06 - NMB Agents and Reversal Flashcards
1
Q
what is the neuromuscular junction?
A
the narrow gap between neuron and muscle fiber
2
Q
when the nerve depolarizes, which ions and neurotransmitters are involved?
A
Ca ions enter neuron and ACh is released from vesicles
3
Q
where does ACh bind?
A
ACh binds nicotinic cholinergic receptors on motor end-place of muscle fiber
4
Q
how does ACh work?
A
ACh receptor opens ion channel to generate end-plate potential
potential propogates along muscle membrane leading to contraction
amt of ACh released far exceeds (by 10-fold) amount needed for depolarization
5
Q
how is ACh hydrolyzed? what are the products?
A
ACh is hydrolyzed into acetate and choline by acetylcholinesterase (AChE)
embedded in motor end-plate membrane
6
Q
what happens to the muscle when ACh receptors close and end-plate repolarizes?
A
muscle begins to relax
7
Q
describe NMB agents and reversal
A
quaternary ammounium compounds with affinity for nicotinic ACh receptors
8
Q
what happens with depolarizing NMBs?
A
cloely resemble ACh and bind to ACh receptors (agonist)
generate muscle action potential
9
Q
T/F depolarizing NMBs are metabolized by AChE
A
False
10
Q
what is a Phase I block?
A
end plate cannot repolarize, muscle becomes flaccid.
peripheral nerve stimulation: constant but diminished twitch, no fade, no post-tetanic potentiation
11
Q
what is a Phase II block?
A
prolonged depolarization causes abnormal response to ACh
resembles non-depolarizing block
12
Q
what happens with non-depolarizing NMBs?
A
bind ACh receptor but cannot induce ion channel opening (competitive agonist)
13
Q
where do non-depolarizing NMBs bind?
A
bind to a subunit of ACh receptor so ACh cannot bind, but receptor is not activated
14
Q
T/F non depolarizing NMBs do not generate end-plate potential
A
true
15
Q
what percentage of receptors are blocked before fade is observed?
A
> 70%
16
Q
what percentage of receptors are blocked before complete twitch suppression is observed?
A
> 90%
17
Q
what is peripheral nerve stimulation?
A
fade effect during prolonged/repeated stimulation
18
Q
why would there be fade of twitches?
A
less ACh available in nerve terminal
19
Q
when is fade most obvious?
A
sustained tetanus or double-burst stimulation
20
Q
how are depolarizing agents reversed?
A
diffuse away from NMJ -> hydrolysis by plasma pseudocholinesterase
Phase I block: no reversal agent exists
21
Q
what happens if you try to reverse a depolarizing agent with AChE inhibitor?
A
reversal of Phase I block with AChE inihbitor can lead to prolonged depolarization
reversal of Phase II block with AChE inhibitor may be appropriate
22
Q
how are non-depolarizing agents eliminated?
A
redistribution, metabolism, excretion
23
Q
how will the amount of ACh be affected if you inhibit AChE?
A
increase amount of ACh in NMJ
increased AChe will compete with the NMB drug
24
Q
what is the only available depolarizing muscle relaxant?
A
succinylcholine
25
what is the structure of succinylcholine?
two joined ACh molecules
26
what is the onset of sux? duration?
rapid onset - 30-60sec
| short duration - <10min
27
what is sux metabolized by?
pseudocholinesterase (only a small fraction actually reaches NMJ)
28
what factors would cause prolonged action of sux?
hypothermia
pregnancy
liver disease
renal failure
29
how long will sux last with a 1:50 heterozygous abnormal pseudocholinesterase gene?
20-30min block
30
how long will sux last with a 1:3000 homozygous abnormal pseudocholinesterase gene? how do you treat it?
4-8 hour block
| treat with mechanical ventilation
31
how does dibucaine affect sux?
dibucaine is a LA that inhibits pseudocholinesterase
32
what is the dibucaine number? normal values?
