Muscle Relaxants

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Muscle Relaxants
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Muscle Relaxants

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

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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

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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

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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

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Neuromuscular Junction (NMJ)
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Binding of Ach to receptors on muscle end-plate
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Muscle Relaxants

• Depolarizing muscle relaxant
• Succinylcholine
• Nondepolarizing muscle relaxants
• Short acting
• Intermediate acting
• Long acting

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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 gt Ach
• Continuous end-plate depolarization causes muscle
  relaxation

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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

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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 gt 3-5 mg/kg

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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

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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

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Nondepolarizing Muscle Relaxants

• Long acting
• Pancuronium
• Intermediate acting
• Atracurium
• Vecuronium
• Rocuronium
• Cisatracurium
• Short acting
• Mivacurium

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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,

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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

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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

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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

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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

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Alteration of responses

• Temperature
• Acid-base balance
• Electrolyte abnormality
• Age
• Concurrent diseases
• Drug interactions

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Alteration of responses

• Concurrent diseases
• Neurologic diseases
• Muscular diseases
• Myasthenia gravis
• Myasthenic syndrome (Eaton-Lambert synrome)
• Liver diseases
• Kidney diseases

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Alteration of responses

• Drug interactions
• Inhalation agents
• Intravenous anesthetics
• Local anesthetics
• Neuromuscular locking drugs
• Antibiotics
• Anticonvulsants
• Magnesium

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Monitoring Neuromuscular Function

• What are the purposes of monitoring?
• Administer additional relaxant as indicated
• Demonstrate recovery

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Monitoring Neuromuscular Function

• How to monitor?
• Clinical signs
• Use of nerve stimulator

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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

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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

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Evoked responses during depolarizing and
nondepolarizing block
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Hierarchy of Neuromuscular Blockade
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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

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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

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Antagonism of Neuromuscular Blockade

• Muscarinic side effects are minimized by
  anticholinergic agents
• Atropine
• Dose 0.01-0.02 mg/kg
• Scopolamine
• glycopyrrolate

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Reversal of Neuromuscular Blockade

• Goal re-establishment of spontaneous
  respiration and the ability to protect airway
  from aspiration

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