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10 Local anaestheticsKinetics
The onset of action is intermediate or slow and significantly slower than that of lido-
caine. It is the most highly protein bound amide local anaesthetic and is metabolized
in the liver by dealkylation to pipecolic acid and pipecolylxylidine.Levobupivacaine
Levobupivacaine is the S-enantiomer of bupivacaine, which is the racemic mixture
of the S- and R-enantiomer.Presentation and uses
Levobupivacaine is prepared as a 2.5, 5 and 7.5 mg.ml–1solution. It is used in a manner
similar to that of bupivacaine. A maximum single dose of 150 mg is recommended
with a maximum dose over 24 hours of 400 mg.Toxicity profile
The single advantage of levobupivacaine over bupivacaine and other local anaes-
thetics is its potential for reduced toxicity. While extrapolation of research from ani-
mal models to humans may be confusing, combined with limited human volunteer
work it appears that levobupivacaine has two potentially useful properties. First, the
dose required to produce myocardial depression (by blocking cardiac K+channels)
is higher for levobupivacaine compared with bupivacaine, and second, excitatory
central nervous system effects or convulsions occur at lower doses with bupivacaine
than levobupivacaine.Ropivacaine
Presentation and uses
The amide local anaesthetic ropivacaine is prepared in three concentrations (2, 7.5
and 10 mg.ml−^1 ), in two volumes (10 and 100 ml) and as the pure S-enantiomer. It is
not prepared in combination with a vasoconstrictor as this does not alter its duration
of action or uptake from tissues. The R-enantiomer is less potent and more toxic. It
has a propyl group on its piperidine nitrogen in contrast to the butyl group present
in bupivacaine and the methyl group present in mepivacaine (Figure10.3).
The main differences from bupivacaine lie in its pure enantiomeric formulation,
improved toxic profile and lower lipid solubility. Its lower lipid solubility may result
in reduced penetration of the large myelinated Aβmotor fibres, so that initially these
fibres are relatively spared from local anaesthetic. However, during continuous infu-
sion they too will become blocked by local anaesthetic resulting in similar degrees
of block between Aβfibres and the smaller unmyelinated C fibres. Therefore, the
motor block produced by ropivacaine is slower in onset, less dense and of shorter
duration when compared with an equivalent dose of bupivacaine. Theoretically it