NMBDs: Physiology/Succinylcholine (EXAM III) Flashcards
When did curare start to be used as a medical anesthetic?
1940
Which of the following is the newest NMBD?
A. Atracurium
B. Vecuronium
C. Pancuronium
D. Cistracurium
A. Atracurium (1980)
B. Vecuronium (1980)
C. Pancuronium (1960)
D. Cistracurium (1995)
Why was Rapacurium (Raplon) discontinued in 2001?
Massive laryngospasm and bronchospasm leading to death.
The effect of NMBD is to interrupt the transmission of nerve impulses at the _____.
Neuromuscular Junction (NMJ)
The MOA of NMBD is either depolarizing or non-depolarizing.
Deploarizing NMBD will _________ the action of ACh.
Non-depolarizing NMBD will ______ the action of ACh.
Deploarizing (Succs) NMBD will mimic the action of ACh.
Non-depolarizing NMBD will interfere with the action of ACh.
Purpose of NMBD for anesthesia.
- Decrease airway trauma
- Facilitate surgical exposure
- Minimize injury from patient movement (cant fall off the bed)
What classification of NMBD is Succinylcholine (Anectine)?
Depolarizing NMBD
Only depolarizing agent used in anesthesia.
Name a long-acting non-depolarizing NMBD.
Pancuronium (Pavulon) 60-90 min duration
Name a short-acting non-depolarizing NMBD.
Mivacurium (Mivacron)
Move a lot, short-acting
What is the chemical classification of Pancuronium?
Aminosteroid
What is the chemical classification of Mivacurium?
Benzylisoquinoline
What is the chemical classification of Pancuronium (Pavulon)?
Aminosteroid
Which intermediate-acting NMBDs are Benzylisoquinolines?
Atracurium (Tracrium)
Cisatracurium (Nimbex)
Which intermediate-acting NMBD are Aminosteroids?
Vecuronium (Nocuron)
Rocuronium (Zemuron)
Which 3 NMBDs are benzylisoquinolones?
Atricurium (tracrium)
Mivacurium (mivacron)
Cisatracurium (nimbex)
The rest are aminosteroids
Why would you use Pancuronium for a surgery?
Why would you NOT use it?
A surgery expected to last a while, instead of just redosing the patient a lot.
Not to be used in a surgery that is not expected to be a long surgery because it will last longer than the surgery.
What is ED95 in regards to NMBDs?
The potency of NMBD. The dose that is necessary to produce a 95% suppression of a single twitch in the presence of nitrous/ barbiturate/ opioid anesthesia.
What nerve is stimulated so that the adductor pollicis muscle will produce a single twitch at 1 Hz (thumb adduction)?
Ulnar nerve
The order of block for NMBD is dependent on:
- Number of presynaptic ACh-containing vesicles released.
- Number of ACh receptors.
- Blood Flow to the area.
- Drug potency
Why does the order of block depend on Ach receptors and vesicles?
Because these drugs mimic Ach
Low potency NMBD will onset _________ than higher potency NMBD.
Faster
Lower potency NMBD will have more molecules than higher potency NMBD. This will create a higher concentration gradient and result in a faster onset.
Small, rapidly moving muscles will be blocked ________ than large muscles.
Faster
Eyes will be paralyzed first before diaphragm.
What does this graph show?
- Both Larynx and Adductor Pollicis muscle received 0.5 mg/kg of Rocuronium.
- Both muscles experience a dramatic decrease in twitch percent height, but the adductor pollicis is completley blocked while the larynx got down to a twitch height of 20%.
- Both muscles recovered at the same rate. Almost 100% twitch response returned by minute 40.
What does this graph show in regards to recovery time of the larynx compared to the adductor pollicis muscle?
It shows that if you wait to intubate until you see the adductor pollicis muscle at 0 twitches, the larynx is already starting to reverse. You shouldn’t wait to see the thumb twitches gone.
Since reversal happens in the opposite direction, which muscle will return first?
The adductor pollicis will return before the central area returns.
Checking a twitch in which muscle will assess the diaphragm and laryngeal muscle blockade.
Orbicularis Oculi
If there are no twitches to the facial nerve, the diaphragm and laryngeal muscles are adequately blocked. Best indicator of intubating conditions.
The orbicularis oculi UNDERestimates _____________.
residual paralysis.
What is residual paralysis?
when a muscle-relaxing drug (a paralytic) given during surgery doesn’t fully wear off before the patient wakes up. This can cause weakness, trouble breathing, or difficulty moving.
Is checking a twitch in the adductor pollicis a good indicator for laryngeal relaxation?
No, it is not a good indicator of laryngeal relaxation.
