NMB & Succinylcholine (3) Flashcards
What is the modern form of curare that came about in 1940 that is not on the market anymore
dTc
When did succinylcholine come out?
1960
- dirty drug with lots of side effects
What is the primary purpose of Succs?
- provide NMB very quickly within second
- reason why its used for RSI
What is the down side of Pancuronium (Pavulon)?
- Last a long time
- Causes tachycardia
- not used often
Why did Rapacurium (Raplon) get taken off the market?
- Causes severe bronchospasms–especially in young men causing death
What is the MOA of neuromuscular blocking drugs?
Interrupt transmission of nerve impulses at neuromuscular junction (NMJ)
How do depolarizing NMB MOA differ from non-depolarizing NMB?
- Depolarizing NMB mimic that action of acetylcholine
- Non-depolarizing NMB interfere with the action of acetylcholine
What is the only drug we have that is a depolarizing NMB?
Succinylcholine (Anectine)
What is the purpose of using NMB?
- Minimizes the incidence of tissue trauma- decreased airway trauma
- Facilitated surgical exposure(easier for surgeon)
- Minimize patient injury from moving
What are NMB classifications based on?
- How long it lasts
- Chemical classification
What are the long acting non depolarizing NMBs and their classifications?
- Pancuronium (Pavulon): Aminosteroid
- Doxacurium: Aminosteroid
- Pipecuronium: Aminosteroid
What are the intermediate acting non-depolarizing NMB and the chemical classifications?
- Atracurium (Tracrium): Benzylisoquinoline
- Vecuronium (Norcuron): Aminosteroid
- Rocuronium (Zemuron): Aminosteroid
- Cisatracurium (Nimbex): benzylisoquinoline
What is the short acting non-depolarizing NMB and chemical classification?
Mivacurium (Mivacron): Benzylisoquinoline
What measures the potency/ correct dosing of NMBs?
ED95: Dose that produces 95% suppression of single twitch
What twitch occurs when stimulating adductor pollicis muscle?
Ulnar nerve is stimulated and the thumb moves (adduction)
When a NMB is given there is a ______ of onset and offset for muscles.
Order
What is the order of muscle paralysis of the block dependent on?
- Number of presynaptic Ach vesicles released
- Number of postsynaptic Ach functioning receptors
- Blood flow to the area
- Drug potency
What muscles block FASTEST?
Small, rapidly moving muscles block faster than large muscle
(eyelids, fingers, tongue fasciculation)
__________ would be expected to block faster than the diaphragm
Eyes
Central muscles paralyze ___________ than distal muscles
Faster
Which muscles would paralyze faster: Laryngeal muscle, ulnar nerve, foot
Laryngeal would paralyze faster: More central
Why do we not monitor adductor pollicis muscles for readiness to intubate post NMB?
The larygneal nerve paralyzes before the ulnar nerve so there is no point in monitoring it because it will be the last thing to paralyze
If wait for adductor pollicis to paralyze laryngeal muscle paralysis may already be reversed
What muscle would be better to monitor with nerve stimulator to assess laryngeal paralysis prior to intubation?
Central muscles that would correlate with laryngeal paralysis (orbicularis oculi)
What muscles do we monitor to know when the paralytic is reversing itself?
Extremities (adductor pollicis)
Gold standard for recovery from NMB
Laryngeal muscle reverses ___________ than peripheral muscles following NMB administration
Quicker
What is the problem with monitoring obicularis occuli for reversal of NMB?
More closely reflects diaphragm and layngeal muscles blockade BUT underestimates residual paralysis
Might have twitched back at orbicularis oculi, but not in adductor pollicis
Where are the positive and negative electrodes placed with a nerve stimulator?
- Positive (red): place proximal- 2-3cm away from negative electrode
- Negative (black): place distal- 1-2cm below skin crease on wrist
What is the single twitch on the nerve stimulator?
- Turn up to 10
- Usually 1 Hz/sec decreasing to 0.1 Hz every 10 seconds
- Continuous twitch until you turn it off
- Onset of block= fade with each stimulus
What is double burst on nerve stimulator?
