Optimising the therapeutic use of local anaestehetics. From microdialysis of the rat spinal cord to a clinical investigation and liposomal encapsulation.

Samenvatting

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 bupivacaine-encapsulated 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.

Datum prijs	4 jun. 2009
Originele taal	English
Prijsuitreikende instantie	Vrije Universiteit Brussel
Begeleider	Jan Poelaert (Promotor), Ilse Smolders (Promotor), Brigitte Velkeniers-Hoebanckx (Jury), Guy Ebinger (Jury), Pierre Van Den Brande (Jury), Christian Verborgh (Jury), Jean Marc Malinosky (Jury), Jean-François Brichant (Jury), Maurice Sosnowski (Jury), Eric Mortier (Jury) & Marcel Vercauteren (Jury)