NMBDs: Physiology/Succinylcholine (Exam III) Flashcards
Which of the following is the newest NMBD?
A. Atracurium
B. Vecuronium
C. Pancuronium
D. Cistracurium
E. Succinylcholine
A. Atracurium (1980)
B. Vecuronium (1980)
C. Pancuronium (1960)
D. Cistracurium (1995)
* E. Succinylcholine (1940-1960)
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 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
What classification of NMBD is Succinylcholine (Anectine)?
Depolarizing NMBD
Only depolarizing agent used in anesthesia.
Name a long-acting non-depolarizing NMBD.
Pancuronium (Pavulon)
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)
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
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.
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.
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?
Is the red electrode positive or negative?
Do you place it proximal or distal?
- Red = positive electrode
- Proximal placement
Is the black electrode positive or negative?
Do you place it proximal or distal?
- Black = negative
- Distal
What are 3 locations on the body to test nerve stimulation?
- Adductor pollicis (ulnar nerve)
- Obicularis Occuli (facial nerve)
- Flexor Hallucis Brevis (posterior tibial nerve)
What is a defasciculating dose of NMBD?
What symptoms will the patient experience with a defasciculating dose?
Where 20% of intubating dose is given early (primer) to prevent fasciculation.
Blurred Vision
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 week and get blurry vision. Encourage them to close their eyes.
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
- This is a continuous single twitch, back to back, to back
Double burst stimulator is _____ short bursts followed by ______ short bursts.
The double burst stimulator setting uses ________ Hz
3, 3
50 Hz (supramaximal current) Stronger current than single twitch.
Why was the double burst stimulator developed?
- Developed to improve detection of residual block (fade). Detects residual paralysis.
- 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
- Train of 4 ratio is very subjective/qualitative
TOF reflects events at _________ membrane.
Presynaptic
Prior to NMBD what will be your twitches on the TOF?
What will be the TOF ratio (Twitch 4 : Twitch 1)?
4/4 twitches
Ratio 1
What is the TO4 ratio if the amplitude of the 4th twitch is only 50% of the 1st twitch?
TOFR = 0.5 or 50%
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)
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?
Besides a TOF, what are 2 other bedside criteria for extubation?
- Patient can lift their head
- A negative PIP of 25-30cmH2O
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%
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%
The presynaptic motor neuron is large and _________ which helps with transmission of nerve impulses.
Where does the presynaptic motor neuron come from?
myelinated
Spinal cord or medulla
The motor nerve ending is ________ and innervates single muscle fibers.
unmyelinated
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
How many vesicles release ACh at the synaptic cleft?
5,000-10,000
What does Acetylcholinesterase do to ACh?
Hydrolyze ACh to acetic acid and choline
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+
When acetylcholine binds to the nACh receptor, what ions flow across the membrane?
- Sodium
- Calcium
- Postassium
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 ______.
- conformational change
- No ion flow through the channel
Succinylcholine only requires binding at one ________ subunit. It is postulated that this will cause ________ before total blockade.
- one alpha subunit
- fasciculation
- Can leave 1 receptor and attach to anoher nACh receptor until its hydrolyzed. This is what causes he muscle fasiculations.
_________ 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
- Offset 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 (use actual body weight not ideal 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).
- Sustained opening causes leakage of K+ ions at 0.5mEq/liter serum increase.
- Depolarization is called a phase 1 block
SCh will cause how much increase in serum K+?
0.5 mEq/L
What are characteristics of a phase I block when giving SUX?
- 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.
What can antagonize phase 2 blocks?
non-depolarizing
Anticholinesterase drugs
How can a Phase I block transition to a Phase II block?
- Essentially an overdose
- Large dose of SCh (2-4 mg/kg)
- Lack of/ poorly functioning pseudocholinesterase
Succinylcholine is hydrolyzed by __________.
Butyrylcholinesterase (plasma cholinesterase)
Where is Succinylcholine metabolized?
Where is it terminated?
What is its metabolite?
- Metabolized in the liver
- Terminated by diffusion out of the NMJ into plasma.
- Metabolite = Succinylmonocholine (less potent) and choline
What factors can decrease pseudocholinesterase activity?
