Neuromuscular Blockade Drug

Question 1

what is the action of NMB drugs?

Answer 1

prevents muscle contraction by interfering with the transmission of an action potential from the nerve ending to the muscle
*also known as relaxants, paralytics, NM antagonists

Question 2

what are some uses of NMBs?

Answer 2

*facilitate endotracheal intubation
*allow balanced anesthesia without patient movement
may not have to use as much gas since NMB keeps
patient still, gas only needed for sedation; less gas
can be breathed off quicker, allowing to wake up and
move faster
-decrease muscle tone to provide appropriate operating conditions
(large abd/GI cases, esp during suturing, prevents
hernia and complication)
-alleviate muscle activity during ECT so induced seizure is localized to the desired area in the brain
-assist in controlled long-term vent patients in ICU (ARDS, increased peep)

Question 3

what is the site of function for NMBs?

Answer 3

at the junction between the nerve ending and muscle

Question 4

Describe normal NM function.

Answer 4

• impulse arrives at the motor nerve terminal
• Ca++ influx cause vesicles holding Ach to line up at the presynaptic membrane right across from the muscle
• vesicles rupture and release Ach which diffuses the short distance across the synaptic cleft to the postsynaptic or postjunctional nicotinic (cholinergic)muscle receptors
• Ach binds with 2 alpha sites on postjunctional receptors causing the opening of the ion channel
• Na+ and K+ ions move through the channel causing depolarization (Na+ moves inside the membrane increasing the membrane potential from rmp -90mV to threshold of -45mV)
• Action potential spreads over the surfaces of the muscle fibers causing contraction

Question 5

How is Ach action terminated?

Answer 5

• Ach either quickly diffuses away or is metabolized
• AChE waits right outside of the ACh receptors in the postjunctional membrane
• Hydrolyzes ACh rapidly, resulting in a short depolarization and a rapid repolarization of the muscle cells

Question 6

What role does Ca++ play in NM function and how does Magnesium compare?

Answer 6

• Ca++ influx causes the vesicle holding ACh to align, promoting ACh release
• Magnesium has the OPPOSITE effect of Ca++
• Ca++ toxemia treated with Mag sulfate
• if Ca++ is LOW, ACh cant release and results in muscle weakness
• if Mag is HIGH, it will mimic low Ca++ effects, causing muscle weakness
• if and OB patient is put on a Mag drip, expect the need for LESS NMB

Question 7

What is ACh?

Answer 7

• main neurotransmitter in NM function
• synthesized in the motor nerve ending by acetylation of choline which is controlled by choline acetylase enzyme
• rapidly hydrolyzed by AChE to acetic acid and choline
• choline is taken back into the nerve ending to be used to make more ACh

Question 8

Describe the prejunctional or presynaptic ACh receptors.

Answer 8

• located on the nerve ending
• affects the neurotransmitter release
• Ion channel opening allows the influx of Na+ and Ca++
• activation mobilizes additional ACh for subsequent release
• blockade of these receptors cause a decrease in the release of ACh resulting in the tetanic fade

Question 9

Describe extrajunctional or perijunctional ACh receptors.

Answer 9

• found throughout the muscle cell
• similar to what is found on fetal muscle cells, but as the cell matures, these receptors fade away
• play no role in NM contraction
• if the muscle is not being used, these receptors proliferate (come back)
• seen with damaged, diseased, or denervated muscle like with burns, paralysis, stroke, immobilization, and some muscular dystrophies
• these receptors allow channels to stay open 4x longer

Question 10

What effect does extrajunctional receptors have on NMBs?

Answer 10

• Ach or nondepolarizing NMBs may become “distracted” and bind to extrajunctional receptors rather than postjunctional receptors where their block is desired
• with the depolarizing agent SCh, ion channels are also opened at extrajunctional receptors causing Na+ and Ca++ to move in and K+ to move out; however since these ions channels stay open 4x longer, continued K+ efflux leads to severe hyperkalemia

Question 11

When should you be cautious of extrajunctional receptors and not use a depolarizing agent (SCh)?

Answer 11

• past the 48 hour mark of a severe burn
• usually avoided in pediatric patients, esp. males age 4 and under, due to a high risk of undiagnosed muscular dystrophy
• hyperkalemia can lead to asystole in these patients

Question 12

Describe postjuctional or postsynaptic receptors.

