Download Neuromuscular Blockade - Health Education East Midlands VLE

Neuromuscular Blockade
Suzanne Wake
NEMSA SpR
September 2008
Objective
Safe use of Neuromuscular Blockade
Contents
• Physiology of neuromuscular junction
(NMJ)
• Pharmacology of commonly used
neuromuscular blocking drugs (NMBDs)
• Monitoring neuromuscular blockade
(MNB)
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)
Structure of NMJ
Physiology - Acetylcholine
• Synthesised in presynaptic neurone
• Nerve stimulus
release into synaptic
cleft
• Binds to post-synaptic
Ach-r
• Hydrolysed by
Acetylcholinesterase
(Ach-E)
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
Pharmacology - Structure of
NMBDs
• Quaternary ammonium compounds related to
Ach
Pharmacology–Classification of
NMBDs
• Depolarising NMBDs
• Non-depolarising NMBDs
Depolarising NMBDs
• Ach-r agonists
• Succinylcholine
Succinylcholine
• Binds to Ach-r causing
– 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
Side Effects of Succinylcholine
LETHAL
NON-LETHAL
Anaphylaxis
Bradycardia
intraocular
intracranial
intragastric pressure
Myalgia
Prolonged action (pCh
deficiency)
Myotonia
contracture
Arrest
(muscarinic effect)
Hyperkalaemia
MH trigger
Non-Depolarising NMBDs
• Competitive, reversible antagonists at
postsynaptic Ach-r
• 75% Ach-r block for loss of contraction
• Benzolisoquinoliniums (--curium)
• Aminosteroids (--curonium)
Benzolisoquinolonium Compounds
• Histamine release
• Atracurium
– Hofmann degradation (45%)
– Ester hydrolysis
• Mivacurium
– Short acting
– Hydrolysed by plasma cholinesterases
Aminosteroid Compounds
• No histamine release
• Depend on organ function for excretion
• Rocuronium
– Rapid onset
– Hepatic excretion
– Anaphylactoid rxns more common
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
Monitoring NMB – Why?
•
•
•
•
Timing of tracheal intubation
Intra-operative muscle relaxation
Reversal of NMB
Timing of tracheal extubation
Monitoring NMB – How?
•
•
•
•
Supra-maximal stimulus (15-60mA)
Elicit whole muscle response
Square wave stimulus
Duration < refractory period of NMJ
Patterns of Stimulation
•
•
•
•
Single Twitch
Train of Four (TOF)
Tetany
Double Burst Stimulation
Single Twitch
• 0.1-1Hz
• Requires control measurement (T1/Tc)
• Depolarising block
100%
Tc
T1
T2
T3
T4
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
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
Double Burst Stimulation
• 3, 50Hz twitches, 750ms pause, repeat
• Improves manual detection of fade
– Perceived at TOF ratio 0.6 cf 0.4
Summary
Reversal of NMB
• Neostigmine
PLUS
• Antimuscarinic
OR
• Sugamadex (the future)