Non-Depolarising Neuromuscular Blockers

Non-depolarising NMBs are muscle relaxants used to:

  • Facilitate laryngoscopy and tracheal intubation
  • Control ICP
  • Improve respiratory system compliance
  • Improve patient safety on transportation

Mechanism of action is by competitive antagonism of ACh at the NMJ, preventing generation of end-plate potentials. Effective pharmacodynamic response requires >70% receptor occupation.

Common Features of Neuromuscular Blockers

Property Action
Route of Administration IV/IM
Distribution Small VD as they are polar and unable to cross lipid membranes
Elimination Reduced urinary clearance which prolongs the mechanism of action of aminosteroids in renal failure
Resp Apnoea
MSK ↑ Duration in hypothermia
Renal ↑ Duration in acidosis, ↑ duration in hypokalaemia, ↓ duration in hyperkalaemia, ↑ duration in hypermagnesaemia
Metabolic Critical Illness Myopathy in patients with long-term relaxant use

The ED95 is:

  • The dose of a neuromuscular blocking drug required to produce a 95% reduction in twitch height in 50% of the population
  • A commonly-used therapeutic end-point for neuromuscular blocking drugs
    Typically, induction doses used are 2-5x the ED95.

Comparison of Neuromuscular Blockers

Property Rocuronium Vecuronium Pancuronium Atracurium Cisatracurium
Class Aminosteroid Aminosteroid Bis-quaternary aminosteroid Benzylisoquinolinium derivative Benzylisoquinolinium derivative
Presentation Clear, colourless solution at 10 mg.ml-1 10mg powder for reconstitution in water. Contains mannitol and NaOH. Colourless solution at 2 mg.ml-1, which must be stored at 4°C Colourless solution at 10mg.ml1, which should be stored at 4°C. Mixture of all ten extant diastereoisomers. R-Cis, R'-Cis isomer of atracurium, which is 15% of atracurium by weight but provides 50% of its NMBD action.

Colourless solution at 2-5mg.ml-1, which should be stored at 4°C
Intubating Dose 0.6-1.2 mg.kg-1 0.1 mg.kg-1 0.05-0.1 mg.kg-1 0.5 mg.kg-1 0.15-0.2mg.kg-1
ED95 0.3 mg.kg-1 0.05 mg.kg-1 0.07 mg.kg-1 0.25 mg.kg-1 0.05 mg.kg-1
Onset 45-90s 90-120s 90-150s 90-120s 60-180s
Duration ~30 minutes with normal renal function, repeat doses may be more unpredictable 45-65 minutes 60-100 minutes 15-35 minutes 25-30 minutes
Metabolism < 5% hepatic deacetylation to inactive metabolites 20% heptic de-acetylation with weakly active metabolites 20% heptic de-acetylation with weakly active metabolites 60% by ester hydrolysis, with remainder by Hofmann elimination.

Metabolised to laudanosine, which causes seizures in high concentrations (relevant when administered by long infusion)
Hofmann elimination
Elimination 60% biliary, 40% urinary. Prolonged duration in hepatic and renal failure 70% biliary, 30% urinary 80% biliary, 20% urinary
Resp Slight risk of bronchospasm with rapid injection Slight risk of bronchospasm with rapid injection
CVS HR at high doses NoHR HR and MAP due to muscarinic antagonism Risk of ↓ BP with rapid injection Risk of ↓ BP with rapid injection
Immune Higher risk of anaphylaxis, ~6/100,000. Anaphylaxis risk associated with use of pholcodeine in the previous 3 years. Notably no anaphylaxis recorded in NAP 6 Anaphylaxis ~ 4/100,000.
Other Reversible with sugammadex Reversible with sugammadex

References

  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
  3. Crilly H, Rose M. Anaphylaxis and anaesthesia – can treating a cough kill?. Aust Prescr. 2014;37:74-6.
  4. Lexicomp. Rocuronium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
  5. Lexicomp. Vecuronium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
  6. Lexicomp. Pancuronium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
  7. Lexicomp. Atracurium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
  8. Lexicomp. Cisatracurium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
  9. Cook T, Harper N. Anaesthesia, Surgery, and Life-Threatening Allergic Reactions: Report and findings of the Royal College of Anaesthetists' 6th National Audit Project: Perioperative Anaphylaxis. Royal College of Anaesthetists'. 2018.
Last updated 2018-05-31

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