Neuromuscular Blocking Drugs

Question 1

What a patient can do when 50% of their neuromuscular receptors are still occupied

Answer 1

• Head lift
• Sustained bite
• Hand grip
• Inspiratory force >40cmH2O
• Sustained tetanus at 100Hz without fade

Question 2

What a patient can do when still 60-70% of their neuromuscular receptors are occupied

Answer 2

• Sustained tetanus at 50Hz for 5 seconds without fade
• Vital capacity at least 20mL/kg
• Double-burst stimulation without fade

Question 3

What TOF will do when 70-75% receptors are occupied

Answer 3

No palpable fade

Question 4

What patient can do when 80% of receptors are still occupied

Answer 4

Tidal volume of at least 5mL/kg

Question 5

Train of four

Answer 5

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

Question 6

Double-burst stimulation

Answer 6

Two short bursts of 50Hz tetanus separated by 0.75 second

-May be easier to detect fade than To4

Question 7

Tetanus

Answer 7

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

Question 8

Posttetanic count (PTC)

Answer 8

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

Question 9

Clinical duration vs total duration of action of NMBDs

Answer 9

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

Question 10

When is recovery indicated per To4

Answer 10

When the fourth twitch is 90% of the first

Question 11

Chemical structure of succinylcholine, mechanism of action

Answer 11

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

Question 12

Function of cholinesterase, 2 types

Answer 12

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)

Question 13

Dibucaine inhibition test

Answer 13

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)

Question 14

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

Answer 14

• 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)

Question 15

Hyperkalemia and succinylcholine (normal increase, pt population which will increase more)

Answer 15

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

Question 16

Dysrhythmias and succinylcholine

Answer 16

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

Question 17

Malignant hyperthermia and succinylcholine

Answer 17

Succinylcholine triggers MH, not understood why

Question 18

Masseter spasm and succinylcholine

Answer 18

Rare, seen more in children than adults

-Sometimes followed by MH

Question 19

Succinylcholine use in burn patients

Answer 19

Acetylcholine receptors are greatly upregulated post burn for >1 year+, K can rise much higher than 0.5 in these patients, succinylcholine is contraindicated

Question 20

2 chemical structures of non-depolarizing muscle relaxants

Answer 20

Benzylisoquinolines
-Cisatracurium (same as > but doesn’t cause histamine release), atracurium, mivacurium
Steroidal
-Rocuronium, vecuronium, pancuronium

Question 21

Hoffman elimination

Answer 21

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

Question 22

Succinylcholine metabolism

Answer 22

Plasma cholinesterase

Question 23

Cisatracurium metabolism, elimination, and metabolite

Answer 23

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

Question 24

Vecuronium metabolism, elimination, metabolite

Answer 24

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

Question 25

Rocuronium metabolism, elimination, metabolite

Answer 25

Metabolism: <1% Elimination: Kidney 10-25%, Liver 70% Metabolite: None

Question 26

Which NMBDs may be prolonged with renal disease

Answer 26

Pancuronium, rocuronium

Question 27

Which NMBDs may be prolonged with hepatic disease

Answer 27

Rocuronium, vecuronium

Question 28

Which NMBDs will be prolonged with cholinesterase deficiency

Answer 28

Succinylcholine, mivacurium

Question 29

Which NMBDs will cause histamine release

Answer 29

Atracurium and mivacurium, slight release may occur with succinylcholine

Question 30

Cardiac effects of NMBDs (which cause hypotension/tachycardia, vagolytic, tachycardia->bradycardia)

Answer 30

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

Question 31

Effects of stimulation of histamine receptors by NMBDs

Answer 31

``` Increased capillary permeability Bronchoconstriction Increased gastric acid production Systemic and cerebral vasodilation Positive inotropic and chronotropic Negative dromotropic (slow conduction) ```

Question 32

Prophylaxis against histamine release

Answer 32

Block H1 and H2 receptors H1: Benadryl H2: Zantac

Question 33

Factors related to anesthesia that might prolong paralysis

Answer 33

``` Cholinesterase deficiency or variance Hypothermia Steroids Volatile anesthetics Dantrolene ```

Question 34

Antibiotics, muscle relaxants, neostigmine, and calcium

Answer 34

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

Question 35

Intubating dose of Vecuronium, time to onset, and duration of action

Answer 35

0.1 mg/kg Onset: 2-4 minutes Duration of action: 30-60 minutes

Question 36

Intubating dose of Cisatracurium, time to onset, and duration of action

Answer 36

0.1 mg/kg Onset: 2-4 minutes Duration of action: 30-60 minutes

Question 37

Intubating dose of Rocuronium, time to onset, and duration of action

Answer 37

0.6-1.2 mg/kg (RSI=1.2 mg/kg) Onset: 1-1.5 minutes Duration of action: 30-60 minutes

Question 38

Intubating dose of Succinylcholine (& RSI dose), time to onset, and duration of action

Answer 38

1-1.5 mg/kg (100 mg is standard) RSI: 2 mg/kg Onset: 30-60 seconds Duration of action: 5-15 minutes

Question 39

Time frame since NMBDs were given when reversal should still be given

Answer 39

If time since relaxant was given is <4 hours reversal should be given

Question 40

Neostigmine dose, onset, duration, common side effect

Answer 40

Dose: .05 mg/kg (25-75mcg/kg) Onset: 5-15 minutes Duration: 45-90 minutes May increase PONV

Question 41

Edrophonium dose, onset, duration, indication

Answer 41

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

Question 42

Atropine with reversal dose, onset, duration, indication

Answer 42

``` Dose: 15 mcg/kg Onset: 1-2 minutes Duration: 1-2 hours Indication: Anti muscarinic, given with edrophonium (more rapid onset) *Crosses BBB ```

Question 43

Glycopyrrolate with reversal dose, onset, duration, indication

Answer 43

``` 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) ```

Question 44

Sugammadex general dosing, onset, duration, indication

Answer 44

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)

Question 45

Sugammadex specific dosing based on To4

Answer 45

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

Question 46

Max doses of neostigmine and edrophonium

Answer 46

Neostigmine: 5mg Edrophonium: 1 mg/kg 100% of cholinesterase inhibited at these doses

Question 47

Neostigmine mechanism of action

Answer 47

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

Question 48

Sequence of muscles to get paralyzes

Answer 48

1: Eye lids 2: Extremities 3: Chest/intercostals 4: Abdominal muscles 5: Diaphragm * Muscle function returns in the opposite order

Question 49

Train of four ratio to be considered "recovered"

Answer 49

90%

Question 50

Percent paralysis when train of four results are.. | 4/3/2/1/0 twitches

Answer 50

``` 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% ```

Question 51

"Fade" on train of four (why it happens, what it means)

Answer 51

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

Question 52

Unique train of four results for succinylcholine

Answer 52

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

Question 53

Posttetanic potentiation/stimulation/facilitation

Answer 53

Exaggerated response to twitches after tetanus hold (doesn't happen with succs)

Question 54

Pretreating succs with non depolarizer (why do you do it, what happens to the dose you need to give)

Answer 54

Given to prevent fasciculations | -Antagonize block, need to give ~20% more succs

Question 55

Anticholinesterase drugs and succinylcholine

Answer 55

Block is potentiated | Succinylcholine relies on metabolism by cholinesterase just like AcH