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 endplate

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 2035 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 10-15 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

No response

Whole body signs

Flaccid, extreme
relaxation

95

Posttetanic facilitation Diaphragm moves,

present
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