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% hepatic deacetylation with weakly active metabolites | 20% hepatic deacetylation 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 | No ↑ HR | ↑ 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 pholcodine in the previous 3 years. | Notably no anaphylaxis recorded in NAP 6 | Anaphylaxis ~ 4/100,000. | ||
| Other | Reversible with sugammadex | Reversible with sugammadex |
References
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
- Crilly H, Rose M. Anaphylaxis and anaesthesia – can treating a cough kill?. Aust Prescr. 2014;37:74-6.
- Lexicomp. Rocuronium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
- Lexicomp. Vecuronium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
- Lexicomp. Pancuronium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
- Lexicomp. Atracurium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
- Lexicomp. Cisatracurium: Drug information. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2017.
- 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.