Regional block and mexiletine: the effect on pain after cancer breast surgery. (St. Savas Hospital, Athens, Greece) Reg Anesth Pain Med 2001;26:223–228.
Authors: Fassaoulaki Argyro , Sarantopoulos Constantine , Melemeni Aikaterini 
Published: March 2003

This study investigated the effect of regional block, oral mexiletine, and the combination of both, on acute and chronic pain associated with cancer breast surgery. One hundred patients scheduled for cancer breast surgery received either regional block with 18 mL of 1% ropivacaine intraoperatively and oral mexiletine for the first 6 postoperative days or regional block and placebo (R + PL), or normal saline instead of ropivacaine and mexiletine (PL + M), or normal saline and placebo (PL + PL). Postoperative analgesic requirements were recorded daily. Pain was assessed 0, 3, 6, 9, and 24 hours in the postanesthesia care unit and on the 2nd to 6th day postoperatively, at rest, and after movement using the visual analog scale. Three months after surgery, the patients were interviewed for the presence and intensity of pain, abnormal sensations, and analgesic requirements. Regional block reduced the number of intramuscular injections required the first 24 hours with the R + PL group requiring less injections versus the PL + M group. Three months after surgery, the 4 groups were similar with regard to incidence or intensity of pain or analgesic requirements. The R + PL group has a lower incidence (77%) of reduced or absent sensation. Conclude that regional block reduced the analgesic requirements in the early postoperative period, while mexiletine combined with regional block reduced the total analgesic requirements during the next 5 postoperative days.

Comment by Pedro F. Bejarano, M.D. This study illustrates that statistical significance may not necessarily mean clinical significance. Some conclusions of this DB randomized controlled trial goes along with current knowledge in acute pain management:

First, although somehow controversial from the standpoint of the global postoperative outcome, there is great consensus on the concept that regional anesthesia may provide better pain relief in the early postoperative period as compared with systemic analgesia. Secondly, combined analgesia (regional + systemic) may further enhance this benefit, and in the lack of evidence of a specific “pre‐emptive” effect of a sodium‐channel blocker like mexiletine, we wisely assume that the lower pain scores obtained in the first 5 postoperative days of this combination represents such a systemic combined analgesic effect. Third, the statistical difference favoring superior analgesia at three‐hours postoperative period in the regional + placebo over the regional + mexiletine groups can only be explained in the basis of a difference in extension and/or nerve block depth due to technical difficulties or anatomical differences within the groups.

Conversely to the previous conclusions, the suggested aethiological‐correlation of the statistical difference favoring the regional + mexiletine group in the diminished frequency of hypoesthesia remains doubtful, facing the known correlation of this symptom as a direct consequence of the surgical neural tissue damage. To our knowledge, there is no theoretical basis for making such an assumption, and even less from a study on which the power and alfa‐error calculations of the sample were made on the grounds of finding analgesic dosing differences.