Answer 12

• located in the junctional folds of the muscle membrane aligned across from area where presynaptic vesicles release ACh
• made up of 5 linear protein subunits: 2 alpha, beta, delta, and epsilon which reach from extra- to intracellular and form a channel for Na+, K+, and Ca++ flow
• ACh must bind to the extracellular sites on the 2 alpha subunits causing the receptor to change and open a channel for cations (+ ions) to flow through
• Ca++ and Na+ influx as K+ effluxes creating a change in the transmembrane potential and depolarization occurs causing muscle contraction
• BOTH alpha subunits must be bound to ACh for action

Question 13

Where are the specific sites of action for NMB agents?

Answer 13

• The binding sites of the alpha subunits are the sites of action for both nondepolarizing and depolarizing agents
• SCh attaches to the alpha sites and mimic the action of ACh causing depolarization, BUT not metabolized as quickly so stay on receptor blocking repolarization or more depolarization
• nondepolarizing agents attach to one alpha subunit to prevent ACh from binding, thus preventing depolarization
• only need to block one, since both units must be bound to ACh for action

Question 14

Describe channel blockade.

Answer 14

• besides acting on alpha subunits, some drugs can physically block an open channel or a closed channel around the extracellular surface
• antibiotics, quinidine, tricyclic antidepressants, and naloxone
• local anesthetics have this MoA which blocks the Na+ channel, blocking sensory

Question 15

time from administration to maximum effect

Answer 15

onset time

Question 16

time from administration to 25% recovery of twitch response

Answer 16

clinical duration

Question 17

time from administration to 90% recovery of twitch response (without reversal)

Answer 17

total duration

Question 18

time from 25% to 75% recovery of twitch response

Answer 18

recovery index (usually take more time to receive the first 25% twitch, but reach 75% quicker once 25% is achieved)

Question 19

the dose needed to produce 95% suppression of single twitch response (potency)

Answer 19

ED95 (effective dose)

Question 20

usually 2-3 times the ED95

Answer 20

intubating dose

Question 21

What are the objectives of clinical monitoring of NMB?

Answer 21

• titration of dosage to desired effect
• monitor for unusual resistance or sensitivity or prolonged action of NMB
• evaluation of reversibility
• determine recovery from block in conjunction with clinical evaluation

Question 22

How does NMB monitoring work?

Answer 22

• electrical stimulation of the peripheral motor nerve to observe the muscular contractions in response
• adult muscles have one NMJ per muscle cell except with the extraocular and facial muscles which have multiple innevations
• always place the black lead over the nerve
• ensure that the lead does not become a pressure point

Question 23

What will you look for with ulnar nerve stimulation.

Answer 23

adduction of the thumb via the adductor pollicis brevis muscle
-located lateral to the flexor carpi ulnaris tendon and medial to the ulnar artery

Question 24

Describe monitoring of the posterior tibial nerve

Answer 24

• when stimulated, causes plantar flexion of the great toe
• may use with head cases and when arms are tucked
• located behind the medial maleous of the tibia and posteromedial to the p.t. artery

Question 25

Describe monitoring of the lateral popliteal (peroneal) nerve

Answer 25

• when stimulated, the foot will dorsiflex

- located behind the head of the fibula and around the neck of the fibula

Question 26

Describe facial nerve monitoring

Answer 26

• stimulation causes response in the orbicularis oculi or the frontalis muscles
• place electrodes close to the tragus of the ear, be careful not to directly stimulate the superficial face muscles

Question 27

What is significant about the orbicularis oculi muscle?

Answer 27

• small and rapidly moving muscle and highly vascularized similar to the laryngeal muscle
• a greater density of ACh receptors cause a less dense block, making this muscle recovery more rapidly than others
• reflects the onset of laryngeal muscle relaxation
• possible to OD relaxant and overestimate recovery if only looking at the OO

Question 28

In what order do muscles have onset of relaxation?

Answer 28

• first, small rapidly moving muscles that are highly vascularized: OO and laryngeal muscles
• second, the trunk and abdominal, and long muscles with mostly slow fibers such as the adductor pollicis
• final onset is the intercostal and diaphragm muscle which may be a concern with reflux patients and coughing

Question 29

in what order do muscles recover?

Answer 29

• diaphragm recovers first (it is very resistant to NMB)
• rapidly moving muscles (eyes and fingers) are next
• last to recover are long muscle

Question 30

What are the first signs of relaxation if NMB are given to a conscious patient?

Answer 30

• inability to focus vision or keep eyelids open causing double vision (rapidly moving muscles first)
• inability to swallow
• inability to phonate (speak)
• sometimes will need to give a small dose (1/10) for slight relaxation but this can possibly cause major effects with major diagnoses like myasthenia gravis
• hearing acuity is intensified as small muscles of the middle ear are relaxed

Question 31

Describe single twitch stimulus.

