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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 Regional anesthesia Administration of neuromuscular blocking agents Proper patient positioning on the operating table 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 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 Neuromuscular Junction (NMJ) Binding of Ach to receptors on muscle end-plate Muscle Relaxants Depolarizing muscle relaxant Succinylcholine Nondepolarizing muscle relaxants Short acting Intermediate acting Long acting 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 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 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 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 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 Nondepolarizing Muscle Relaxants Long acting Intermediate acting Pancuronium Atracurium Vecuronium Rocuronium Cisatracurium Short acting Mivacurium 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, 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 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 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 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 Alteration of responses Temperature Acid-base balance Electrolyte abnormality Age Concurrent diseases Drug interactions Alteration of responses Concurrent diseases Neurologic diseases Muscular diseases Myasthenia gravis Myasthenic syndrome (Eaton-Lambert synrome) Liver diseases Kidney diseases Alteration of responses Drug interactions Inhalation agents Intravenous anesthetics Local anesthetics Neuromuscular locking drugs Antibiotics Anticonvulsants Magnesium Monitoring Neuromuscular Function What are the purposes of monitoring? Administer additional relaxant as indicated Demonstrate recovery Monitoring Neuromuscular Function How to monitor? Clinical signs Use of nerve stimulator 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 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 1015 seconds Double burst stimulation Post tetanic count Evoked responses during depolarizing and nondepolarizing block Hierarchy of Neuromuscular Blockade Fraction of receptor occupied by nondepolarizing muscle relaxant 99-100 Response to nerve stimulator Whole body signs No response Flaccid, extreme relaxation 95 Posttetanic facilitation present Diaphragm moves, hiccough possible 90 One of four twitch of TOF present Abdominal relaxation adequate for most prcedure 75 Four twitch of TOF present, TOF ratio 0.7 Tidal volume and vital capacity normal 50 100-Hz tetanus sustained Passes inspiratory pressure test 30 200-Hz tetanus sustained Head lift and hand-grip sustained 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 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 Antagonism of Neuromuscular Blockade Muscarinic side effects are minimized by anticholinergic agents Atropine Dose 0.01-0.02 mg/kg Scopolamine glycopyrrolate Reversal of Neuromuscular Blockade Goal : re-establishment of spontaneous respiration and the ability to protect airway from aspiration