Checking a twitch of the adductor pollicis is a good indicator or peripheral recovery.
Which muscle is the gold standard to check a twitch on for recovery?
Adductor pollicis (Ulnar Nerve)
What is the placement of electrodes on ulnar nerve?
What will the response be?
Red toward the head
What is a defasciculating dose of NMBD?
What symptoms will the patient experience with a defasciculating dose?
1/10th of intubating dose of a Nondepolarizer is given early (primer) to prevent fasciculation that is caused by a depolarizing NMB.
Blurred Vision (expected)
Mandibular weakness
Ptosis (droopy eyes)
Diplopia (double vision)
Dysphagia
Increased hearing acuity - people need to be quiet
Let patient know they might start to feel weak and get blurry vision. Encourage them to close their eyes.
What can solve the expected blurry vision caused by paralytics?
Having the patient close their eyes.
What are the buttons on a nerve stimulator in order from top left to bottom right?
DBS, Twitch, Tetany, TrainOfFour
A single twitch nerve stimulator starts at _____ Hz/second decreasing to ______ Hz/10 secs.
1 Hz/sec to 0.1 Hz/10 secs
With an onset of a block a single twitch will ______.
fade with each stimulus
Double burst stimulator is _____ short bursts followed by ______ short bursts.
The double burst stimulator setting uses ________ Hz
3, 3
50 Hz (supramaximal current)
Which 2 tests use supramaximal stimulation Hz?
The left two: DBS, and tetany
Why was the double burst stimulator developed?
Developed to improve detection of residual block (fade).
Fade in 2nd response vs 1st response.
Qualitatively better than TOF.
Train of Four is ________ stimuli at _______ Hz with ______ seconds between each burst.
4 stimuli at 2 Hz with ½ seconds between each burst
TOF reflects events at _________ membrane.
Presynaptic
Prior to NMBD what will be your twitches on the TOF?
What will be the TOF ratio before the paralytic (Twitch 4 : Twitch 1)?
4/4 twitches
Ratio 1
Experienced anesthetist are unable to qualitatively detect the fade of a TOF < ______.
0.4
The twitch will have to go from unblocked to completely blocked in order to tell a difference
There will be significant residual block with a TOF of ______ to _____.
0.7 to 0.9
You will not feel a fade, but there will still be blockade at the NMJ. Patient will still need reversal agent.
Tetanic stimulation is very rapid, it will be ________ Hz for _____ seconds.
50 Hz for 5 seconds
If a _____ NMBD is given, a tetanic stimulation will result in a sustained muscle response.
Depolarizing NMBD (Succinylcholine)
If a _____ NMBD is given, a tetanic stimulation will result in a non-sustained muscle response (fade).
Nondepolarizing NMBD (Roc/Vec/Panc/Cis)
The fade is a result of presynaptic depletion of ACh or inhibition of release
What is post-tetanic stimulation?
Single twitch 3 seconds after tetanic stimulation.
The post-tetanic stimulation will occur d/t accumulation of calcium during tetany, the excess calcium will stimulate ACh release.
No response in post-tetanic stimulation will mean ______.
intense blockade
What kind of blocks are in column A, B, and C?
What kind of nerve stimulation is performed in row 1 through 4?
A study performed showed that _____ % of patients that were not given anticholinesterase drugs for NMBD reversal and no use of nerve stimulator had post-op blockade once extubated.
42%
When no reversal is used, they patient is 42% likely to experience residual paralysis.
A study performed showed that less than ____ % of patients that were given anticholinesterase drugs for NMBD reversal and use of nerve stimulator had post-op blockade once extubated.
<4%
This shows how important it is to give a reversal agent.
The presynaptic motor neuron is large and _________ which helps with transmission of nerve impulses.
myelinated= FAST
The motor nerve ending is ________ and innervates single muscle fibers.
unmyelinated= not as fast
The presynaptic motor neuron is responsible for what three things involving ACh?
- ACh synthesis
- ACh uptake and storage in vesicles
- ACh release and uptake of choline
The synaptic cleft is _______ nm wide with fluid that contains ________ and _________.
20-50 nm
Collagen and acetylcholinesterase (plasma cholinesterase, butyrylcholinesterase)
ACh release is dependent on what electrolyte?
Calcium, it is the signal to release Ach
What does Acetylcholinesterase do to ACh?
Hydrolyze ACh to acetic acid and choline to be recycled
Post-synaptically, the membrane has multiple _______.
Post-synaptically, the resting membrane potential is _______.
Membrane potential is largely maintained by what two electrolytes?
folds
-90 mV
Na+ and K+ (sodium and potassium)
How many subunits are on a transmembrane nicotinic acetylcholine receptor (nAChR)?
