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Optimising the therapeutic use of local anaesthetics. From microdialysis of the rat spinal cord and liposomal encapsulation, to clinical trials

donderdag, 4 juni, 2009 - 17:00
Campus: Brussels Health Campus
Faculteit: Medicine and Pharmacy
auditorium R. Vanden Driessche
Vincent Umbrain
doctoraatsverdediging

Local anaesthetics (lidocaine, levobupivacaine,
ropivacaine, bupivacaine) are useful analgesics.
Administered for neuraxial or for nerve blockade,
their use may however lead to harmful side
effects.

We studied mechanisms and local side effects of
local anaesthetics after intrathecal administration
of lidocaine or levobupivacaine. We found
transient increases of PGE2, glutamate, aspartate
and taurine in CSF dialysates in a in vivo spinal
cord microdialysis setting of the rat. We
suggested a relation with the clinically observed
transient neurologic symptoms which is
sometimes observed after intrathecal lidocaine
administration.

We selected the most appropriate liposome type
for neuraxial administration after a study of their
extradural biodisposition in rats. In humans, pain
relief and levels in plasma and in CSF after
epidural administration of bupivacaineencapsulated
liposomes showed the limitations of
our formulation and incited to further research.

We also investigated the most suitable
ropivacaine dose for cervical plexus block. Doses
of 225 mg or 150 mg did not show more toxicity
than 112.5 mg but delivered a better quality of
block both for the patient and the surgeon.