1. 4th year Anaesthesia MBChB
Muscle Relaxants
4th year Anaesthesia
MBChB

2. Triad of Anaesthesia
Hypnosis
Analgesia
Muscle Relaxation

3. Physiology of the NMJ (neuromuscular junction)
Excitation-contraction coupling
Nervous impulse is converted into a skeletal muscle contraction at the NMJ
Acetylcholine (Ach)
Key neurotransmitter at the NMJ
Formed from ACETYL CoA + CHOLINE
Stored in pre-synaptic vesicles
Binds to NICOTINIC cholinergic receptors on post-junctional membrane
Broken down by Acetylcholinesterase (AChE)

4. Terminal axon of motor nerve
Physiology
Terminal axon of motor nerve

5. Ach Release blocked by:
Physiology
Ach Release blocked by:
Magnesium
Aminoglycosides
Botox!

6. Pharmacology 3 ways to achieve muscle relaxation Blocking the ...
nerve (local anaesthetics)
NMJ (muscle relaxants)
muscle (dantrolene)

7. History Dates back to the 16th century
European explorers encountered the Amazonians in South America using poison arrows that produced death by skeletal muscle paralysis!
This poison, known today as curare
active ingredient, tubocurarine

8. History
By 1943, neuromuscular blocking drugs became established as muscle relaxants in the practice of anaesthesia and surgery

9. Neuromuscular Blockers
2 types
Depolarisers
Non-depolarisers

10. Mechanism of Action Non-depolarisers Depolarisers Competitive
Compete with Ach for nicotinic receptors
Require reversal
Depolarisers
Non-competitive
Cannot be reversed

11. ED95 Dose of muscle relaxant that will paralyse 95% of normal people
Usual intubating does: 2 x ED95

12. Total paralysis Adequate does of muscle relaxant will result in:
Inability to breath
Inability to maintain an airway
Loss of protective reflexes
Consciousness is completely unimpaired!!!

14. Potentiating factors of muscle relaxants Drugs Inhalational agents
Aminoglycoside antibiotics
Electrolytes
↓ Calcium
↑ Magnesium
↑ Potassium
Acidosis
Temperature
Cold – sux
Warm – non-depolarisers
(potential problem post-op ‘recurarisation’)
Diseases
Myaesthenia gravis
Muscular dystrophies, dystonias, myopathies

15. Indications Improved surgical access
Facilitate intubation or bronchoscopy
Prevention of movement in microsurgery
Unconscious patients can still move!
Manipulation of fractures
Prevention of / treatment of convulsions
ICU
Tetanus
Severe lung disease
Severe uncontrolled shivering
Severe ↑ ICP

16. So, the person administering the
Precautions
So, the person administering the
muscle relaxant must...
1) assess the airway
2) be competent in maintenance of a patent airway
3) have necessary equipment
Must ventilate a patient who you paralyse
IPPV with the mechanical ventilator
Reservoir bag
Self-inflating bag (ambubag)
Via...
Facemask
LMA
ETT

17. Specific Muscle Relaxants

18. Suxamethonium Excretion: Chemical structure: Amp: 100mg (2mls)
2 Ach molecules
Amp: 100mg (2mls)
Dose: 1-2mg / kg
Effects:
Profound paralysis in 60sec
Ultra-shortacting
fasciculations
Lasts 5 minutes
Excretion:
Metabolised by pseudocholinesterase or plasma cholinesterase
Synthesised in liver
Found in plasma
Markedly ↓ed in SCOLINE APNOEA
Inherited homozygous or heterozygous
Prolonged paralysis
Supportive treatment with ventilation + sedation
FFPs

19. Suxamethonium Side-effects: Contra-indications: Scoline pains
Bradycardias
Hyperkalaemia and arrhythmias, even cardiac arrest
Triggers Malignant Hyperthermia
Scoline Apnoea
Histamine release
Anaphylaxis
Contra-indications:
Drug allergy
Scoline apnoea MH
Unknown myopathies
Risk of hyperkalaemia
Renal failure
Paralysis
Crush / Burn injury

20. Non-depolarisers Types: Doses: based on lean body mass
Benzolisoquinolinium compounds
Curare, alcuronium, atracurium, cisatracurium, mivacurium
Aminosteroids
Rocuronium, vecuronium, pancuronium
Doses: based on lean body mass
Physical properties:
2 – 5ml ampoules
May require refrigeration

21. Non-depolarisers Clinical effects: Metabolism: Excretion:
Marked paralysis in 1 – 5 minutes
No fasciculations
Duration is variable
Short-acting
Intermediate-acting
Long-acting
Metabolism:
Hepatic
Hoffman degradation
Excretion:
Renal
Hepatobiliary
Pseudocholinesterase

22. Reversal of neuromuscular blockade
Neostigmine
Acetylcholinesterase inhibitor
Increase Ach concentration in synaptic cleft
Ach COMPETES with NDMR
Others: pyridostigmine, edrophonium, organophosphates
But Ach ↑es at nicotinic and muscarinic receptors
Anticholinergic
ANTI-MUSCARINIC
Atropine or glycopyrrolate
Bad muscarinic effects (the B’s)
Bronchial secretions
Bronchospasm
Bradycardia
Beristalsis (peristalsis)
Dose:
Neostigmine 2.5mg
Glycopyrrolate mg

23. Assess readiness for reversal
Peripheral nerve stimulator
Train-of-four
With 4 twitches: 75% of NMJs still blocked
Beware the patient with compromised liver or kidney function

24. Inadequate Reversal “fish out of water” Jerky respiration Reduced VT
Tracheal tug
Restlessness, may be worsened by hypoxia
Inability to raise head from pillow
Weak hand grip
Poor ability to cough
ptosis
“fish out of water”

25. This is how our patients feel when they are partially
reversed

26. Management of Inadequate Reversal
Exclude another cause
Anaesthetic agents, analgesia, hypo or hypercarbia, CVA
Maintain ventilation
Reverse any potentiators
Warm patient
Check Mg, K, Ca
Use PNS
Repeat dose neostigmine (max: 5mg)
Neostigmine in bigger doses can may cause weakness

27. Pancuronium Kept in fridge Vagolytic – tachycardia
No histamine release
Long-acting

28. Vecuronium Kept in fridge Cardiovascularly stable No histamine release
Intermediate-acting
Largely hepato-biliary excretion therefore safe in renal failure

29. Rocuronium Kept in fridge Cardiovascularly stable
High dose: 1mg/kg can provide intubating conditions within 1 minute
Modified RSI
Intermediate duration of action

30. Atracurium Fridge Histamine releasing Hoffman degradation
Increased risk of anaphylaxis
Hoffman degradation
Spontaneous
Dependent on pH and temperature
Side-effect: laudanosine
Safe in renal failure
Intermediate duration of action

31. Cisatracurium Fridge No histamine release
Safe in renal failure (Hoffmann Degradation)
Intermediate-acting