Name them.
Five subunits. (Pentameric unit)
2 alphas, beta, delta, gamma
If NMBD (non-depolarizer) binds to nACh, there will be no __________ change and no ion flow.
conformational change
Succinylcholine only requires binding at one ________ subunit. It is postulated that this will cause ________ before total blockade.
one alpha subunit
fasciculation
_________ is the only depolarizing NMBD in clinical practice.
What are two unique characteristics of this drug?
What is this NMBD most useful for?
What is the downside of this NMBD?
- Succinylcholine
- Provides very intense and rapid paralysis
- Offsets of effects prior to hypoxia
- Rapid Sequence Induction
- Histamine Release (tachycardia, rash, welps)
What is the dose of Succinylcholine?
Onset:
Duration:
Dose: 1 mg/kg IV ACTUAL BODY WEIGHT
Onset: 30-60 seconds
Duration: 3-5 minutes
What is the MOA of succinylcholine (Sch)?
- Attaches to one or both alpha subunits of the nAChR.
- Mimics the effect of ACh, but has a sustained opening of the receptor channel (hydrolysis is slower than ACh).
SCh will cause how much increase in serum K+?
0.5 mEq/L
What type of drugs are phase I blocks?
Only depolarizing NMBDs. So just succinylcholine.
What are characteristics of a phase I block?
Decrease contraction to single twitch stimulation.
Decrease amplitude to continuous stimulation.
TOF ratio > 0.7 (NO FADE)
Absence of post-tetanic facilitation
Skeletal muscle fasciculation
Phase II Blocks are typical of ___________ NMBD.
non-depolarizing
How can a Phase I block transition to a Phase II block?
An overdose of succinylcholine, like using 2-4 mg/kg instead of the recommended 1 mg/kg
- Lack of/ poorly functioning pseudocholinesterase
Succinylcholine is hydrolyzed by __________.
Butyrylcholinesterase (plasma cholinesterase)
Is succs safe in hepatic or renal disease?
Yes, because it is metabolized in the plasma instead.
Because of the Succs dose being in actual body weight, what would happen if you accidentally gave an obese person a dose based on ideal body weight?
If given based on IBW, then the effects of the drug would be gone very fast due to an obese people having additional cholinesterase activity and therefore breaking the drug down faster at the postsynaptic cleft.
What factors can decrease pseudocholinesterase activity?
- Hepatic disease
- Drugs (neostigmine, reglan, chemo)
- Genetics
- CKD
- Estrogen (think pregnancy)
What factor can increase pseudocholinesterase activity?
What does this mean clinically?
- Obesity
- Higher dosing of succinylcholine is necessary for obese patients bc it will break down faster with more esterases present.
What does dibucaine number mean?
What does it mean in extremely simple terms?
Dibucaine number reflects the quality of the enzyme that inhibits the breakdown of butyrylcholinesterase.
- ↑ Dibucaine number = Fast succinylcholine metabolism
- ↓ Dibucaine number = Slow succinylcholine metabolism
What is normal dibucaine number?
80
More butyrylcholinesterase will stick around and break down Sch
What will a dibucaine number of 20 mean for Sch?
1 mg/kg of SCh will last 3 hours (this is GREATLY prolonged, as Succs has a duration of 3-5 mins)
Less butyrylcholinesterase will stick around
What are the side effects of Succinylcholine? This is why succs is considered a dirty drug!
- Cardiac dysrhythmias
- Hyperkalemia
- Myalgia
- Myoglobinuria
Fasciculations lead to: - ↑ Gastric pressure
- ↑ IOP
- ↑ ICP
- Masseter spasm
What is the pre-treatment to the side effects of SCh?
- Pre-treatment with non-depolarizing NMBD “like 1/10th of a normal dose”
This defasciculating dose either decreases, prevents, or mask the side effects of SCh.
What dysrhythmias can occur with succinylcholine administration?
- ↓HR (sinus brady)
- Junctional Rhythm
- Sinus Arrest
Cardiac dysrhythmia’s will usually present on the 1st dose of succinylcholine. T/F?
False. If dysrhythmias occur, it will be with the 2ⁿᵈ dose.
What are succinylcholine’s actions at the ANS ganglia?
- ↑HR
- mimic ACh
This usually occurs with large doses.
Because of this, the normal SB, JR, and sinus arrest are masked.
Patient’s with _________ sites will have true hyperkalemia when given SCh.
Extrajunctional NMJ sites (more ion channels)
What patient populations are more susceptible to the hyperkalemic effects of succinylcholine?
