Sodium channel blockers are approved for IV administration in the treatment of neuropathic pain states. Preclinical studies have suggested antihyperalgesic effects on the peripheral and central nervous system. Our objective in this study was to determine the time course of the analgesic and antihyperalgesic mechanisms of perioperative lidocaine administration. Forty patients undergoing major abdominal surgery participated in this randomized and double-blinded study. Twenty patients received lidocaine 2% (bolus injection of 1.5 mg/kg in 10 min followed by an IV infusion of 1.5 mg. kg(-1). h(-1)), and 20 patients received saline placebo. The infusion started 30 min before skin incision and was stopped 1 h after the end of surgery. Lidocaine blood concentrations were measured. Postoperative pain ratings (numeric rating scale of 0-10) and morphine consumption (patient-controlled analgesia) were assessed up to 72 h after surgery. Mean lidocaine levels during surgery were 1.9 +/- 0.7 microg/mL. Patient-controlled analgesia with morphine produced good postoperative analgesia (numeric rating scale at rest, <or=3; 90%-95%; no group differences). Patients who received lidocaine reported less pain during movement and needed less morphine during the first 72 h after surgery (103.1 +/- 72.0 mg versus 159.0 +/- 73.3 mg; Student's t-test; P < 0.05). Because this opioid-sparing effect was most pronounced on the third postoperative day, IV lidocaine may have a true preventive analgesic activity, most likely by preventing the induction of central hyperalgesia in a clinically relevant manner.
Implications: The perioperative administration of systemic small-dose lidocaine reduces pain during surgery associated with the development of pronounced central hyperalgesia, presumably by affecting mechanoinsensitive nociceptors, because these have been linked to the induction of central sensitization and were shown to be particularly sensitive to small-dose lidocaine.