1. Neuromuscular Blockade
Suzanne Wake
NEMSA SpR
September 2008

2. Objective
Safe use of Neuromuscular Blockade

3. Contents Physiology of neuromuscular junction (NMJ)
Pharmacology of commonly used neuromuscular blocking drugs (NMBDs)
Monitoring neuromuscular blockade (MNB)

4. Physiology - Structure of NMJ
NMJ consists of
Pre-synaptic motor neurone
Synaptic cleft (20nm)
Motor end plate
ie post-synaptic membrane of striated muscle cell, rich in acetylcholine receptors (Ach-r)
NMJ consists of Motor

5. Structure of NMJ

6. Physiology - Acetylcholine
Synthesised in pre-synaptic neurone
Nerve stimulus release into synaptic cleft
Binds to post-synaptic Ach-r
Hydrolysed by Acetylcholinesterase (Ach-E)

7. Physiology – Acetylcholine Receptor
Nicotinic
Pentameric cylinder
2 a sub-units = 2 Ach binding sites
Transmembrane
Central ion channel
Ach binding conformation change channel opens a a

8. Pharmacology - Structure of NMBDs
Quaternary ammonium compounds related to Ach

9. Pharmacology–Classification of NMBDs
Depolarising NMBDs
Non-depolarising NMBDs

10. Depolarising NMBDs
Ach-r agonists
Succinylcholine

11. Succinylcholine Binds to Ach-r causing Phase 1 (Accomodation) Block
Membrane depolarisation
Prolonged activation of Ach-r
Muscle flaccidity (<60s)
Phase 1 (Accomodation) Block
Recovery as drug diffuses away (3-15 mins)
Metabolised by plasma cholinesterase

12. Side Effects of Succinylcholine
LETHAL
Anaphylaxis
Bradycardia Arrest
(muscarinic effect)
Hyperkalaemia
MH trigger
NON-LETHAL
intraocular
intracranial
intragastric pressure
Myalgia
Prolonged action (pCh deficiency)
Myotonia contracture

13. Non-Depolarising NMBDs
Competitive, reversible antagonists at postsynaptic Ach-r
75% Ach-r block for loss of contraction
Benzolisoquinoliniums (--curium)
Aminosteroids (--curonium)

14. Benzolisoquinolonium Compounds
Histamine release
Atracurium
Hofmann degradation (45%)
Ester hydrolysis
Mivacurium
Short acting
Hydrolysed by plasma cholinesterases

15. Aminosteroid Compounds
No histamine release
Depend on organ function for excretion
Rocuronium
Rapid onset
Hepatic excretion
Anaphylactoid rxns more common

16. Ideal NMBD Nondepolarising Rapid onset/offset Reversible with AchE
No histamine release
No CVS effects
Non-cumulative
No drug interactions
No organ toxicity or excretion

17. Monitoring NMB – Why? Timing of tracheal intubation
Intra-operative muscle relaxation
Reversal of NMB
Timing of tracheal extubation

18. Monitoring NMB – How? Supra-maximal stimulus (15-60mA)
Elicit whole muscle response
Square wave stimulus
Duration < refractory period of NMJ

19. Patterns of Stimulation
Single Twitch
Train of Four (TOF)
Tetany
Double Burst Stimulation

20. Single Twitch 0.1-1Hz Requires control measurement (T1/Tc)
Depolarising block
100% Tc T1 T2 T3 T4

21. Train of Four 2Hz Nondepolarising block TOF ratio (T4/T1)
Fade (presynaptic Ach-r block)
T4/T1>0.9 for safe extubation
100% T1 T2 T3 T4

22. Tetany 50-100Hz for 5s Nondepolarising and phase 2 block show fade
Post Tetanic Facilitation
50Hz for 5s, 3s pause, 1Hz single stimuli
Used in profound nondepolarising NMB

23. Double Burst Stimulation
3, 50Hz twitches, 750ms pause, repeat
Improves manual detection of fade
Perceived at TOF ratio 0.6 cf 0.4

24. Summary

25. Reversal of NMB Neostigmine PLUS Antimuscarinic OR
Sugamadex (the future)