Neuromuscular Blocking Agents

Question 1

Explain what happens at the neuromuscular junction to cause muscle contraction.

Answer 1

1. An action potential travels down a motor neuron to the presynaptic terminal.
2. Voltage-gated calcium channels open and cause vesicles of acetylcholine to release into the synaptic cleft.
3. Acetylcholine binds to acetylcholine-gated receptor channels (nicotinic receptors) at the motor end plate (post-synaptic membrane)
4. Na+/K+ ion channels open causing an influx of sodium and eflux of potassium creating an action potential. The action potential depolarizes the skeletal muscle and causes it to contract.
5. Acetylcholine is then degraded by acetylcholinesterase into acetate and choline. Choline can be used to make more acetylcholine.

Question 2

How does succinylcholine work?

Answer 2

-succinylcholine (anectine) is 2 acetylcholine molecules that overwhelms the synaptic cleft & binds to nicotinic receptors on the motor end plate

-depolarizing neuromuscular blocking agent - depolarizes motor end plate until it reaches an absolute refractory period (muscles fatigue out)

Question 3

Side effects of succinylcholine

Answer 3

-hyperkalemia - will cause a transient release of K+ to be released into circulation (0.5-1.0 mEq/L)

-myalgias - severe muscle contractions (fasiculations). patients may feel like they worked out. Can elevate ICP

Question 4

normal dose of succinylcholine

Answer 4

1 - 2 mg/kg IV

2-4 mg/kg IM

Question 5

onset & duration of succinylcholine

Answer 5

onset: 30 sec

duration 5 - 10 minutes (good for difficult airways because you can BVM until it wears off)

Question 6

elimination of succinylcholine

Answer 6

enzymatically hydrolyzed by plasma cholinesterase/pseudocholinesterase/butyrocholinesterase

Acetylcholine is hydrolyzed by true cholinesterase, which is found at the neuromuscular junction as well as at tissues innervated by parasympathetic nerves.

Question 7

List five conditions that may accentuate succinylcholine-induced hyperkalemia

Answer 7

1. Unhealed third-degree burns
2. denervation of skeletal muscle (paraplegia or hemiplegia)
3. severe skeletal muscle trauma
4. upper motor neuron injury (head injury, Parkinson’s disease, cerebrovascular accident)

5.muscular dystrophy

Question 8

Why is succinylcholine contraindicated in patients with nerve damage?

Answer 8

When motor nerves to skeletal muscle are damaged, nicotinic receptors of the skeletal muscle cell up regulate. These extrajunctional cholinergic (nicotinic) receptors on skeletal muscle are exceptionally responsive to succinylcholine. Potassium leaves the cell in excessive quantities when succinylcholine triggers these channels to open. and hyperkalemia results

Question 9

How do non-depolarizing neuromuscular blocking medications work?

Answer 9

Non-depolarizing NMB are competitive antagonists to acetylcholine. They prevent depolarization by binding to nicotinic receptors on the motor end plate.

Question 10

What are the 2 classifications of non-depolarizing muscle relaxants?

Answer 10

benzylisoquinoliniums (-curium)
-cisatracurium (nimbex), atracurium (tracrium)

steroid derivatives (-curonium)
-vecuronium (norcuron), rocuronium

Question 11

What is the termination of the action of non-depolarizing muscle relaxants usually due to?

Answer 11

Redistribution to non-muscle tissues is the major cause of the initial decrease in concentration of relaxant at the neuromuscular junction

Question 12

How are benzylisoquinoliniums eliminated?

Answer 12

Hofmann elimination - good for kidney/liver patients

Question 13

Hofmann elimination is dependent on what two factors? What body conditions are necessary for Hofmann elimination of atracurium or cisatracurium to occur?

Answer 13

Hofmann elimination is temperature and pH dependent. Hofmann elimination occurs in the presence of physiologic pH (7.4). The rate of Hofmann elimination is slowed by acidosis (pH<7.4) or decreases in body temperatures (<37 degrees C). Hofmann elimination is increased with an increase in pH or body temperature.

Question 14

How are steroid derivative non depolarizing NMB eliminated?

Answer 14

biliary excretion (primary) and some renal excretion (secondary) and some metabolism (secondary).

Question 15

What is the dose for vecuronium?

Answer 15

0.8 mcg/kg/min

Question 16

What is the dose for rocuronium?

Answer 16

0.01 - 0.012 mg/kg/min

0.6 - 1.2 mg/kg for RSI

Question 17

What is the dose for atracurium?

Answer 17

0.002-0.015 mg/kg/min

Question 18

What is the dose for cisatracurium?

Answer 18

3 mcg/kg/min

Question 19

Why would cisatracurium be preferred over atracurium?

Answer 19

atracurium can cause histamine release causing vasodilation and hypotension.

cisatracurium is cardiac stable

Question 20

What is the onset & duration of rocuronium during RSI?

Answer 20

Onset: 45 - 120 sec

Duration: 30 - 90 minutes

Question 21

Why would maximum doses of anticholinesterase drugs fail to fully reverse nondepolarizing neuromuscular blockade?

Answer 21

1. Insufficient time has elapsed for the anticholinesterase drug to antagonize the muscle relaxant.
2. The degree of neuromuscular blockade is too intense to be antagonized.
3. Body temperature is abnormally low.
4. There is an acid-base or electrolyte disturbance.
5. The patient is receiving drugs that interfere with metabolism
6. Clearance of the nondepolarizing drug is reduced by renal or hepatic disease.