% inhibition = dibucaine number
normal = 80
heterozygous = 40-60
homozygous = 0-20
33
what do cholinesterase inhbitors do? how?
prolong phase 1 depolarizing block
inhibition of AChE -> high conc of ACh -> intensify depolarization
inhibition of pseudocholinesterase -> reduced hydrolysis of sux
34
what's an example of a cholinesterase inhibitor?
organophosphate pesticides
35
which nondepolarizing NMBA inhibits pseudocholinesterase?
pancuronium
36
what can small doses of nondepolarizing NMBA do to sux?
small doses can antagonize depolarizing block
37
what is the IV dose of sux?
1-1.5 mg/kg
| as low as 0.5 mg/kg if defasiculating dose not used
38
will higher or lower doses of sux increase likelihood that spontaneous breathing will resume after desaturation?
lower
39
do you use true body weight or ideal body weight to calculate dose of sux?
true body weight
40
T/F boluses (10mg) can be repeated
true
41
how would you run an infusion of sux?
0.5-10mg/min (mix 1-2 vials in 100mL bag)
titrate to effect
use nerve stimulator to prevent Phase II block
42
what is the IM dose of sux?
4-5 mg/kg
43
what is the dose of sux for layngospasm?
0.1 mg/kg IV
44
T/F the side effects of sux are related to its resemblance to ACh
true
45
what are the CV side effects of sux?
binds muscarinic cardiac ACh receptors:
bradycardia, decr contractility
opposite effect at highser doses (binds nicotinic ACh receptors in autonomic ganglia ?)
46
when is bradycardia especially seen with sux?
children and 2nd dose in adults
| consider prophylactic treatment with atropine
47
how can fasiculations be prevented?
small dose of non depolarizing durg, 5 min in advance
48
how is hyperkalemia caused with sux?
sustained opening of ion channels and membrane depolarization
49
how much is serum K+ increased with sux?
0.5 mEq/L
50
when will there be a significant K+ release? why?
trauma, denervation
rapid proliferation of extrajunction ACh receptors with neural injury
widespread depolarization -> significant K+ release
51
T/F pre-tretament with nondepolarizer will prevent hyperkalemia
FALSE
pre-treatment with nondepolarizer will NOT prevent hyperkalemia
52
when can higher instances of hyperkalemia be seen?
```
3rd degree burn injury
massive skeletal trauma
upper motor neuron injury
denervation -> muscle atrophy
myopathies (myotonia, muscular dystrophy)
```
potential risk within 96 hrs
peaks 7-10 days after injury
lasts 6 mos or longer
53
how can myalgia with sux be prevented?
defasiculating dose of nondepolarizer
54
how is ICP and gastric pressure affected by sux?
increased ICP and gastric pressure
not consistently observed
both can be attenuated with defasiculating dose
55
how is IOP (intraocular pressure) affected by sux/
increased
no reports of extrusion of ocular contents with succinylcholine
IOP not attenuated with defasiculating dose
56
when will a phase II block occur with sux?
after 2-4 mg/kg IV or after a single dose, in pts with atypical plasma cholinesterase
57
how does a phase II block occur?
presynaptic block reducing the synthesis and mobilization of ACh, and postjunctional receptor desensitization
58
do inhalation anesthetic drugs accelerate or decelerate onset of Phase II block?
accelerate
59
how can you antagonize a Phase II block?
anticholinesterase drugs but response is difficult to predict
60
how do you treat a Phase II block?
advisable to allow spontaneous recovery
61
T/F sux is a potent trigger for malignant trigger
malignant hyperthermia
62
what can look like MH?
young pt with undiagnosed muscular dystrophy going into hyperkalemic cardiac arrest
neuroleptic malignant syndrome (NMS)
masseter muscle rigidity (MMR)
63
symptoms of neuroleptic malignant syndrome (NMS)?
hyperthermia, muscular hypertonicity, autonomic instability, mental status changes
related to administration of antipsychotic drugs
64
what is masseter muscle rigidity?
trismus making it difficult/impossible to open jaw
mild/transient MMR in response to sux is normal
65
when is MMR seen?
1-4% of children receiving halothane/sevo and sux
when MMR occurs following sux, elective surgery can be postponed
66
how do you treat MMR? NMS?
