Overview Of Neuromuscular Blockade & Specific NMDRs

Question 1

The Neuromuscular Junction (NMJ) in Skeletal Muscle

Answer 1

Excitation-contraction coupling: Nervous impulse is converted into a skeletal muscle contraction at the NMJ

Question 2

Acetylcholine (Ach)

Answer 2

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)

Question 3

Ach release blockers (BAM)

Answer 3

Botox
Aminoglycoside
Magnesium
(tubocurarine= block NMJ from binding to ACH receptor)

Question 4

How is Muscle Relaxation Achieved

Answer 4

Blocking Motor Nerves= local anaesthetics
Blocking The NMJ= IV muscle relaxants (neuromuscular blockers
Blocking receptors inside cells= Dantrolene

Question 5

Classification of Neuromuscular Blockers

Answer 5

A) Depolarising=> Suxamethonium

B) Non-depolarising=> all other muscle relaxants

Question 6

Depolarising agent

Answer 6

Non-competitive action

Cannot be reversed… wear off / are metabolised over time

Question 7

Non-depolarisers

Answer 7

Competitive inhibition
Compete with Ach for nicotinic receptors
Require reversal

Question 8

ED95

Answer 8

“Effective Dose”
Dose of muscle relaxant that will paralyse 95% of normal people
Usual intubating does: 2 x ED95

Question 9

Adequate paralysis

Answer 9

Adequate dose of muscle relaxant will result in:
Inability to breathe
Inability to maintain an airway
Loss of protective reflexes
Consciousness is completely unimpaired!!!

Question 10

Factors that potentiate muscle relaxants

Answer 10

Drugs= inhalation agents and aminoglycosides antibiotics
Electrolytes: low Calcium, high magnesium and low potassium.
pH: Acidosis
Temperature: cold; warm (non-depolarisers)
Diseases: myasthenia gravis; muscular dystrophy, dytonia and myopathies and renal failure

Question 11

Some clinical examples where muscle relaxants are used

Answer 11

Improved surgical access (abdominal surgery)
Facilitate intubation or bronchoscopy
Prevention of movement in microsurgery
Manipulation of fractures
Preventing / mitigating physical effects of convulsions
ICU=Tetanus; Respiratory failure; Severe ↑ ICP

Question 12

Before administering muscle relaxant it is essential to:

Answer 12

Assess the airway
Be competent in airway management
Have necessary equipment

Question 13

Suxamethonium

Answer 13

Physical properties: 2 ACH molecules, dose 1-2mg/ml and stored in fridge (Ampoules 100mg/2ml)

Question 14

What does Suxamethonium do?

Answer 14

Profound paralysis (60s)
Ultra-short acting
Causes fasciculations
Lasts 5 minutes

Question 15

How is Suxamethonium metabolized?

Answer 15

Metabolised by pseudocholinesterase aka plasma cholinesterase
synthesised in liver
Found freely in plasma
Markedly decreased in   SCOLINE APNOEA
No reversal

Question 16

SCOLINE APNOEA

Answer 16

Inherited homozygous or heterozygous
Prolonged paralysis
Supportive treatment with ventilation + sedation
FFPs

Question 17

Suxamethonium Side-Effects “BATH MASH”

Answer 17

Bradycardia
Anaphylaxis
Triggers MH
Histamine release
Muscle pain
Arrhythmia
Scoline Apnoea
Hyperkalemia

Question 18

Suxamethonium Contra-indication R-MUD

Answer 18

Drug allergy
Scoline apnoea
MH
Unknown myopathies
Risk of hyperkalaemia (Renal failure 
Paralysis
Crush / Burn injury)

Question 19

Non-depolarising agents

Answer 19

Benzylisoquinolines
Curare-based: atracurium, cisatracurium

Aminosteroids
Pancuronium, vecuronium, and rocuronium

Doses: based on lean body mass
Physical properties:
2 – 5ml ampoules
May require refrigeration

Question 20

Pharmacology of non-depolarisers

1) Clinical Effects
2) Metabolism
3) Excretion

Answer 20

Clinical effects:
Marked paralysis in 1 – 5 minutes (take longer to act)
No fasciculations
Duration is variable
Short-acting
Intermediate-acting
Long-acting

Metabolism:
Hepatic
Hoffman degradation

Excretion:
Renal
Hepatobiliary

Question 21

Vecuronium

Answer 21

Powder that must be mixed with water
Cardiovascularly stable
No histamine release
Intermediate-acting
Largely hepato-biliary excretion therefore safe in renal failure, but avoid in hepatic disease.

Question 22

Rocuronium

Answer 22

Most commonly used non-depolariser
Solution kept in fridge (50mg in 5mL)
Cardiovascularly stable
High dose: 1mg/kg can provide intubating conditions within 1 minute
Modified RSI
Intermediate duration of action
The higher the dose, the longer the paralysis

Question 23

Atracurium

Answer 23

Kept in Fridge
Histamine releasing
Increased risk of anaphylaxis
Hoffman degradation=
Spontaneous degradation=> breaks up into inactive molecules
Dependent on pH and temperature
Potentially toxic metabolite: laudanosine
Safe in renal and liver failure
Intermediate duration of action

Question 24

Reversal of non-depolarising agents

Answer 24

ALL NMDR’s should be reversed even if it has worn-off clinically.
NMDRs compete with Ach
So to reverse NMDR, increase Ach, so inhibit AchE.

Question 25

Drugs used for reversal AchE inhibitor/ Anticholinergic inhibitor AND their doses

Answer 25

``` Neostigmine= Acetylcholinesterase inhibitor Increases Ach concentration in synaptic cleft Ach COMPETES with NDMR But Ach ↑es at both nicotinic and muscarinic receptors which can cause side-effects Anticholinergic agent= Specifically an ANTI-MUSCARINIC agent Atropine or glycopyrrolate Given to prevent muscarinic effects (the B’s) Bronchial secretions Bronchospasm Bradycardia “B”eristalsis (peristalsis) ``` Neostigmine 2.5 mg + Glycopyrrolate 0.4–0.6 mg Neostigmine 2.5 mg + Atropine 1 mg

Question 26

When is it safe to reverse?

Answer 26

Check readiness with a peripheral nerve stimulator (TRAIN OF FOUR) At least 3 twitches should be present If a patient is already breathing adequately, it is generally safe to administer muscle relaxant Beware the patient with compromised liver or kidney function

Question 27

Signs of inadequate reversal

Answer 27

``` 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 ```

Question 28

Management of Inadequate Reversal

Answer 28

``` 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) ```

Question 29

Sugammadex

Answer 29

Reverse rocuronium Selective Relaxant Binding Agent NO muscarinic side-effects VERY EXPENSIVE