Effect of clonidine on lidocaine clearance in vivo: a microdialysis study in humans.
BACKGROUND
The addition of clonidine to local anesthetics has been shown to prolong both peripheral and central neuraxial local anesthetic blocks. Whether clonidine prolongs local anesthetic block by a pharmacokinetic effect or a pharmacodynamic effect is unclear. By directly measuring lidocaine tissue concentrations at the site of injection in the presence and absence of clonidine, this study was designed to address this question.


METHODS
Microdialysis probes were placed adjacent to the superficial peroneal nerve in both feet of seven volunteers. Plain lidocaine (1%) was injected along one nerve, and lidocaine with clonidine (10 microg/ml) was injected along the other nerve in a double-blind, randomized manner. The extracellular fluid was then sampled for lidocaine concentration at 5-min intervals using microdialysis, cutaneous blood flow was assessed by laser Doppler at 10-min intervals, and sensory block was assessed every 10 min until resolution.


RESULTS
Consistent with previous studies, clonidine prolonged lidocaine sensory block. Blood flow increased in both groups but was significantly lower in the clonidine group, especially during the first 60 min. Consistent with the lower blood flow, the area under the lidocaine concentration-versus-time curve was significantly greater in the clonidine group during the first 60 min.


CONCLUSIONS
When added to lidocaine, clonidine prolonged peripheral nerve block. The pharmacokinetic data suggest that the mechanism of prolongation is at least in part pharmacokinetic.
Kopacz
D J
DJ
Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington 98111, USA. anedjk@vmmc.org
Bernards
C M
CM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003000:Clonidine / Q000494:pharmacology*; D003080:Cold Temperature; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008012:Lidocaine / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D012039:Regional Blood Flow / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000779:Anesthetics, Local; D008012:Lidocaine; D003000:Clonidine