MMR - assume it is MH and begin treatment
pt should remain in hospital for 24 hrs. monitor signs of rhabdomyolysis (myoglobinuria and myoglobinemia). check CK levels and electrolytes q8h
NMS - no MH precautions necessary
67
what can sux-induced MMR lead to?
rhabdomyolysis
68
to summarize...
| ABSOLUTE contraindications of sux are?
```
MH
dangerously high serum K+
known myotonia or muscular dystrophy
>2-4 days after CNS injury (stroke, cord injury)
massive musculoskeletal injury
major burn
```
69
what are the two types of non-depolarizing neuromuscular blocking agents?
benzoisoquinolines ("-acurium")
| steroidals ("-curonium")
70
what are the onset and duration times of nondepolarizing NMBs?
slower than sux
| speed onset with higher dosing than usual - can lead to prolonged recovery times
71
what is the priming dose of nondepolarizing NMBs?
10% of intubating dose 5 min before induction
anxiety, dyspnea, dysphagia, desaturation in some pts
72
what is the defasiculating dose of nondepol NMBs?
10% of intubating dose 5 min before sux
| may need higher doses of sux (up to 1.5 mg/kg)
73
how do you maintain nondepol NMBs?
intermittent boluses or continuous infusion
74
what can potentiate nondepol NMBs?
inhalational agents (des>sevo>iso>hal)
ABX (aminoglycosides - prolong steroidal NMBs)
phenytoin
Mg
75
prolonged action of nondepol NMBs?
hypothermia
acidosis
hypokalemia
hypocalcemia
76
which muscles are more sensitive to NMB?
muscles of glottis, face, airway, and diaphragm are LESS sensitive to NMB than the thumb (adductor pollicis)
dose to block diaphragm is twice the dose needed to block adductor pollicis
77
how is cisatacurium metabolized?
Hoffman elimination
| does not rely on pseudocholinesterase, renal, or hepatic elimination
78
which is a common drug in renal failure and for ICU infusions?
cisatracurium
79
what is the dose of cis?
0.1-0.15 mg/kg
80
what is the onset and duration of cis?
onset - 2-4 min
| duration - 35-40 min
81
how do you store cis?
keep it refrigerated
82
what is atracurium?
isomer of cisatracurium
hypotension and histamine release at higher doses
83
how is atracurium degraded?
Hoffman elimination AND ester hydrolysis by non-specific plasma esterases
degraded into laudanosine (seizures) and acrylate fragments
84
what NMB has fast onset, is short-acting, metabolized by pseudocholinesterase, and is no longer available?
mivacurium
85
which NMB is a long-acting agent an can be more difficult to reverse than other agents?
pancuronium
86
what percentage is pancuronium renally cleared?
40%
| caution in renal failure!!
87
how does pancuronium affect HR, BP, CO
increases in HR, BP, CO (block cardiac muscarinic ACh receptors)
88
what is the dose of pancuronium? onset and duration?
dose - 0.08-0.12 mg/kg
onset - 2-4 min
duration - 60-120 min
89
how do you redose pancuronium?
~0.01 mg/kg every 20-40 min
90
what percentage is vecuronium renally cleared?
25%
91
dose of vec? onset and duration? redose?
dose - 0.08-0.12 mg/kg
onset - 3-4 min
duration - 35-45 min
redose every 15-20 min
92
dose of roc? onset and duration? redose?
dose - 0.45-0.9 mg/kg
onset - 2 min (90 sec with 1.2mg/kg)
duration - 30-40 min
redose 0.15 mg/kg every 15-20 min
93
which NMBs are intermediate agents?
cis, vec, and roc
94
what are cholinesterease (AChE) inhibitors or "anticholinesterases"?
reversal agents
95
what are common AChE inhibitors?
neostigmine, pyridostigmine, edrophonium, physostigmine
96
how do AChE inhibitors work?
indirectly increase amount of ACh in the NMJ which can compete with the nondepolarizing NMB agent
reversibly bind to the AChE enzyme
may be other mechs as well (presynaptic actions and non-ACh-mediated actions)
97
T/F organophosphates (pesticides) are also anticholinesterases
true
98
what disease are reversal agents used in diagnosis and treatment of?
myasthenia gravis
99
what happens with excessive doses of AChE inhibitors?
can cause ACh-mediated blockade which can lead to weakness
recommend decreased dose if recovery from NMB is almost complete
100
what will pseudocholinesterase inhibition do to sux?
some degree of it can prolong action of sux
101
what are side effects of reversals? why?
