Transcript Relax and Breath ALANA

Everyone Relax and
Breath:
Review of Neuromuscular
Relaxants
Timothy Finn, CRNA MSN, PhDc
Sedation Scale to Lecturing
Attentive
Interested
Good
Need
Review
more
Following Coffee
When is
the next
break
Will
anyone
notice if I
leave?
When
will he
shut
up?
Stage 4 of
anesthesia
ZZZZZZZ!
Jaw
Thrust!
Objectives

Review of current and future muscle relaxants

Explain the physiology and metabolism

Understand the different properties

Identify appropriate monitoring techniques

Emphasize the pro’s/con’s to reversing

Implications for practice
History of Muscle Relaxants
 Earliest known muscle relaxant Curare
 16th Century
 Natives in South America
 Amazon Basin
 Poison tipped arrows
 Ourare
 Poison tipped arrow
History of Muscle Relaxants
 Curare
 Active ingredient
 Tubocurarine chloride
 Jan 23, 1942
 Griffith and Johnson pioneered clinical introduction
 Tubocurarine chloride
 Montreal Homeopathic Hospital
 Present day
 Luxury and excuse for surgeons
I want Relaxation!!!!!
2 Types of Muscle Relaxants
NEUROMUSCULAR
BLOCKERS
(Peripherally)
SPASMOLYTICS
(Centrally)
Spasmolytic
 Reduce spasticity
 Enhance the level of inhibition
 Centrally acting
 Treatment of neuromuscular conditions
Spasmolytic
 Used to treat spasticity
 Increased muscle tone
 Combined with muscle weakness
 Centrally acting muscle relaxants
 Inhibit reflexes within the spinal cord or GABA receptors
Spasmolytic
Dantrolene
 Mechanism of Action
 Reduces skeletal muscle strength by interfering with
muscle excitation
 Interferes with calcium release through the sarcoplasmic
reticulum
 Cardiac and smooth muscles are depressed
Spasmolytic
Dantrolene
 1) Used for muscle spasticity
 2) Malignant hyperthermia
 Inability of sarcoplasmic reticulum to sequester calcium
 Rapid release of calcium with massive muscle
contraction, lactic acid production and increased body
temp.
Neuromuscular Blockade
 Interfere with motor end plate transmission
 No CNS activity
 Relaxes muscles
 Used for surgical procedures
 Used for ventilation
 Primary part of general anesthesia
Neuromuscular Junction
Neuromuscular Transmission
 1. Motor neuron depolarizes causing action potential
 2. Depolarization of neuron causes influx of Calcium
 3. Calcium influx triggers synaptic vesicles
 4. Release of Ach
 5. Ach diffuses across synaptic cleft and binds to post
synaptic nicotinic receptors. Ach causes influx of sodium and
out flux of K leading to depolarization of end plate
membrane (muscle contraction)
 5. Unbound Ach in synaptic cleft diffuses away and
hydrolyzed by AchE (anticholinesterase)
Neuromuscular Blockade
 Presynaptically:
Inhibit acetylcholine synthesis or release (practically
not used).
As they may have whole body unspecific nicotinic as
well as muscarinic effects
 Postsynaptically:
Block Receptor activity
Block ion channel at the end plate
They interfere with the post synaptic action of
acetylcholine.
Neuromuscular Blockade
 Drugs that relax skeletal muscle by interacting at the
neuromuscular junction
 1) Depolarizing
 Produce excessive depolarization of the motor end plate
causing excessive stimulation
 2) Nondepolarizing
 Prevents access of Ach to its receptors
 Prevents depolarization of the motor end plate
Neuromuscular Blockade
 Chemical breakdown
 All neuromuscular blockers resemble ACh molecule
 All are poorly lipid soluble
 Quaternary nitrogen
Depolarizing Neuromuscular
Blockade
Drug
Duration
Elimination
Succinylcholine
5-10 min
-Plasma
Cholinesterase
-Rapid
metabolism
Decamethonium
(Syncurine)
Depolarizing Neuromuscular
Blockade
 Mechanism of action
 Act like ACh
 Persist in higher concentration and longer duration of action
 Opens Na+ channels
 Leads to muscle contraction/twitching
Depolarizing Neuromuscular
Blockade
Adverse Effects
Results
Cardiac Arrest
Hyperkalemia due to drastic release
of K in cases of burns and trauma
Muscarinic effects of acetylcholine
resulting in bradycardia
Increased Intraocular Pressure
Contraction of ocular muscles
Increased Intragastric Pressure
Muscle fasiculations
Muscle Pain
Muscle contractions resulting in
myalgias
Malignant Hyperthermia
Various symptoms including muscles
rigidity
Non-Depolarizing
Neuromuscular Blockade
 Mechanism of action
 Act by blocking ACh receptors
 Key-in-hole Theory
 Combine with nicotinic receptors to prevent ACh binding
 Competitive blockers
 Prevent depolarization
 Inhibit muscle contraction
 Action is overcome by increasing ACh available at
receptor site.
Non-Depolarizing
Neuromuscular Blockade
 All receptors are not made equally
 All muscles are not equally sensitive
 Small rapidly contracting muscles are relaxed first
 Respiratory muscles
 Last to be affected
 First to recover
Non-Depolarizing
Neuromuscular Blockade
 Does not cross blood brain barrier (poorly lipid soluble)
 Limited volume of distribution
 Highly ionized
 Low lipophilicity
 Most metabolized by the liver, kidney, and plasma
 Organ insufficiency may affect metabolism
 Degraded spontaneously by ester hydrolysis
 (Cisatracurium)
NonDepolarizing
Neuromuscular Relaxants
NonDepolarizing
Neuromuscular Relaxants
Cisatracurium
 Isoquinoline
 Dosage
 0.05 – 0.1 mg/kg
 Onset 2.4 - 3.2 min
 Intermediate duration
 25 % recover 15-24 minutes
 Metabolized by Hoffman
elimination and ester hydrolysis
 Adverse effect
 Histamine release
 Bronchospasm
Drug Interactions
 Amikacin
 Tetracycline
 Capreomycin
 Tobramycin
 Clindamycin
 Minocycline
 Doxycycline
 Kanamycin
 Neomycin
 Streptomycin
Rocuronium
 Aminosteroid
 Dosage
 0.6 – 1.2 mg/kg
 Rapid onset
 0.4-6 minutes Avg < 2
minutes
 Intermediate duration
 25% recovery in 12 – 15
minutes
 Metabolized
 Hepatic (75-90%) and
Renal
 High allergic
risk/Anaphylaxis
 Particularly asthmatics
Drug Interactions
Vecuronium
 Aminosteroid
 Dosage
 0.08 – 0.1 mg/kg
 Onset
 2.5 – 3 minutes
 25% recovery
 25 – 40 min
 Metabolized
 Renal/Hepatic
 Adverse effects
 Histamine release
 Bronchospasm
 Caution in Hepatobiliary/Renal Issues
Drug Interactions
 Amikacin
 Tetracycline
 Capreomycin
 Tobramycin
 Clindamycin
 Minocycline
 Doxycycline
 Kanamycin
 Neomycin
 Streptomycin
Pancuronium
 Aminosteroid
 Dosage
 0.04 – 0.10 mg/kg
 Onset
 Short acting
 4.0-6.0 minutes
 25% recovery
 80–100 minutes
 Metabolism
 Enzymatic hydrolysis
 Renal/Hepatic
 Adverse effects
 Tachycardia
 Hypotension
 Wheezing
 Histamine
Mivacurium
 Benzylisoquinolinium
 Dosage
 0.07 – 0.10 mg/kg
 Onset
 Short acting
 2.0 – 7.6 minutes
 25% recovery
 8-24 min
 Metabolism
 Enzymatic hydrolysis
 Renal/Hepatic
 Adverse effects
 Bronchospasm
 Wheezing
 Histamine
Drug Interactions
 Amikacin
 Lincomycin
 Aminophylline
 Phenytoin
 Azathioprine
 Piperacillin
 Carbamazepine
 Theophylline
 Clindamycin
 Tobramycin
 Fosphenytoin
 Gentamicin
Measuring Muscle Relaxation
 Train of Four 4/4
 0/4 100% receptors blocked
 1/4 90% receptors blocked
 2/4 80% receptors blocked
 3/4 75 % receptors blocked
 4/4 0-75% receptors blocked
Ulnar Nerve
Facial Nerve
Posterior Tibial Nerve
Train of Four
 Adductor Pollicis-easily blocked
 Ulnar nerve monitoring beneficial for two main reasons:
 1. Ease of placement and access
 2. Ease of monitoring/accessibility
Train of Four
Redosing Muscles Relaxant

