Overview Of Neuromuscular Blockade & Specific NMDRs Flashcards
The Neuromuscular Junction (NMJ) in Skeletal Muscle
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)
Ach release blockers (BAM)
Botox
Aminoglycoside
Magnesium
(tubocurarine= block NMJ from binding to ACH receptor)
How is Muscle Relaxation Achieved
Blocking Motor Nerves= local anaesthetics
Blocking The NMJ= IV muscle relaxants (neuromuscular blockers
Blocking receptors inside cells= Dantrolene
Classification of Neuromuscular Blockers
A) Depolarising=> Suxamethonium
B) Non-depolarising=> all other muscle relaxants
Depolarising agent
Non-competitive action
Cannot be reversed… wear off / are metabolised over time
Non-depolarisers
Competitive inhibition
Compete with Ach for nicotinic receptors
Require reversal
ED95
“Effective Dose”
Dose of muscle relaxant that will paralyse 95% of normal people
Usual intubating does: 2 x ED95
Adequate paralysis
Adequate dose of muscle relaxant will result in:
Inability to breathe
Inability to maintain an airway
Loss of protective reflexes
Consciousness is completely unimpaired!!!
Factors that potentiate muscle relaxants
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
Some clinical examples where muscle relaxants are used
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
Before administering muscle relaxant it is essential to:
Assess the airway
Be competent in airway management
Have necessary equipment
Suxamethonium
Physical properties: 2 ACH molecules, dose 1-2mg/ml and stored in fridge (Ampoules 100mg/2ml)
What does Suxamethonium do?
Profound paralysis (60s)
Ultra-short acting
Causes fasciculations
Lasts 5 minutes
How is Suxamethonium metabolized?
Metabolised by pseudocholinesterase aka plasma cholinesterase synthesised in liver Found freely in plasma Markedly decreased in SCOLINE APNOEA No reversal
SCOLINE APNOEA
Inherited homozygous or heterozygous
Prolonged paralysis
Supportive treatment with ventilation + sedation
FFPs
Suxamethonium Side-Effects “BATH MASH”
Bradycardia Anaphylaxis Triggers MH Histamine release Muscle pain Arrhythmia Scoline Apnoea Hyperkalemia
Suxamethonium Contra-indication R-MUD
Drug allergy Scoline apnoea MH Unknown myopathies Risk of hyperkalaemia (Renal failure Paralysis Crush / Burn injury)
Non-depolarising agents
Benzylisoquinolines
Curare-based: atracurium, cisatracurium
Aminosteroids
Pancuronium, vecuronium, and rocuronium
Doses: based on lean body mass
Physical properties:
2 – 5ml ampoules
May require refrigeration
Pharmacology of non-depolarisers
1) Clinical Effects
2) Metabolism
3) Excretion
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
Vecuronium
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.
Rocuronium
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
Atracurium
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
Reversal of non-depolarising agents
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.
Drugs used for reversal
AchE inhibitor/
Anticholinergic inhibitor AND their doses
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
When is it safe to reverse?
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
Signs of inadequate reversal
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
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)
Sugammadex
Reverse rocuronium
Selective Relaxant Binding Agent
NO muscarinic side-effects
VERY EXPENSIVE