- 2-3 short twitches followed by 2-3 short twitches (pause between)
- 50 Hz- supramaximal current
- Developed to improve detection of residual block
What mode on nerve stimulator is qualitatively better than TOF at detecting residual paralysis?
Double burst
- does the second one fade from the 1st one
What is the TOF mode on nerve stimulator?
- 4 stimuli at 2 Hz in 0.5 second
What is the TOF ratio?
Looking at how 4th twitch compares to the 1st twitch
What is a TOFR of 1?
Same strength of twitch on 4th twitch and 1st twitch
When during induction would we expect TOFR = 1?
Prior to NMB
What is the TOFR if 4th twitch is 1/2 of 1st?
TOFR= 0.5
- Very subjective
Its very difficult to detect fade if TOFR is > _____
0.4
If TOFR is 0.7-0.9 is there still blockade at NMJ?
Yes, there is still significant blockade at NMJ
* even if you think you have 4 twitches you still need to reverse because there is still a lot there
What is tetanic stimulation from nerve stimulator?
- Very rapid, 50Hz for 5 seconds
What type of response is seen from tetanic stimulation with non-depolarizing and depolarizing NMB?
Depolarizing: sustained muscle response (no fade)
Non-depolarizing: Non sustained response (fade)
What is the fade in tetanic stimulation with non-depolarizing NMB related to?
- Presynaptic depletion of AcH or inhibition of release
- Frequency and length of stimulation
What happens if multiple doses (more than 3) of succs are given close together?
Succs overdose (phase II): could causes non sustained tetanic response
What is post tetanic stimulation?
Single twitch 3 seconds after tetanic stimulation
What causes post tetanic stimulation?
Accumulation of calcium during tetany- excess calcium stimulates Ach release
What does it mean if there is no response to tetany or post tetanic stimulation?
Intense deep block
If there is a post tetanic twitch, what would come back next?
Tetany then TOF
Reverses itself in the order that is got stronger
How doe the nerve stimulator compare when testing tetany on a person with no block, depolarizing NMB, and non-depolarizing NMB?
depolarizing: equal decrease in strength
non-depolarizing: initial normal then decrease
How does TOF vary between no block, depolarizing and non depolarizing blocks?
How does the nerve stimulator compare when testing double burst on a person with no block, depolarizing NMB, and non-depolarizing NMB?
How doe the nerve stimulator compare when testing post-tetanic potentiation on a person with no block, depolarizing NMB, and non-depolarizing NMB?
What are some of the bedside criteria/tests for extubation? Why is extubation more successful when testing nerve impulses?
- Headlift
- Negative IP 25-30 cmH2O
- Use of nerve stimulator increases use of neostigmine and decreases post op blockade
What is the presynaptic cell for a skeletal muscle?
Motor neuron: large myelination from spinal cord or medulla
What part of the motor neuron innervates a single skeletal muscle fiber?
Motor nerve ending: unmyelinated
What are the responsibilities of the motor neuron?
Storing and secreting Ach (synthesis and release)
- reuptake of choline
How wide is the NMJ/synaptic cleft and what is it made up of?
- 20-50nm wide with fluid
- contain collagen, acetylcholinesterase
How many vesicles in the motor neuron release Ach and what is the release dependent on?
5,000-10,000 vesicles (ready pool)
- dependent on calcium
How does acetylcholinesterase break down Ach in the synaptic cleft?
- Hydrolysis of Ach → into acetic acid and choline
What is the shape of the post synaptic membrane (skeletal muscle)?
Membrane with multiple folds
What is the resting membrane potential of a skeletal muscle?
- -90mV→ maintained by sodium and potassium
nAch- receptors are a _________ unit
Pentameric→ 5 sub pores
Where are nAch-r located?
Transmembrane
What happens to nAch receptors when Ach binds?
Conformational change
- pores open, sodium/calcium/potassium flow
What happens to nAch-r if non depolarizing NMB binds?
- No conformational change
- No ion flow
- Binding probability r/t concentration of NMBD vs Ach
How many subunits does succs have to bind to on the nAch-r receptors?