0/4
I
1/4
2/4
I
I
90%
Blocked
Induction
Dose
0/4
I
80%
blocked
100%
10% of Induction Dose
blocked
Incidence of Residual
Neuromuscular Blockade
25-35%Occurrence
Incidence of Residual
Neuromuscular Blockade
 Decreased respiratory muscles
 Decreased TV and cough reflex
 Decreased coordination of Laryngeal-Pharyngeal
musculature
 Increased risk of aspiration
 Increased cost of hospital and intensive care
Sensitivity of Muscles
 Diaphragm
 Larynx
 Adductor Muscles
 Head and Neck
 Pharynx (Swallowing reflexes)
 Extraocular Muscles
Most
Sensitive
To Reverse or Not To
That is the Question?
Neuromuscular Blockade
Reversal
 Mechanism of action
 Increasing concentration of acetylcholine in synaptic cleft
 Maximize muscarinic receptors
 Ex. Neostigmine, Physostigmine, Edrophonium
 Adverse effect
 Bradycardia, headache, blurred vision, nausea, vomiting,
abdominal cramps
 Muscarinic anticholinergics
 Atropine and Glycopyrolate
 Avoid muscarinic receptor effects
Sugammadex
Sugammadex
 Modified gamma-cyclodextrin
 Reversal of neuromuscular blockade
 Specific to aminosteroid neuromuscular blocking agents
 Rocuronium
 First selective relaxant binding agent
 Does not rely on inhibition of acetylcholinesterase
 Immediate reversal < 3 minutes
 Encapsulates the nondepolarizers
 Reversal dose = 2 - 4mg/kg
 Must have 1 – 2/4 twitches
Psuedocholinesterase
Deficiency
 Heterozygous atypical (1 abnormal gene) 1 in 50 patients
 Prolonged blockade 20-30 minutes after succinylcholine
 Homozygous atypical (2 abnormal gene) 1 in 3000 patient.
 Prolonged blockade 6-8 hours after succinylcholine
 Dibucaine number represents the percentage inhibition of
pseudocholinesterase activity
 Inhibits normal pseudocholinesterase by 80%,
 Heterozygous by 40-60% (atypical)
 Homozygous by 20% (atypical)
Dibucaine Number