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Muscle Relaxants

Muscle Relaxants. Muscle Relaxants. What are they used for? Facilitate intubation of the trachea Facilitate mechanical ventilation Optimized surgical working conditions. Muscle Relaxants. How skeletal muscle relaxation can be achieved? High doses of volatile anesthetics

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Muscle Relaxants

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  1. Muscle Relaxants

  2. Muscle Relaxants • What are they used for? • Facilitate intubation of the trachea • Facilitate mechanical ventilation • Optimized surgical working conditions

  3. Muscle Relaxants • How skeletal muscle relaxation can be achieved? • High doses of volatile anesthetics • Regional anesthesia • Administration of neuromuscular blocking agents • Proper patient positioning on the operating table

  4. Muscle Relaxants • Muscle relaxants must not be given without adequate dosage of analgesic and hypnotic drugs • Inappropriately given : a patient is paralyzed but not anesthetized

  5. Muscle Relaxants • How do they work? • Neuromuscular junction • Nerve terminal • Motor endplate of a muscle • Synaptic cleft • Nerve stimulation • Release of Acetylcholine (Ach) • Postsynaptic events

  6. Neuromuscular Junction (NMJ)

  7. Binding of Ach to receptors on muscle end-plate

  8. Muscle Relaxants • Depolarizing muscle relaxant • Succinylcholine • Nondepolarizing muscle relaxants • Short acting • Intermediate acting • Long acting

  9. Depolarizing Muscle Relaxant • Succinylcholine • What is the mechanism of action? • Physically resemble Ach • Act as acetylcholine receptor agonist • Not metabolized locally at NMJ • Metabolized by pseudocholinesterase in plasma • Depolarizing action persists > Ach • Continuous end-plate depolarization causes muscle relaxation

  10. Depolarizing Muscle Relaxant • Succinylcholine • What is the clinical use of succinylcholine? • Most often used to facilitate intubation • What is intubating dose of succinylcholine? • 1-1.5 mg/kg • Onset 30-60 seconds, duration 5-10 minutes

  11. Depolarizing Muscle Relaxant • Succinylcholine • What is phase I neuromuscular blockade? • What is phase II neuromuscular blockade? • Resemble blockade produced by nondepolarizing muscle relaxant • Succinylcholine infusion or dose > 3-5 mg/kg

  12. Depolarizing Muscle Relaxant • Succinylcholine • Does it has side effects? • Cardiovascular • Fasciculation • Muscle pain • Increase intraocular pressure • Increase intragastric pressure • Increase intracranial pressure • Hyperkalemia • Malignant hyperthermia

  13. Nondepolarizing Muscle Relaxants • What is the mechanism of action? • Compete with Ach at the binding sites • Do not depolarized the motor endplate • Act as competitive antagonist • Excessive concentration causing channel blockade • Act at presynaptic sites, prevent movement of Ach to release sites

  14. Nondepolarizing Muscle Relaxants • Long acting • Pancuronium • Intermediate acting • Atracurium • Vecuronium • Rocuronium • Cisatracurium • Short acting • Mivacurium

  15. Nondepolarizing Muscle Relaxants • Pancuronium • Aminosteroid compound • Onset 3-5 minutes, duration 60-90 minutes • Intubating dose 0.08-0.12 mg/kg • Elimination mainly by kidney (85%), liver (15%) • Side effects : hypertension, tachycrdia, dysrhythmia,

  16. Nondepolarizing Muscle Relaxants • Vecuronium • Analogue of pancuronium • much less vagolytic effect and shorter duration than pancuronium • Onset 3-5 minutes duration 20-35 minutes • Intubating dose 0.08-0.12 mg/kg • Elimination 40% by kidney, 60% by liver

  17. Nondepolarizing Muscle Relaxants • Atracurium • Metabolized by • Ester hydrolysis • Hofmann elimination • Onset 3-5 minutes, duration 25-35 minutes • Intubating dose 0.5 mg/kg • Side effects : • histamine release causing hypotension, tachycardia, bronchospasm • Laudanosine toxicity

  18. Nondepolarizing Muscle Relaxants • Cisatracurium • Isomer of atracurium • Metabolized by Hofmann elimination • Onset 3-5 minutes, duration 20-35 minutes • Intubating dose 0.1-0.2 mg/kg • Minimal cardiovascular side effects • Much less laudanosine produced

  19. Nondepolarizing Muscle Relaxants • Rocuronium • Analogue of vecuronium • Rapid onset 1-2 minutes, duration 20-35 minutes • Onset of action similar to that of succinylcholine • Intubating dose 0.6 mg/kg • Elimination primarily by liver, slightly by kidney

  20. Alteration of responses • Temperature • Acid-base balance • Electrolyte abnormality • Age • Concurrent diseases • Drug interactions

  21. Alteration of responses • Concurrent diseases • Neurologic diseases • Muscular diseases • Myasthenia gravis • Myasthenic syndrome (Eaton-Lambert synrome) • Liver diseases • Kidney diseases

  22. Alteration of responses • Drug interactions • Inhalation agents • Intravenous anesthetics • Local anesthetics • Neuromuscular locking drugs • Antibiotics • Anticonvulsants • Magnesium

  23. Monitoring Neuromuscular Function • What are the purposes of monitoring? • Administeradditional relaxant as indicated • Demonstrate recovery

  24. Monitoring Neuromuscular Function How to monitor? • Clinical signs • Use of nerve stimulator

  25. Monitoring Neuromuscular Function • Clinical signs • Signs of adequate recovery • Sustained head lift for 5 seconds • Lift the leg (child) • Ability to generate negative inspiratory pressure at least 25 cmH2O, able to swallow and maintain a patent airway • Other crude tests : tongue protrusion, arm lift, hand grip strength

  26. Monitoring Neuromuscular Function • Use of nerve stimulator • Single twitch : single pulse 0.2 msec • Tetanic stimulation • Train-of-four : series of 4 twitch, 0.2 msec long, 2 Hz frequency, administer every 10-15 seconds • Double burst stimulation • Post tetanic count

  27. Evoked responses during depolarizing and nondepolarizing block

  28. Hierarchy of Neuromuscular Blockade

  29. Antagonism of Neuromuscular Blockade Effectiveness of anticholinesterases depends on the degree of recovery present when they are administered • Anticholinesterases • Neostigmine • Onset 3-5 minutes, elimination halflife 77 minutes • Dose 0.04-0.07 mg/kg • Pyridostigmine • Edrophonium

  30. Antagonism of Neuromuscular Blockade • What is the mechanism of action? • Inhibiting activity of acetylcholineesterase • More Ach available at NMJ, compete for sites on nicotinic cholinergic receptors • Action at muscarinic cholinergic receptor • Bradycardia • Hypersecretion • Increased intestinal tone

  31. Antagonism of Neuromuscular Blockade • Muscarinic side effects are minimized by anticholinergic agents • Atropine • Dose 0.01-0.02 mg/kg • Scopolamine • glycopyrrolate

  32. Reversal of Neuromuscular Blockade • Goal : re-establishment of spontaneous respiration and the ability to protect airway from aspiration

  33. THANK YOU

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