4th year Anaesthesia MBChB Muscle Relaxants 4th year Anaesthesia MBChB

Triad of Anaesthesia Hypnosis Analgesia Muscle Relaxation

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)

Terminal axon of motor nerve Physiology Terminal axon of motor nerve

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

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

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

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

Neuromuscular Blockers 2 types Depolarisers Non-depolarisers

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

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

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!!!

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

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

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

Specific Muscle Relaxants

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

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

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

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

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 0.4-0.6mg

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

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”

This is how our patients feel when they are partially reversed

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

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

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

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

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

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