- Individuals with unrecognized muscular dystrophy (Duchenne’s)
- Unhealed 3rd degree burns
- Denervation of Skeletal Muscles (bed-ridden patients)
- Upper motor lesions
Who will experience myalgia with Sch?
Where will the myalgia be located?
Young adults
Neck, back, abdomen
Pediatric patients more frequently experience this with succinylcholine administration.
Myoglobinuria (damaged to skeletal muscles), usually found later to have MH or muscular dystrophy.
No succinylcholine for children
If myoglobinuria is seen in the foley, who should you let know?
Since myoglinuria is common, you should let the care team know about it when you transfer them so they can keep an eye on it
Sch will increase intragastric pressure and LES pressure, this will increase risk of _______.
Aspiration
This is related to the intensity of the fasciculation and the direct increase in vagal tone.
Sch will increase intraocular pressure _______ minutes (range) after administration and last _________ minutes (range).
2-4 minutes after admin
last 5-10 minutes
It peaks in the middle of the duration but returns to normal.
Sch will be an absolute contraindication in ______________ chamber injury.
open anterior
Succinylcholine will increase ICP transiently, how can this effect be attenuated?
By hyperventilating the patient, the PaCO2 will decrease leading to cerebral vasoconstriction. This will decrease CBF and decrease ICP before Succinylcholine administration.
So according to this, what is a good way to decrease ICP?
Hypervetilation=decreased CO2=less vasodilation=less blood flow= less space occupied
Sustained skeletal muscle contraction, incomplete jaw relaxation, and/or masseter muscle spasm d/t Sch could be an indication of what conditions?
Early indicator of Malignant Hyperthermia
Inadequate dosage given in children
What is the hereditary rhabdomyolysis associated with all volatile anesthetics and SCh?
Malignant Hyperthermia (MH)
If MH is untreated what can it lead to?
Muscle destruction
Hyperkalemia
Acidosis
Dysrhythmia
Renal Failure
DIC
MH causes mutations in what receptor that causes excessive calcium release from the SR?
Ryanodine Receptor (RyR1)
What ethnicity/nationality are susceptible to MH?
Native Americans
What are the symptoms of MH?
An acute increase in skeletal muscle metabolism
Increase O2 consumption
Lactate formation
Heat Production (why they get a fever later on)
Rhabdomyolysis (Spiked increase ETCO2, Increase temp 1C/5mins, arrhythmias, rigidity.)
What are the emergency ABCDs of malignant hyperthermia?
Dantrolene has decreased the mortality of MH from 80% to ________%.
10%
What is the dose of dantrolene?
2mg/kg IV
Repeat doses until symptoms subside or 10mg/kg IV
How does dantrolene work?
How is dantrolene metabolized?
- Inhibits the Ca2+ release from the SR and produces a muscle relaxant effect.
- Dantrolene is metabolized in the liver to 5-hydroxydantrolene that has muscle relaxant properties
Patients on calcium channel blockers (verapamil, Cardizem) that receive dantrolene as a treatment can result in __________
Cardiovascular Collapse (*d/t synergistic effects for Dantroline (a calcium channel blocker) added to other calcium channel blockers.
What are the most common side effects of dantrolene?
What are less common S/Es?
Most Common: Weakness, Phlebitis (vein inflammation), Respiratory Failure, GI upset
Less Common: Confusion, Dizziness, Drowsiness
What autoimmune disease develops Antibodies against the ACh receptor?
Symptoms (Sx)
Treatment (Sx)
Myasthenia Gravis (MG)
Sx:
Increasing weakness and fatigue throughout the day
Diplopia
Ptosis
Extremity and Resp muscle weakness
Tx: Cholinesterase Inhibitor
What part of the day would a Myasthenia Gravis patient be scheduled for surgery?
Should be the first for the day. When they have the most ACh and their ACh receptors are not worn out.
Myasthenia Gravis patients are _________ to Succinylcholine. Why?
What is the dose of SCh for MG patients?
Resistant to SCh. More SCh is needed because the ACh receptors that are left do not function as well.
1.5-2.0 mg/kg of Sch rather than the 1 mg/kg dose
*Their ED95 is 2.5x more
What is Lambert-Eton (LE) disease?
LE has an increased sensitivity to which type of NMBD?
Autoimmune disease: LE can produce antibodies against calcium channels and decrease the release of ACh pre-junctionally.
LE has a sensitivity to both depolarizing and nondepolarizing NMBD.
How would succs work in LE?
The succs would work sooner and with a lesser dose. The opposite of MG.
Why does Lambert-Eton disease often develop?
Often results from small-cell lung cancers.