Question 22

At what point is the earliest possible time to reverse a nondepolarizing muscle relaxant?

Answer 22

Reversal should not be attempted until there is at least one detectable twitch. If one twitch in four is present and an acetylcholinesterase inhibitor is administered. 15-30 min is required for the twitch height to reach the preblock state.

Question 23

Why is the ulnar nerve the preferred location for TOF monitoring?

Answer 23

it tells us the level of paralysis at the diaphragm

Question 24

What muscle does the ulnar nerve innervate?

Answer 24

adductor pollicis - will see pinky move

if thumb moves, you are directly stimulating the muscle instead of the nerve (not accurate TOF)

Question 25

How should leads be placed for TOF on the ulnar nerve?

Answer 25

on the wrist opposite of the side of the thumb

black (neg) lead should be placed distal and red (pos) should be proximal

Question 26

What is supramaximal stimulation?

Answer 26

Max output where increasing the output no longer gives a stronger muscle contraction (20% over maximum)

Threshold - minimal output needed to achieve contraction

Submaximal - not strong enough to elicit full contraction

Maximal Stimulation - strong enough to obtain full contraction

Question 27

What will be the TOF response with depolarizing NMB (succinylcholine)?

Answer 27

TOF stimulates all receptors at the same time. Strength of contraction will be stronger over time as the medication is metabolized.

Question 28

What will be the TOF response with non depolarizing NMB?

Answer 28

Will see fade (the first twitch will be stronger than the rest - looks like stairs) because only some of the receptors are being blocked

Question 29

What is a TOF ratio?

Answer 29

% of normal contraction of twitch 4 / % of normal contraction of twitch 1

if there is no 4th twitch, then TOF ratio is 0

Question 30

Even if you have 4/4 twitches with non depolarizing NMB, it is important to know that up to ___ % of receptors can still be blocked.

Answer 30

70%

3/4: 70% blocked
2/4: 80% blocked
1/4: 90% blocked
0/4: up to 100% receptors blocked and giving more paralytic won’t increase the response

Question 31

What medication is used as a non depolarizing NMB antagonist and how does it work?

Answer 31

Neostigmine - inhibits acetylcholinesterase (enzyme that breaks down acetylcholine in the neuromuscular junction)

Less acetylcholinesterase = more acetylcholine = more acetylcholine to outnumber the NMB for nicotinic receptor sites

Question 32

Normal dose of Neostigmine and when do you give it?

Answer 32

0.05 - 0.07 mg/kg

Should give when the patient has 1-2 twitches (if pt has 0 twitches you have no idea how much paralytic is available)

Question 33

Onset and duration of neostigmine

Answer 33

onset: 4 - 8 min

duration: 30 min - 2 hrs

Question 34

How is neostigmine eliminated?

Answer 34

Renal (50%)
Plasma esterases

Question 35

Important side effects of neostigmine?

Answer 35

increasing available acetylcholine increases the parasympathetic response: SLUDGEBM

Salivation, Lacrimation, Urination, Defecation, GI disturbances, Emesis, Bronchoconstriction, myosis (contraction of pupils)

Can also produce vagal stimulation leading to bradycardia

Question 36

What medication is important to give concurrently with neostigmine?

Answer 36

An anticholinergic such as glycopyrulate to counteract the effects of acetylcholine (has the same onset as neostigmine)

Question 37

What medication is used to reverse NMB?

Answer 37

Sugammadex - reversal no matter depth of block

Important to note that this only works for steroidal NMB - “uronium”

works by encapsulating and forming a tight water-soluble complex around the NMB which is then excreted through urine (80% cleared through kidneys in 24 hrs)

Question 38

What is the dose for sugammadex?

Answer 38

2 - 16 mg/kg depending on depth of block

4/4: 2 mg/kg

0/4: 16 mg/kg

Question 39

What are the adverse reactions of sugammadex?

Answer 39

dry mouth, N/V, chills, postural hypotension, dysgeusia (bad taste in mouth)

Question 40

What percentage of nicotinic cholinergic receptors must be blocked for clinically significant paralysis? For intubation?

Answer 40

Paralysis permitting adequate abdominal muscle relaxation occurs when 90% of receptors are blocked (1/4 twitches). On the other hand, the patient is completely flaccid when 99% of the receptors are blocked

Question 41

What is the priming principle for nondepolarizing neuromuscular relaxants?

Answer 41

The priming principle for nondepolarizing neuromuscular relaxants involves administering a subtherapeutic dose of a nondepolarizing agent, typically about 10% of the ED95 (the effective dose needed to achieve 95% receptor blockade). This is done prior to the administration of the full dose. The idea behind the priming principle is to hasten the onset of neuromuscular blockade by initially blocking some of the receptors

Question 42

What is the law of mass action, which is also known as Le Chatelier’s principle? In relation to nondepolarizing NMB

Answer 42

Le Chatelier’s principle, also known as the law of mass action, explains the displacement of nondepolarizing muscle relaxant from postsynaptic receptors as acetylcholine accumulates in response to an anticholinesterase drug. This principle states that if a dynamic equilibrium is disturbed by changing the conditions, the position of equilibrium shifts to counteract the change to reestablish an equilibrium.