- Only requires binding at 1 alpha subunite
- Can leave 1 receptor and attach to other nAChRs until hydrolyzed
What is thought to be a factor to the fasciculations associated with succs?
They occur has succs hops from receptor to receptor (on/off response that causes fasciculations)
What are 2 unique characteristics of succs?
- Intense, rapid paralysis
- Offset of effects prior to hypoxia
When is it useful to use succinylcholine?
Trachea intubation when concern for airway protection (RSI)
Does succinylcholine release histamine?
Yes
What is the dose, onset, and duration of succinylcholine?
1 mg/kg actual body weight
onset: 30-60 seconds
duration: 3-5 min
What is the MOA of succinylcholine?
Attaches to 1 or both alpha subunits: Fasciculations from hoping from one alpha subunit to another
mimics effects of ACh
How does the breakdown of Succs compares to ACh?
Hydrolysis of succs is slower than ACh
- sustained opening of receptor ion channels
- leakage of K+ ions= 0.5mEq/L increase
What phase block is depolarization of non depolarizing?
Depolarizing= phase I
Non depolarizing= phase II
What are characteristics of phase I blocks?
- decrease contraction to single twitch stimulation
- decrease amplitude to continuous stimulation
- TOF ratio >0.7
- absence of post tetanic facilitation
- skeletal muscle fasciculations
What phase would be prolonged paralysis of succs/ too much succs?
Phase II–from desensitization
When can succs go into a phase II block?
- 2-4 mg/kg (not the best to re-dose succs)
- lack of pseudocholinesterase
- abrupt transition from phase I to phase II
What happens if someone has abnormal pseudocholinesterase activity and you gave them succs?
They will go to recovery on vent until the block wears off (not breaking down succs as fast d/t lack of enzyme)
What in a factor that increases metabolism of succs by increasing plasmacholinesterases?
Obesity (why we use actual body weight)
What can prolong succinylcholine NMB by decreasing peusdocholinesterase activity?
- decrease hepatic production
- drug induced decrease
- genetically atypical
- chronic disease (renal)
- pregnancy (high estrogen levels)
Which plasma cholinesterase hydrolyzes succs?
Butyrylcholinesterase
Where is butyrylcholinesterase synthesized?
Liver
Where do NDMB bind?
Have to bind to both receptors on nAChRs
What does succs become when its metabolized by butyrylcholinesterase?
Succinylmonocholine and choline
What drugs can decrease activity of pseudocholinesterases?
- Neostigmine
- Reglan
- Chemo
- Insecticides
What is the dibucaine test for?
genetic pseudocholinesterase activity
What is Dibucaine and what is its action?
Amide local anesthetic
- Inhibits activity of normal variant butyrylcholinesterase (pseudocholinesterase)
What does the Dibucaine number represent?
How inhibited (% inhibition) the breakdown is→ lower number means succs response is more prolonged
- reflects quality of enzyme not quantity
What is a normal dibucaine number?
80
Which patients would you want to know the dibucaine number for?
- Tracheal stenosis (lasering airways)
- ECTs
frequently getting succs
What are side effects of succinylcholine?
- Cardiac dysrhythmias
- Hyperkalemia
- Myalgia
- Myoglobinuria
- intragastric pressure
- intraocular pressure
- intracranial pressure
- masseter spasm
What is pretreatment for succs?
- giving small dose of NDMB before giving succs
- blocks alpha subunits enough that we dont see fasciculations from succs
- no fasciculations= no increase in IOP/ICP
- weaken pt enough so they may feel chest heaviness/blurry vision (make sure to warn them)
What are cardiac dysrhythmias associated with succs and why do these occur?
Actions as cardiac muscarinic cholinergic receptors
- sinus brady
- junctional
- sinus arrest
Actions as ANS ganglia
- increase HR and BP
- mimic actions of Ach
- usually occurs with large doses
shouldnt notice too much of a difference in HR because the AND offsets the muscarinic actions
When are cardiac dysrhythmias most likely to occur with succs?
