Neuromuscular Blocking Drugs Flashcards
What a patient can do when 50% of their neuromuscular receptors are still occupied
- Head lift
- Sustained bite
- Hand grip
- Inspiratory force >40cmH2O
- Sustained tetanus at 100Hz without fade
What a patient can do when still 60-70% of their neuromuscular receptors are occupied
- Sustained tetanus at 50Hz for 5 seconds without fade
- Vital capacity at least 20mL/kg
- Double-burst stimulation without fade
What TOF will do when 70-75% receptors are occupied
No palpable fade
What patient can do when 80% of receptors are still occupied
Tidal volume of at least 5mL/kg
Train of four
Series of four twitches at 2Hz given every half second
- Reflects blockade from 70-100%
- Train of four ratio determined by comparing T1 to T4
Double-burst stimulation
Two short bursts of 50Hz tetanus separated by 0.75 second
-May be easier to detect fade than To4
Tetanus
Rapid delivery of 30 50 or 100Hz for 5 seconds
- Use sparingly for deep block assessment, painful
- Have to hold button down for 5 seconds manually, safety feature
Posttetanic count (PTC)
50Hz tetanus for 5 seconds, then 3 second pause, then single twitches at 1Hz up to 20x
-Used when To4 or double burst stimulation is absent
-At 7-9 posttetanic twitches you should get a To4 1/4
-Used to dose sugammadex for deep blocks
Tetanus stimulates acetylcholine to come out (even though you won’t get a response to the tetanus, the AcH is then mobilized in the neuromuscular junction to temporarily complete with the NMBD in the junction
Clinical duration vs total duration of action of NMBDs
Clinical duration: Time from drug administration to 25% recovery of twitch response (still 75% paralyzed)
Total duration of action: Time from drug administration to 90% recovery of twitch response
When is recovery indicated per To4
When the fourth twitch is 90% of the first
Chemical structure of succinylcholine, mechanism of action
2 Acetylcholine molecules attached to each other
- Depolarize the nerve, stimulating muscle contraction just like acetylcholine
- But stays on the receptor much longer than acetylcholine, during which it cannot repolarize and is refractory to another contraction
Function of cholinesterase, 2 types
Terminate the action of acetylcholine at cholinergic nerve endings in synapses or in effector organs
Type 1: Acetylcholinesterase (in nerve endings)
Type 2: Pseudocholinesterase (in plasma, >11 enzyme variants)
Dibucaine inhibition test
Dibucaine=LA that inhibits typical pseudocholinesterase but not atypical
- Normal=80 (80% PchE activity inhibited)
- Result of 20 means patient has atypical enzyme (dibucaine didn’t inhibit the patients enzyme activity)
If prolonged apnea, what do these results indicate:
- Low dibucaine number, normal activity
- Normal dibucaine number, low activity
- Low dibucaine number, low activity
- Normal dibucaine number, normal activity
- Low dibucaine number, normal acitivity=atypical enzyme
- Normal dibucaine number, low activity=normal enzyme with low levels present
- Low dibucaine number, low activity=atypical enzyme with low levels present
- Normal dibucaine number, normal activity=normal enzyme and amount (different reason for apnea)
Hyperkalemia and succinylcholine (normal increase, pt population which will increase more)
Normally K increases by 0.5mEq/L (K leaks from depolarized muscles)
- May rise higher in patients after crush injuries, burns, denervating injuries, or malignant hyperthermia
- Also patients with disuse atrophy (quad or paraplegic, bedridden patient) or severe sepsis
Dysrhythmias and succinylcholine
Wide ECG complexes leading to cardiac arrest have been seen in children with muscular dystrophy
- Contraindicated in peds until their teenage years (may have muscular dystrophy and haven’t been diagnosed yet)
- Still used in peds laryngospasm
Malignant hyperthermia and succinylcholine
Succinylcholine triggers MH, not understood why
Masseter spasm and succinylcholine
Rare, seen more in children than adults
-Sometimes followed by MH
Succinylcholine use in burn patients
Acetylcholine receptors are greatly upregulated post burn for >1 year+, K can rise much higher than 0.5 in these patients, succinylcholine is contraindicated
2 chemical structures of non-depolarizing muscle relaxants
Benzylisoquinolines
-Cisatracurium (same as > but doesn’t cause histamine release), atracurium, mivacurium
Steroidal
-Rocuronium, vecuronium, pancuronium
Hoffman elimination
Requires a change in temperature and pH to start metabolism
- Drug in vial=room temp, pH 5.5 -> body=36C, pH 7.4
- Metabolizes the same in everyone, predictable
Succinylcholine metabolism
Plasma cholinesterase
Cisatracurium metabolism, elimination, and metabolite
Metabolism: Hoffman elimination and non-specific ester hydrolysis
Elimination: Renal clearance 16% total elimination
Metabolite: Laudanosine, can be CNS toxic but because cis is so potent the quantity of metabolite produced isn’t an issue
Vecuronium metabolism, elimination, metabolite
Metabolism: Liver 30-40%
Elimination: Kidney 20-40%, Liver 60-80%
Metabolite: 3-OH, accumulates in renal failure, may be responsible for delayed recovery in ICU patients
Rocuronium metabolism, elimination, metabolite
Metabolism: <1%
Elimination: Kidney 10-25%, Liver 70%
Metabolite: None
Which NMBDs may be prolonged with renal disease
Pancuronium, rocuronium
