LIDOCAINE CONCENTRATIONS IN PLASMA AND CEREBROSPINAL-FLUID AFTER SYSTEMIC BOLUS ADMINISTRATION IN HUMANS

Preclinical studies suggest that systemic Lidocaine acts at the level of the spinal dorsal horn to inhibit hyperalgesia resulting from nerve injury, yet no clinical data are available to support this view. Ther efore, we sought to characterize the time course of lidocaine in the p lasma and cerebrospinal fluid (CSF) after an IV bolus injection of lid ocaine 2 mg/kg in patients scheduled for surgery involving spinal anes thesia. Sixty-five patients were randomly allocated to one of five stu dy groups (n = 13 per group) receiving IV lidocaine before CSF/plasma sampling at 5, 10, 15, 30, or 60 min. Gas chromatographic analysis of these samples revealed a fast but transient peak (5-15 min) in lidocai ne plasma levels (1.7 +/- 0.16 mu g/mL), which declined rapidly therea fter. Only small concentrations of IV lidocaine were found in the CSF (6%-8% of plasma concentration), but this fraction remained stable fro m 15 min until termination of the experiment. No statistical correlati on was observed between plasma and CSF lidocaine levels. These data su ggest that because of the prolonged availability of lidocaine at the s pinal dorsal horn level, systemic administration of lidocaine suppress es central sensitization within the spinal cord after nerve injury in humans. Implications: Cerebrospinal fluid concentrations of lidocaine after its systemic bolus delivery in humans indicate that the spinal c ord may be the major site of antinociceptive action by this route of d rug administration.