Answer 31

• may be ok to use for monitoring of onset not useful for recovery since return to control height does not mean complete recovery from blockade
• need to know the baseline before giving relaxant
• uses frequency between 0.1 Hz (1 stimulus every 10sec) and 4 Hz (4 stimuli every 1 sec)
• after the administration of a nondepolarizer, the amplitude of subsequent twitches decrease in magnitude as the frequency increases

Question 32

Describe train of four.

Answer 32

• useful for maintenance of NMB along with clinical signs of relaxation
• the delivery of four stimuli at a frequency of 2 Hz (four stimuli in 2 sec)
• technique relies on the reduction of ACh release with rapid rates of stimulation (wait 10-12 sec before repeating)
• produces a ratio of the fourth twitch to the first twitch
• with recovery, cant really tell the difference between a ratio of 1:1 and 1:0.6

Question 33

Describe TOF fade.

Answer 33

• with the initiation of blockade, all twitches decrease and disappear together due to decreasing release of ACh
• Twitch 1 returns gradually
• 2/4 means 90% block
• 3/4 means 80% block
• 4/4 means 70-75% block
• clinical relaxation requires 75-90% block

Question 34

a TOF of > 0.6 what do you look for?

Answer 34

• patient should be able to sustain headlift more than 3 seconds
• really want them to hold 5 seconds
• requires cooperation
• for babies, look for a leg lift for 5 seconds

Question 35

how does TOF present with NMB?

Answer 35

• with a depolarizing block (SCh), all four twitches are reduced
• with a nondepolarizing block, the TOF ratio decreases or fades and is inversely proportionate to the degree of block
• if TOF fade occurs during the administration of SCh, it is a sign of phase II block

Question 36

describe double-burst.

Answer 36

• used during maintenance phase
• gives two short bursts of three stimuli at a frequency of 50 Hz separated by 750ms
• each burst represents 1st twitch and 4th twitch
• amplifying allows to see the difference and ratio between the first and fourth twitch
• easier to detect fade than with TOF

Question 37

describe tetanic stimulation.

Answer 37

• used to assess recovery
• stimulation of 50 Hz to 100 Hz
• if no fade on TOF, check tetanus for 5 seconds
• HURTS- do not use if surgeon is still stitching
• must wait 10 minutes after stimulation to avoid false reading due to large stimulation and extreme release of ACh that may still be active
• USE LAST

Question 38

posttetanic twitch

Answer 38

• used to anticipate how long before patient is reversible
• must have 1 twitch to be reversed
• 5 second 50 Hz tetanus, then 3 second pause, then twitch stimuli at 1 Hz (or just do TOF)
• after the tetanus stimulation, there is an increase in mobilization of ACh which allows increase in the twitch response
• if tetanic stimulation elicits no response, the posttetanic twitch might be elicited to estimate time until reversible
• posttetanic twitch of 10 coincides with first twitch TOF
• posttetanic of 1 means average time to first twitch of TOF for a long acting blocker of 30 min and 8 min for an intermediate blocker

Question 39

what are the guidelines for reversal of NMB?

Answer 39

• if no twitch, do not attempt reversal b/c antagonism will be difficult, potentially prolonged, and unpredictable
• with only one twitch in TOF, adequate reversal may take as long as 30 min
• with 2-3 twitches, reversal may take from 4-12 minutes based on the relaxant
• with 4 twitches, recovery can be achieved within 5 min (neostigmine) or 2-3 min (edrophonium)
• if no fade of twitches, 70-75% receptors blocked (only 70% block is fully recovered)

Question 40

what are some considerations of clinical monitoring?

Answer 40

• assess baseline after induction, but before NMB
• do not intubate until twitch is essentially absent
• after SCh, check recovery prior to giving a nondepolarizing NMB
• maintain 1-2 twitches during the case
• avoid using nerve stimulator on paralyzed limb
• peripheral muscles have a denser block than those monitored at the facial nerve
• don’t reverse unless you have one twitch
• use TOF (double burst) and sustained tetanus (in that order) to assess fade after reversal

Question 41

what are some conditions for nerve stimulation?

Answer 41

• 0.2 ms rectangular pulse
• firmly place moist electrodes on clean, dry, defatted, warm skin
• ulnar nerve stimulation, abduct the thumb to feel the adductor pollicis twitch
• negative (black) lead is placed directly over the nerve