Transcript Muscle Relaxants

Muscle Relaxants
Muscle Relaxants
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What are they used for?
Facilitate intubation of the
trachea
 Facilitate mechanical
ventilation
 Optimized surgical working
conditions
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Muscle Relaxants
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How skeletal muscle relaxation can be
achieved?
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High doses of volatile anesthetics
Regional anesthesia
Administration of neuromuscular
blocking agents
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Proper patient positioning on the
operating table
Muscle Relaxants
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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
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How do they work?
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Neuromuscular junction
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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
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Depolarizing muscle relaxant
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Succinylcholine
Nondepolarizing muscle relaxants
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Short acting
Intermediate acting
Long acting
Depolarizing Muscle
Relaxant
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Succinylcholine
What is the mechanism of action?
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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
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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
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Succinylcholine
 What is phase I neuromuscular
blockade?
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What is phase II neuromuscular
blockade?
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Resemble blockade produced by
nondepolarizing muscle relaxant
Succinylcholine infusion or dose > 3-5 mg/kg
Depolarizing Muscle
Relaxant
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Succinylcholine
 Does it has side effects?
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Cardiovascular
Fasciculation
Muscle pain
Increase intraocular pressure
Increase intragastric pressure
Increase intracranial pressure
Hyperkalemia
Malignant hyperthermia
Nondepolarizing Muscle
Relaxants
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What is the mechanism of action?
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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
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Long acting
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Intermediate acting
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Pancuronium
Atracurium
Vecuronium
Rocuronium
Cisatracurium
Short acting
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Mivacurium
Nondepolarizing Muscle
Relaxants
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Pancuronium
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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
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Vecuronium
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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
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Atracurium
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Metabolized by
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Ester hydrolysis
Hofmann elimination
Onset 3-5 minutes, duration 25-35 minutes
Intubating dose 0.5 mg/kg
Side effects :
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histamine release causing hypotension,
tachycardia, bronchospasm
Laudanosine toxicity
Nondepolarizing Muscle
Relaxants
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Cisatracurium
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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
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Rocuronium
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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
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Temperature
Acid-base balance
Electrolyte abnormality
Age
Concurrent diseases
Drug interactions
Alteration of responses
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Concurrent diseases
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Neurologic diseases
Muscular diseases
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Myasthenia gravis
Myasthenic syndrome (Eaton-Lambert
synrome)
Liver diseases
Kidney diseases
Alteration of responses
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Drug interactions
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Inhalation agents
Intravenous anesthetics
Local anesthetics
Neuromuscular locking drugs
Antibiotics
Anticonvulsants
Magnesium
Monitoring Neuromuscular
Function
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What are the purposes of monitoring?
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Administer additional relaxant as
indicated
Demonstrate recovery
Monitoring Neuromuscular
Function
How to monitor?
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Clinical signs
Use of nerve stimulator
Monitoring Neuromuscular
Function
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Clinical signs
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Signs of adequate recovery
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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
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Use of nerve stimulator
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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
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Anticholinesterases
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Neostigmine
 Onset 3-5 minutes, elimination halflife 77
minutes
 Dose 0.04-0.07 mg/kg
Pyridostigmine
Edrophonium
Antagonism of
Neuromuscular Blockade
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What is the mechanism of action?
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Inhibiting activity of acetylcholineesterase
More Ach available at NMJ, compete for
sites on nicotinic cholinergic receptors
Action at muscarinic cholinergic receptor
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Bradycardia
Hypersecretion
Increased intestinal tone
Antagonism of
Neuromuscular Blockade
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Muscarinic side effects are minimized by
anticholinergic agents
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Atropine
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Dose 0.01-0.02 mg/kg
Scopolamine
glycopyrrolate
Reversal of Neuromuscular
Blockade
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Goal : re-establishment of
spontaneous respiration and the
ability to protect airway from
aspiration