```
CV - bradycardia
pulm - bronchospasm, secrertions
CNS - excitation (only physostigmine crosses the B-B barrier), miosis (pupillary constriction)
GI - N/V, GI activity, salivation
SLUDGE BB
```
due to increased systemic ACh
102
how do you treat the side effectes of AChE inhibitors?
anticholinergic agent like glycopyrrolate
glyco does cross B-B barrier, atropine does
103
clearance of AChE inhibitors?
hepatic - 25-50%
| renal - 50-75%
104
what must you have before giving reversal drug?
evidence of spontaneous recovery
TOF with fade - full reversal dose
TOF without fade - partial reversal dose
sustained 5sec tetanus or cliinical evidence of adequate strength - consider no reversal (!!)
no tetanic response - unreversible
105
what do you consider when evaluating spontaneous recovery?
sustained head lift/leg lift > neg inspiratory force > vital capacity > tidal volume
106
speed of different reversals?
edrophonium > neostigmine
higher dose speeds reversal
shorter-acting agents reverse faster than long-acting agents
severe end-organ dz can prolong block (renal/hepatic failure)
107
dose of neostigmine? onset, peak, duration?
0.04-0.08 mg/kg (up to 5 mg in adults)
give 0.2 mg of glyco with every mg of neo
onset - 5 min
peak - 10 min
duration - 1 hr
108
when would you consider atropine instead of glyco?
neo may cross the placenta
109
T/F pyridostigmine has longer onset/duration
T
110
what is the onset and duration of edrophonium?
rapid onset of action (1-2 min)
short duration of effect
give with atropine - better match with onset, duration
111
what is the structure of physostigmine?
tertiary amine
| crosses B-B barrier
112
what is physostigmine used for?
treatment for central cholinergic toxicity
reverses some CNS depression/delirium associated with volatile anesthetics and benzos
113
dose of physostigmine? how do you give it?
dose 0.04 mg/kg for post op shivering
| no need to co-treat with atropine/glyco, but have it ready
114
how is physostigmine metabolized?
plasma esterases
115
what is sugammadex?
reversal that selectively binds to roc, vec, and pancuronium
cyclodextrin ring binds tightly (but not irreversibly)
116
does sugammadex bind to benzylisoquinolines?
no. needs the steroid nucleus
117
when do you give sugammadex?
anytime. can reverse deep NMB
| could be used with roc for RSI and replace sux
118
what is myasthenia gravis?
neuromusc dz - antibodies to ACh receptors
119
can you give sux to myasthenia gravis pts?
resistant to sux
| may be due to pyridostigmine -> reduced pseudocholinesterase activity
120
how do myasthenia gravis pts react to nondepolaizers?
reversal may be incomplete - due to pyridostigmine therapy
| altose tries to avoid all NMB agents when possible, but not always feasible
121
what is myotonia?
abnormal delay in muscle relaxation after contraction
122
how do myotonia pts respond to sux?
sustained contracture, hyperkalemia
123
how do myotonia pts respond to nondepolarizres?
normal response
| avoid reversal agents -> myotonic responses
124
what is muscular dystrophy?
loss of muscle mass
125
how do muscular dystrophy pts respond to sux?
hyperkalemic cardiac arrest
pts <10y old (esp males) may have latent, yet-undiagnosed dz
126
how do muscular dystrophy pts respond to nondepolarizers?
normal resposne
127
what are some upper motor neuron lesions?
hemiplegia, quadriplegia
128
how do hemiplegia/quadriplegia pts respond to sux?
hyperkalemia
| starts ~2-4 days after injury -> 6-12 mos
129
how do hemiplegia/quadriplegia pts respond to nondepolarizers?
resistance to nondepolarizers below the level of lesion
130
what do burns lead to?
proliferation of extra-junctional receptors
131
how do burn pts respond to sux?
hyperkalemia starting ~2-4 days after the burn -> at least 12 months
132
how do burn pts respond to nondepolarizers?
resistance to nondepolarizing agents
