Reversal of Neuromuscular Blockade

Question 1

Regarding objective monitoring of neuromuscular block, which one of these statements is correct?

A. The electromyograph records the action potential in the ulnar nerve
B. The acceleromyograph uses a strain gauge transducer
C. A target value of TOF 0.7 is considered adequate for recovery of neuromuscular function
D. The double burst stimulus comprises a total of 2 nerve stimuli
E. Comparison of fourth twitch in the train (T4) to the first twitch in the train (T1) yields a TOF ratio

Answer 1

E.

A. Incorrect. It records the action potential in the muscle.
B. Incorrect. It uses a piezo-electric crystal.
C. Incorrect. TOF 0.9 is the desired parameter.
D. Incorrect. DBS comprises 2 bursts each having 3 stimuli.

Question 2

What are clinical ways of assessing residual block?

Answer 2

Sustained head lift for five seconds - be mindful that patients can achieve this at a TOF ratio of 0.6.
Tidal volume size
Tongue protrusion and grip

Question 3

At what percentage of the original twitch amplitude of T1, will T4, T3 and T2 disappear?

Answer 3

T4 - 25%
T3 - 15-20%
T2 - 5-10%

Question 3

When is the earliest time (in terms of number of twitches present and amplitude of the twitches) that reversal of neuromuscular block with an acetylcholinesterase inhibitor can be achieved safely?

Answer 3

If it is administered when the twitch (TOF) count is 2 or greater

Question 4

What percentage of Ach receptors must be blocked for T1 twitch to disappear?

Answer 4

> 90%

Question 5

With regards to the assessment of neuromuscular block (true or false):

A sustained head lift guarantees full recovery of neuromuscular function

Answer 5

False. Sustained head lift can occur with a TOF ratio of <0.6.

Question 6

With regards to the assessment of neuromuscular block (true or false):

Mechanomyography is an assessment tool in routine clinical practice

Answer 6

False. It is primarily a research tool. Acceleromyography is the objective assessment tool more likely to be encountered in clinical practice.

Question 7

With regards to the assessment of neuromuscular block (true or false):

When using a peripheral nerve stimulator to assess residual neuromuscular block, double burst stimulation is more accurate than train of four

Answer 7

True. DBS is superior to train of four in the visual and tactile assessment of fade. However, acceleromyography is superior to both.

Question 8

With regards to the assessment of neuromuscular block (true or false):

When using acceleromyography to assess residual neuromuscular block, a TOF ratio of 0.9 is the gold standard to be achieved

Answer 8

True

Question 9

With regards to the assessment of neuromuscular block (true or false):

When using a nerve stimulator to assess depth of block, absence of adductor pollicis twitches from ulnar nerve stimulation suggests full neuromuscular block is present in the diaphragm

Answer 9

False. The diaphragm has a high density of ACh receptors and is thus more resistant to neuromuscular block than peripheral muscles such as abductor pollicis. In addition, by virtue of its better blood supply it is quicker to recover function than peripheral muscles. However, the absence of twitches at adductor pollicis suggests a sufficient depth of block exists that it would be an unsafe time point at which to administer anticholinesterase reversal agent.

Question 10

Does spontaneous recovery from non-depolarizing neuromuscular block involve (true or false):

Dissociation from the nicotinic acetylcholine receptor

Answer 10

True

Question 11

Does spontaneous recovery from non-depolarizing neuromuscular block involve (true or false):

Hydrolysis by acetylcholinesterase in the junctional cleft

Answer 11

False. It is acetylcholine that is metabolised by AChE in the junctional cleft. The benzylisoquinoliniums undergo hydrolysis, but it is catalysed by plasma cholinesterase (mivacurium) and non-specific esterases (atracurium) and occurs in the plasma.

Question 12

Does spontaneous recovery from non-depolarizing neuromuscular block involve (true or false):

Diffusion to plasma

Answer 12

True

Question 13

Does spontaneous recovery from non-depolarizing neuromuscular block involve (true or false):

Uptake into the nerve terminal

Answer 13

False. Uptake into the nerve terminal occurs for choline, which is the breakdown product of acetylcholine metabolism.

Question 14

Does spontaneous recovery from non-depolarizing neuromuscular block involve (true or false):

Clearance from plasma creates a concentration gradient from NMJ

Answer 14

True.

Question 15

Regarding reversal agents (true or false):

Neostigmine forms a weak hydrogen bond with the esteratic binding site on AChE

Answer 15

False. Edrophonium forms such a bond with which ACh is readily able to compete. As such, edrophonium is little used in clinical practice and only for very shallow degrees of block.

Question 16

Regarding reversal agents (true or false):

Neostigmine reacts with AChE to form a carbamylated enzyme which requires regeneration to yield active enzyme

Answer 16

True. The half-time is 30 minutes.

Question 17

Regarding reversal agents (true or false):

Acetylcholinesterase inhibitors are safely administered as sole agents

Answer 17

False. Anticholinesterases are not specific to the neuromuscular junction. They also block acetylcholinesterase in the autonomic nervous system leading to muscarinic side-effects. They should routinely be co-administered with an antimuscarinic agent.

Question 18

Regarding reversal agents (true or false):

Sugammadex encapsulates rocuronium to cause rapid reversal of neuromuscular block

Answer 18

True. This drug reverses a similar depth of block significantly faster than neostigmine.

Question 19

Regarding reversal agents (true or false):

Sugammadex alone has no action at the NMJ

Answer 19

True

Question 20

Name the two binding sites of acetylcholinesterase.

Answer 20

It possesses anionic and esteratic binding sites.

Question 21

What part of acetylcholine does the anionic site of AChE form a bond with?

Answer 21

The anionic site forms an ionic bond with the quaternary nitrogen atom of ACh.

Once both sites are bound choline is then released from the anionic site leaving acetylated enzyme that is hydrolysed within microseconds producing acetic acid and regenerated enzyme.

Question 22

What part of acetylcholine does the esteratic site of AChE form a bond with?

Answer 22

The esteratic site on the enzyme forms a covalent bond with the acetyl group on ACh.

Once both sites are bound choline is then released from the anionic site leaving acetylated enzyme that is hydrolysed within microseconds producing acetic acid and regenerated enzyme.