Which NMBDs may be prolonged with hepatic disease
Rocuronium, vecuronium
Which NMBDs will be prolonged with cholinesterase deficiency
Succinylcholine, mivacurium
Which NMBDs will cause histamine release
Atracurium and mivacurium, slight release may occur with succinylcholine
Cardiac effects of NMBDs (which cause hypotension/tachycardia, vagolytic, tachycardia->bradycardia)
Hypotension/tachycardia: Atracurium and mivacurium (because of histamine release)
Vagolytic: Pancuronium (slight catecholamine release/indirect sympathomimetic) -> tachycardia (no BP change)
Tachycardia: Usually slight with succinylcholine, repeat dosing in adults/any dose in children can produce sudden bradycardia
Effects of stimulation of histamine receptors by NMBDs
Increased capillary permeability Bronchoconstriction Increased gastric acid production Systemic and cerebral vasodilation Positive inotropic and chronotropic Negative dromotropic (slow conduction)
Prophylaxis against histamine release
Block H1 and H2 receptors
H1: Benadryl
H2: Zantac
Factors related to anesthesia that might prolong paralysis
Cholinesterase deficiency or variance Hypothermia Steroids Volatile anesthetics Dantrolene
Antibiotics, muscle relaxants, neostigmine, and calcium
Abx can cause neuromuscular blockade without NMBDs
-When combined with NMBDs they can potentiate block
(cephalosporin’s and penicillin’s haven’t been reported to potentiate block)
Neostigmine sometimes doesn’t work, and calcium shouldn’t be used to speed recovery
Wait until block terminates spontaneously
Intubating dose of Vecuronium, time to onset, and duration of action
0.1 mg/kg
Onset: 2-4 minutes
Duration of action: 30-60 minutes
Intubating dose of Cisatracurium, time to onset, and duration of action
0.1 mg/kg
Onset: 2-4 minutes
Duration of action: 30-60 minutes
Intubating dose of Rocuronium, time to onset, and duration of action
0.6-1.2 mg/kg (RSI=1.2 mg/kg)
Onset: 1-1.5 minutes
Duration of action: 30-60 minutes
Intubating dose of Succinylcholine (& RSI dose), time to onset, and duration of action
1-1.5 mg/kg (100 mg is standard)
RSI: 2 mg/kg
Onset: 30-60 seconds
Duration of action: 5-15 minutes
Time frame since NMBDs were given when reversal should still be given
If time since relaxant was given is <4 hours reversal should be given
Neostigmine dose, onset, duration, common side effect
Dose: .05 mg/kg (25-75mcg/kg)
Onset: 5-15 minutes
Duration: 45-90 minutes
May increase PONV
Edrophonium dose, onset, duration, indication
Dose: .5-1 mg/kg
Onset: 5-10 minutes (faster than neostigmine)
Duration: 30-60 minutes
Indication: Lower efficacy, only works if block is already wearing off (not for deep block), rapid onset
Atropine with reversal dose, onset, duration, indication
Dose: 15 mcg/kg Onset: 1-2 minutes Duration: 1-2 hours Indication: Anti muscarinic, given with edrophonium (more rapid onset) *Crosses BBB
Glycopyrrolate with reversal dose, onset, duration, indication
Dose: 10-20 mcg/kg Onset: 2 minutes Duration: 2-4 hours Indication: Anti muscarinic, given with neostigmine (not fast enough onset for edrophonium), less initial tachycardia than atropine *No CNS effects (doesn't cross BBB)
Sugammadex general dosing, onset, duration, indication
Dose: 2-8 mg/kg (up to 16 safely used)
Onset: 1-2 minutes
Duration: 2-16 hours
Indication: Reversal of steroidal NMBDs (works better for roc than vec)
Sugammadex specific dosing based on To4
Immediate roc RSI: 16 mg/kg
1-2 PTC after 5 seconds tetanus: 4 mg/kg
To4 second twitch: 2 mg/kg (most common dose)
To4 ratio of 0.5: 0.22 mg/kg
Max doses of neostigmine and edrophonium
Neostigmine: 5mg
Edrophonium: 1 mg/kg
100% of cholinesterase inhibited at these doses
Neostigmine mechanism of action
Normal process: Cholinesterase binds to acetylcholine in synapse and metabolizes it
Neostigmine: Attaches to cholinesterase in the synapse so it metabolizes it instead of acetylcholine (takes 45 minutes to metabolize vs seconds for acetylcholine), acetylcholine builds up in the synapse more than the muscle relaxant to bind to receptors
Sequence of muscles to get paralyzes
1: Eye lids
2: Extremities
3: Chest/intercostals
4: Abdominal muscles
5: Diaphragm
* Muscle function returns in the opposite order
Train of four ratio to be considered “recovered”
90%
Percent paralysis when train of four results are..
4/3/2/1/0 twitches
4 twitches: <70% 4 twitches (with To4 ratio<90%): 70-75% 3 twitches: 75-80% 2 twitches: 80-85% 1 twitch: 90-95% 0 twitches: 100%
“Fade” on train of four (why it happens, what it means)
Normal physiology: to sustain a muscle contraction there is a positive feedback mechanism on the presynaptic acetylcholine receptors to continue releasing acetylcholine
Nondepolarizing muscle relaxants block these presynaptic receptors
Unique train of four results for succinylcholine
No fade, called a “sustained response”
- Will have 4 twitches but they will all get smaller and smaller until no twitch
- Can’t get a train of four ratio
Posttetanic potentiation/stimulation/facilitation
Exaggerated response to twitches after tetanus hold (doesn’t happen with succs)
Pretreating succs with non depolarizer (why do you do it, what happens to the dose you need to give)
Given to prevent fasciculations
-Antagonize block, need to give ~20% more succs
Anticholinesterase drugs and succinylcholine
Block is potentiated
Succinylcholine relies on metabolism by cholinesterase just like AcH
