• TOF ratio <0.9 at extubation — risk of respiratory failure in PACU
• Masseter spasm after suxamethonium — may be early sign of malignant hyperthermia
• Unexplained tachycardia with rising ETCO2 after suxamethonium — suspect MH

Bedside

• Peripheral nerve stimulator (TOF monitor): Mandatory when NMBAs used
• TOF count: Number of twitches visible (0-4); count ≥2 required before neostigmine reversal
• TOF ratio: Quantitative — ratio of 4th to 1st twitch; >0.9 required for safe extubation
• Post-tetanic count (PTC): Assess deep block when TOF count = 0

Bloods

• Plasma cholinesterase levels: If suxamethonium apnoea suspected
• Dibucaine number: Normal 80%; heterozygous atypical 40-70%; homozygous atypical <20%
• Serum tryptase: If anaphylaxis to NMBA suspected

Imaging

• Not applicable

Special Tests

• Quantitative neuromuscular monitoring (acceleromyography): Gold standard — TOFscan, TOF-Watch
• Allergy testing: Skin prick and intradermal for NMBA allergy (most common drug cause of perioperative anaphylaxis)

Non-pharmacological

• Neuromuscular monitoring: Use TOF monitor for ALL patients receiving NMBAs
• Clinical assessment: Head lift for 5s, grip strength, tongue protrusion — but objective monitoring preferred
• Ventilatory support: Continue ventilation until adequate reversal confirmed

Pharmacological

• Neostigmine 2.5mg + glycopyrrolate 0.5mg IV: Standard reversal of non-depolarising block; only effective at TOF count ≥2; glycopyrrolate prevents neostigmine-induced bradycardia
• Sugammadex: Dose depends on depth of rocuronium/vecuronium block:
  • TOF count ≥2: 2mg/kg
  • PTC ≥1 (deep block): 4mg/kg
  • Immediate reversal (CICO/failed intubation): 16mg/kg
• Suxamethonium apnoea management: Ventilate, sedate, monitor TOF, await spontaneous recovery; do NOT give neostigmine

Surgical/Interventional

• Not applicable

Referral Criteria

• Suxamethonium apnoea — anaesthetic follow-up, plasma cholinesterase testing, family screening, issue of alert card
• Suspected NMBA anaphylaxis — allergy clinic referral (6 weeks post-event)
• Myasthenia gravis — joint anaesthetic-neurological planning

• Sugammadex reversal: Complete reversal within 2-3 minutes (even from deep block)
• Residual paralysis: Incidence reduced from 30-40% to <5% with routine sugammadex use and quantitative monitoring
• Suxamethonium apnoea: Homozygous atypical cholinesterase (~1:25,000) — paralysis may last 4-8 hours; excellent prognosis with supportive care
• NMBA anaphylaxis: Rocuronium and suxamethonium are the most common causes of perioperative anaphylaxis (NAP6); mortality <5% with prompt treatment

Comparison of Common NMBAs

Sugammadex Dosing Guide