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BJA Advance Access originally published online on February 28, 2009
British Journal of Anaesthesia 2009 102(4):540-545; doi:10.1093/bja/aep035
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© The Author [2009]. Published by Oxford University Press on behalf of The Board of Directors of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Comparison of the effects of intrathecal administration of levobupivacaine and lidocaine on the prostaglandin E2 and glutamate increases in cerebrospinal fluid: a microdialysis study in freely moving rats

V. J. Umbrain1,*, M.-H. Lauwers1, L. Shi1, I. Smolders2, Y. Michotte3 and J. Poelaert1

1 Department of Anaesthesia
2 Department of Pharmacology
3 Department of Pharmaceutical Chemistry and Drug Analysis, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium

* Corresponding author. E-mail: vincent.umbrain{at}uzbrussel.be

Background: Bupivacaine has a lower incidence of transient neurological symptoms than lidocaine after intrathecal (i.t.) injection. The increased toxic potential of lidocaine does not support its use in the clinical setting and could be related to augmented levels of spinal prostaglandin E2 (PGE2). We tested whether levobupivacaine leads to lower PGE2 levels than lidocaine. Moreover, we compared the release of PGE2 and glutamate after i.t. injections of levobupivacaine or lidocaine.

Methods: Rats were anaesthetized for implantation of an i.t. dialysis catheter. This allowed sampling dialysates of cerebrospinal fluid (CSF) for measuring PGE2 and glutamate levels. The microdialysis setting included baseline sampling and was followed by an i.t. injection of levobupivacaine 250 µg, 100 µg, or saline. PGE2 and glutamate levels in CSF were analysed for 4 h. In addition, the residual effect of a second i.t. injection on, respectively, of PGE2 and glutamate changes was compared after injection of either 250 or 100 µg levobupivacaine, 1000 or 400 µg lidocaine, or saline.

Results: Prolonged spinal PGE2 increases lasting 50–120 min were observed after levobupivacaine injection. Higher PGE2 concentrations were observed after the second lidocaine 1000 µg injection. Glutamate release after the second injection did not vary between the local anaesthetic groups.

Conclusions: Spinal PGE2 levels are similarly increased after i.t. levobupivacaine injection of 250 and 100 µg. A higher PGE2 response was observed after a second i.t. injection in the animals receiving 1000 µg lidocaine than those receiving 400 mg lidocaine or either dose of levobupivacaine.

Keywords: measurement techniques, microdialysis; pharmacology, lidocaine, levobupivacaine, prostaglandins, glutamate


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