This study was performed in order to determine concentration-effect, and graded and quantal dose-response relationships for the clinical administration of intravenous (IV) lidocaine to patients with neuropathic pain. Thirteen patients were administered 500 mg of IV lidocaine at a rate of 8.35 mg/min over 60 min. Visual analog pain scores and venous blood samples were obtained concomitantly at 10 min intervals for 60 min. Blood samples were also obtained for determination of serum and serum water lidocaine concentrations at the onset of analgesia and at the time complete pain relief was attained. Lidocaine concentrations were determined by gas chromatography. Graded dose-response curves were prepared individually and for the group as a whole, and a quantal dose-response curve was prepared for the entire group. The dose-response relationship for IV lidocaine was characterized by large increases in pain relief for concomitant minimal increases in dosage. The difference between the ED50 (372.0 mg) and the ED90 (416.5 mg) was 44.5 mg of lidocaine (5.3 min of infusion). The concentration-effect relationship was also steep with pain scores abruptly decreasing over a range of 0.62 microgram/mL of lidocaine. Interestingly, the free concentration of lidocaine had no better correlation with the onset of analgesia or the attainment of complete analgesia than the serum concentration of lidocaine. This suggests that the mechanism of analgesia to IV lidocaine may not be based upon a conventional concentration-effect relationship. In conclusion, the results of this study suggest that the analgesic response to IV lidocaine is best characterized by a precipitous "break in pain" over a narrow dosage and concentration range.
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