What does this mean clinically?
- Hepatic disease
- Drugs (neostigmine, reglan, chemo, insecticides)
- Genetics
- CKD
- Estrogen (think pregnancy)
- The duration of action is prolonged. EX: 10 minutes instead of 3-5 minutes
What factor can increase pseudocholinesterase activity?
What does this mean clinically?
- Obesity
- Higher dosing of succinylcholine is necessary for obese patients.
- The duration of action is much shorter/ quicker. EX: 1 minute instead of 3-5 minutes.
What is Dibucaine?
- An amide local anesthetic that inhibits the activity of Butyrylcholinesterase (pseudocholinesterase)
What does dibucaine number mean?
What does it mean in extremely simple terms?
- % inhibition = Dibucaine number
- Dibucaine number reflects the quality (not quantity) of the enzyme that inhibits the breakdown of butyrylcholinesterase. (pseudocholinesterase)
- ↑ 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
Less butyrylcholinesterase will stick around
What are the side effects of Succinylcholine?
- Cardiac dysrhythmias (SB, JR, sinus arrest, increased HR and BP usually ocurrs with large doses)
- Hyperkalemia
- Myalgia (due to muscle fasiculations, often confused with pharyngitis due to intubation)
- Myoglobinuria (due to damage to skeletal muscles especially in pediatrics, usually found later to have malignant hyperthermia or muscular dystrophy)
- ↑ Gastric pressure, and lower esophageal pressure (makes patient more likely to aspirate because it is pushing gastric content up towards lower airway)
- ↑ IOP (increases IOP around 2-4 minutes after administration, lasts 5-10 minutes, SUX contraindicated in open globe injury)
- ↑ ICP (in patients with intracranial tumors and closed head injuries, the increase in ICP can be overcome by hyperventilation prior to SUX to decrease CO2 and CBF)
- Masseter spasm (due to sustained skeletal muscle contraction, is an early indicator of MH, can be an indicator of inadequate dose given in children)
What is the pre-treatment to the side effects of SCh?
- Pre-treatment with non-depolarizing NMBD (5mg of Roc).
This defasciculating dose either decreases, prevents, or mask the side effects of SCh.
What dysrhythmias can occur with succinylcholine administration?
- ↓HR
- 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.
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?
What is myalgia often confused with post extubation?
Young adults
Neck, back, abdomen
Often confused with pharyngitis due to intubation.
Pediatric patients more frequently experience this with succinylcholine administration.
Myoglobinuria (from damage to skeletal muscles), usually found later to have MH or muscular dystrophy.
No succinylcholine for children
Sch will increase intragastric pressure and LES pressure, this will increase risk of _______.
What patient population is this not seen in and why?
Aspiration
This is related to the intensity of the fasciculation and the direct increase in vagal tone.
- Not seen in children due to minimal fasiculations.
Sch will increase intraocular pressure _______ minutes (range) after administration and last _________ minutes (range).
2-4 minutes after admin
last 5-10 minutes
Sch will be contraindicated 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.
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)
What is the definitive testing for MH?
- skeletal muscle caffeine contracture testing using a muscle biopsy
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). Happens in 50-70% of MH patients
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
- Rhabdomyolysis (Spiked increase ETCO2, Increase temp 1C/5mins, arrhythmias, skeletal muscle 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?
- Is a calcium channel blocker
– Inhibits the Ca2+ release from the SR and produces a muscle relaxant effect. - Dantrolene is metabolized in the liver to 5-hydroxydantrolene
Patients on calcium channel blockers (verapamil, Cardizem) that receive dantrolene as a treatment can result in __________
Cardiovascular Collapse (d/t synergistic effects)
What are the most common side effects of dantrolene?
What are less common S/Es?
Most Common: Weakness, Phlebitis, 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 of 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
2.These patients need a bigger dose and it takes longer to wear off
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 an increased sensitivity to both depolarizing and nondepolarizing NMBD.
- Will block earlier than it normally would with a little bit less of a dose.
Why does Lambert-Eton disease often develop?
Often results from small-cell lung cancers.
