Pharmacology for Anaesthesia and Intensive Care

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9780521704632c11 CUFX213A/Peck 9780521618168 December 28, 2007 12:5

11 Muscle relaxants and anticholinesterases

Twitch height

(a) (b) (c)

Figure 11.3.Types of neuromuscular block in response to a train-of-four, tetanic stimulus,

repeat train-of-four. (a) Control, no muscle relaxant present; (b) partial depolarizing block,

reduced but equal twitch height, no post-tetanic facilitation; (c) partial non-depolarizing block,

reducing twitch height, fade on tetanic stimulation, post-tetanic facilitation.

Metabolism

AChismetabolized by AChE, which is located on the junctional clefts of the post-

synaptic membrane. AChE has an anionic and an esteratic binding site. The anionic

site binds with the positively charged quaternary ammonium moiety while the ester-

atic site binds the ester group of ACh. At the point of ACh breakdown choline is

released and AChE becomes acetylated. The acetylated enzyme is rapidly hydrolyzed

and acetic acid is produced.

Monitoring neuromuscular block

Muscle relaxants are monitored by examining the effect they have on muscle con-

traction following stimulation of the relevant nerve. Nerve stimulators must generate

a supramaximal stimulus (60–80 mA) to ensure that all the composite nerve fibres are

depolarized. The duration of the stimulus is 0.1 msec. The negative electrode should

be directly over the nerve while the positive electrode should be placed where it

cannot affect the muscle in question.

There are five main patterns of stimulation that are used and the characteristic

responses observed in the relevant muscle reveal information about the block.

Single twitch stimulation

This is the simplest form of neurostimulation and requires a baseline twitch height for

it to reveal useful information. It should be remembered that no reduction in twitch

height will be observed until 75% of NMJ receptors have been occupied by muscle

relaxant (Figure11.4). This margin of safety exists because only a small number

of receptors are required to generate a summated mini end-plate potential, which

triggers an action potential within the muscle. Partial NMJ block with depolarizing

muscle relaxants (DMRs) and non-depolarizing muscle relaxants (NDMRs) reduce

the height of single twitch stimulation.