Neuromuscular Blockade Drug Flashcards
what is the action of NMB drugs?
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
what are some uses of NMBs?
*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)
what is the site of function for NMBs?
at the junction between the nerve ending and muscle
Describe normal NM function.
- 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
How is Ach action terminated?
- 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
What role does Ca++ play in NM function and how does Magnesium compare?
- 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
What is ACh?
- 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
Describe the prejunctional or presynaptic ACh receptors.
- 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
Describe extrajunctional or perijunctional ACh receptors.
- 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
What effect does extrajunctional receptors have on NMBs?
- 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
When should you be cautious of extrajunctional receptors and not use a depolarizing agent (SCh)?
- 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
Describe postjuctional or postsynaptic receptors.
- 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
Where are the specific sites of action for NMB agents?
- 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
Describe channel blockade.
- 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
time from administration to maximum effect
onset time
time from administration to 25% recovery of twitch response
clinical duration
time from administration to 90% recovery of twitch response (without reversal)
total duration
time from 25% to 75% recovery of twitch response
recovery index (usually take more time to receive the first 25% twitch, but reach 75% quicker once 25% is achieved)
the dose needed to produce 95% suppression of single twitch response (potency)
ED95 (effective dose)
usually 2-3 times the ED95
intubating dose
What are the objectives of clinical monitoring of NMB?
- 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
How does NMB monitoring work?
- 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
What will you look for with ulnar nerve stimulation.
adduction of the thumb via the adductor pollicis brevis muscle
-located lateral to the flexor carpi ulnaris tendon and medial to the ulnar artery
Describe monitoring of the posterior tibial nerve
- 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
Describe monitoring of the lateral popliteal (peroneal) nerve
- when stimulated, the foot will dorsiflex
- located behind the head of the fibula and around the neck of the fibula
Describe facial nerve monitoring
- 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
What is significant about the orbicularis oculi muscle?
- 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
In what order do muscles have onset of relaxation?
- 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
in what order do muscles recover?
- diaphragm recovers first (it is very resistant to NMB)
- rapidly moving muscles (eyes and fingers) are next
- last to recover are long muscle
What are the first signs of relaxation if NMB are given to a conscious patient?
- 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
Describe single twitch stimulus.
- 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
Describe train of four.
- 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
Describe TOF fade.
- 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
a TOF of > 0.6 what do you look for?
- 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
how does TOF present with NMB?
- 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
describe double-burst.
- 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
describe tetanic stimulation.
- 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
posttetanic twitch
- 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
what are the guidelines for reversal of NMB?
- 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)
what are some considerations of clinical monitoring?
- 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
what are some conditions for nerve stimulation?
- 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