- Most likely on 2nd dose, 5 minutes after 1st dose
- due to metabolites succinylmonocholine and choline
Who are we worried about giving succs to and causing hyperkalemia?
- Patients with extrajunctional sites (more ion channels)
- muscular dystrophy
- unhealed 3rd degree burns
- denervation of skeletal muscles (Atrophy)
- skeletal muscle trauma
- upper motor neuron lesions
How can myalgia S/E of succs be mitigated?
Pretreat with advil or take after
What causes myoglobinuria from succs?
- damage to skeletal muscles (esp in peds)
- usually found later to have MH or muscular dystrophy
Need to tell pt these findings and document
sometimes hard to know because alot of these pts arent getting foleys
What causes intragastric and lower esophageal sphincter pressure to increase when succs is given?
Inconsistent increases releated to
- intensity of fasciculations
- direct increase in vagal tone
When is the maximum increase in IOP following admin of succs and how long does it last?
- 2-4 minutes after giving succs (halfway through MOA)
- lasts 5-10 minutes
What is the MOA of increased IOP with succs?
unknown
When is succs absolutely contraindicated in relation to eye issues?
open globe injury
How can increased intracranial pressure with succs admin be attenuated?
Hyperventilation prior to succs
- increase ICP in pts with intracranial tumors or closed head injuries
What is a common sustained skeletal muscle contraction with succs?
- jaw/ masseter muscle spasm
- differential dx with MH, opioids, inadequate dose of succs
What is malignant hyperthermia definition?
Hereditary rhabdmo associated with anesthetics
- Muscle destruction
- Hyperkalemia
- Acidosis
- Dysrhythmia
- Renal failure
- DIC
What are triggers for MH?
- volatiles
- succs
What causes malignant hyperthermia?
- mutations in skeletal muscle calcium release
- RyR 1 (50-70% MH patients)
What is the gold standard for dx malignant hyperthermia?
- Skeletal muscle caffeine contracture testing (muscle biopsy)
What are symptoms of malignant hyperthermia?
- Acute increased skeletal muscle metabolism
- Increased oxygen consumption
- Lactate formation
- Heat production
- Rhabdomyolysis
- ↑ ETCO2—cant bag to decrease (continues to increase)
- ↑ temp 1 degree C/5 minutes
- Arrhythmias
- Skeletal muscle rigidity
What is the treatment for MH? (ABCD)
A:
- agents: stop triggering agents
- administer non triggering anesthetics
- ask for help
- ask for MH cart
B:
- Breathing: hyperventilate with 100% O2
C:
- cooling procedures if pt >102.2
D:
- Dantrolene: continuous rapid IV push
What is the dose of dantrolene?
2mg/kg: repeat dose until symptoms subside or max 10mg/kg IV
What is the MOA of dantrolene?
CCB: inhibits calcium release into SR
Where is dantrolene metabolized and what effects might it cause?
- metabolized in the liver into 5-hydroxydantrolene
- muscle relaxant properties
- 50% pt have weakness (decrease grip strength)
- CV collapse (may need CO support from excess CCB)
What are side effects of dantrolene?
Common:
- weakness
- phlebitis
- resp fx
- gi upset
Less common:
- confusion
- dizziness
- drowsiness
What would you expect as far as dose for succs when using in a patient with myasthenia gravis?
Fewer receptors–resistant to succs
would need to increase the dose for these pts (1.5-2.0 mg/kg) lasts longer
ED95 2.5x higher
What is MG MOA and S/E?
Autoimmune disease
- Antibodies against Ach receptor
- ↓ Ach receptors
- Resistance bc not enough receptors to block the muscles –would need to give more succs and it will last longer
Increasing weakness/fatigue
- Diplopia
- Ptosis
- Extremity and respiratory muscle weakness
- Tx with cholinesterase inhibitors
What is lambert-eton disease?
Autoimmune disease
- Small-cell lung cancer
- Antibodies against calcium channels
- Decreases release of Ach pre-junctionally
What would be expected for the succs dose in a pt with lambert eton disease?
Increased sensitivity in depolarizing and NDMB: blocks earlier with less
