Muscle Relaxants Dr Rafiei Muscle Relaxants n What

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Muscle Relaxants Dr Rafiei

Muscle Relaxants Dr Rafiei

Muscle Relaxants n What are they used for? Facilitate intubation of the trachea n

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

Muscle Relaxants n How skeletal muscle relaxation can be achieved? n n n High

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

Muscle Relaxants n n Muscle relaxants must not be given without adequate dosage of

Muscle Relaxants n n 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 n How do they work? n Neuromuscular junction n n n Nerve

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

Neuromuscular Junction (NMJ)

Neuromuscular Junction (NMJ)

Binding of Ach to receptors on muscle end-plate

Binding of Ach to receptors on muscle end-plate

Muscle Relaxants n Depolarizing muscle relaxant n n Succinylcholine Nondepolarizing muscle relaxants n n

Muscle Relaxants n Depolarizing muscle relaxant n n Succinylcholine Nondepolarizing muscle relaxants n n n Short acting Intermediate acting Long acting

Depolarizing Muscle Relaxant n n Succinylcholine What is the mechanism of action? n n

Depolarizing Muscle Relaxant n n Succinylcholine What is the mechanism of action? n n n 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 n Succinylcholine n What is the clinical use of succinylcholine? n

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

Depolarizing Muscle Relaxant n Succinylcholine n What is phase I neuromuscular blockade? n What

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

Depolarizing Muscle Relaxant n Succinylcholine n Does it has side effects? n n n

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

Nondepolarizing Muscle Relaxants n What is the mechanism of action? n n n Compete

Nondepolarizing Muscle Relaxants n What is the mechanism of action? n n n 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 n Long acting n n Intermediate acting n n n Pancuronium

Nondepolarizing Muscle Relaxants n Long acting n n Intermediate acting n n n Pancuronium Atracurium Vecuronium Rocuronium Cisatracurium Short acting n Mivacurium

Nondepolarizing Muscle Relaxants n Pancuronium n n n Aminosteroid compound Onset 3 -5 minutes,

Nondepolarizing Muscle Relaxants n Pancuronium n n n 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 n Vecuronium n n n Analogue of pancuronium much less vagolytic

Nondepolarizing Muscle Relaxants n Vecuronium n n n 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 n Atracurium n Metabolized by n n n Ester hydrolysis Hofmann

Nondepolarizing Muscle Relaxants n Atracurium n Metabolized by n n n Ester hydrolysis Hofmann elimination Onset 3 -5 minutes, duration 25 -35 minutes Intubating dose 0. 5 mg/kg Side effects : n n histamine release causing hypotension, tachycardia, bronchospasm Laudanosine toxicity

Nondepolarizing Muscle Relaxants n Cisatracurium n n n Isomer of atracurium Metabolized by Hofmann

Nondepolarizing Muscle Relaxants n Cisatracurium n n n 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 n Rocuronium n n n Analogue of vecuronium Rapid onset 1

Nondepolarizing Muscle Relaxants n Rocuronium n n n 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 n n n Temperature Acid-base balance Electrolyte abnormality Age Concurrent diseases

Alteration of responses n n n Temperature Acid-base balance Electrolyte abnormality Age Concurrent diseases Drug interactions

Alteration of responses n Concurrent diseases n n Neurologic diseases Muscular diseases n n

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

Alteration of responses n Drug interactions n n n n Inhalation agents Intravenous anesthetics

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

Monitoring Neuromuscular Function n What are the purposes of monitoring? n n Administer additional

Monitoring Neuromuscular Function n What are the purposes of monitoring? n n Administer additional relaxant as indicated Demonstrate recovery

Monitoring Neuromuscular Function How to monitor? n n Clinical signs Use of nerve stimulator

Monitoring Neuromuscular Function How to monitor? n n Clinical signs Use of nerve stimulator

Monitoring Neuromuscular Function n Clinical signs n Signs of adequate recovery n n Sustained

Monitoring Neuromuscular Function n Clinical signs n Signs of adequate recovery n n Sustained head lift for 5 seconds Lift the leg (child) Ability to generate negative inspiratory pressure at least 25 cm. H 2 O, able to swallow and maintain a patent airway Other crude tests : tongue protrusion, arm lift, hand grip strength

Monitoring Neuromuscular Function n Use of nerve stimulator n n n Single twitch :

Monitoring Neuromuscular Function n Use of nerve stimulator n n n 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

Evoked responses during depolarizing and nondepolarizing block

Hierarchy of Neuromuscular Blockade Fraction of receptor occupied by nondepolarizing muscle relaxant Response to

Hierarchy of Neuromuscular Blockade Fraction of receptor occupied by nondepolarizing muscle relaxant 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 99 -100

Antagonism of Neuromuscular Blockade Effectiveness of anticholinesterases depends on the degree of recovery present

Antagonism of Neuromuscular Blockade Effectiveness of anticholinesterases depends on the degree of recovery present when they are administered n Anticholinesterases n n n Neostigmine n Onset 3 -5 minutes, elimination halflife 77 minutes n Dose 0. 04 -0. 07 mg/kg Pyridostigmine Edrophonium

Antagonism of Neuromuscular Blockade n What is the mechanism of action? n n n

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

Antagonism of Neuromuscular Blockade n Muscarinic side effects are minimized by anticholinergic agents n

Antagonism of Neuromuscular Blockade n Muscarinic side effects are minimized by anticholinergic agents n Atropine n n n Dose 0. 01 -0. 02 mg/kg Scopolamine glycopyrrolate

Reversal of Neuromuscular Blockade n Goal : re-establishment of spontaneous respiration and the ability

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