Effect of epinephrine on lidocaine clearance in vivo: a microdialysis study in humans.
BACKGROUND
Local anesthetic nerve block prolonged by epinephrine is thought to result from local vasoconstriction and consequent decreased local anesthetic clearance from the injection site. However, no study has yet confirmed this directly in humans by measuring tissue concentrations of local anesthetic over time. In addition, recent studies have shown that the alpha2-adrenergic receptor agonist, clonidine, also prolongs nerve block without altering local anesthetic clearance. Because epinephrine is also an alpha2-adrenergic receptor agonist, it is possible that epinephrine prolongs local anesthetic block by a pharmacodynamic mechanism and not a pharmacokinetic one. This study was designed to address this issue.


METHODS
Microdialysis probes were placed adjacent to the superficial peroneal nerve in both feet of eight volunteers. Plain lidocaine (1%) was injected along one peroneal nerve and lidocaine with epinephrine (2.5 microg/ml) was injected along the other nerve in a double-blinded, randomized manner. The concentration of lidocaine in tissue was measured at 5-min intervals, and sensory block and cutaneous blood flow were assessed by laser Doppler at 10-min intervals for 5 h. The resulting data for lidocaine concentration versus time were fit to a two-compartment model using modeling software.


RESULTS
Epinephrine prolonged sensory block by decreasing local blood flow and slowing clearance. There was no evidence of a pharmacodynamic effect of epinephrine.


CONCLUSIONS
Although epinephrine activates alpha2-adrenergic receptors, its mechanism for prolonging the duration of local anesthetic block rests on its ability to decrease local anesthetic clearance and not on a pharmacodynamically mediated potentiation of local anesthetic effect.
Bernards
C M
CM
Department of Anesthesiology, University of Washington, Seattle 98195, USA. chrisb@u.washington.edu
Kopacz
D J
DJ
D000328:Adult; D000779:Anesthetics, Local / Q000493:pharmacokinetics* / Q000494:pharmacology; D001825:Body Fluid Compartments; D004311:Double-Blind Method; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D009407:Nerve Block / Q000379:methods; D010543:Peroneal Nerve / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000779:Anesthetics, Local; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D008012:Lidocaine; D004837:Epinephrine