Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain

Background and Objectives: Voltage-sensitive calcium channel conductance is essential for the nervous system to signal a painful event. However, intra thecal administration of L-type calcium channel blockers does not provide a nalgesia. The present investigation was designed to assess the safety and a nalgesic efficacy of ziconotiae, a new N-type calcium channel blocker, when administered intrathecally to patients with acute postoperative pain. Methods: This randomized, double-blind, pilot study included patients under going elective total abdominal hysterectomy, radical prostatectomy, or tota l hip replacement. After intrathecal injection of local anesthetic and befo re surgical incision, a continuous intrathecal infusion of either placebo o r 1 of 2 doses of ziconotide (0.7 mu g/h or 7.0 mu g/h) was started and con tinued for 48 to 72 hours postoperatively. Primary and secondary efficacy v ariables were the mean daily patient controlled analgesia (PCA) morphine eq uivalent consumption and visual analog pain intensity (VASPI) scores, respe ctively. Results: Thirty patients received study drug; 26 were evaluable for efficac y. Mean daily PCA morphine equivalent consumption was less in patients rece iving ziconotide than in placebo-treated patients, and the difference was s tatistically significant between 24 and 48 hours (P = .040). VASPI scores d uring the first 8 hours postoperatively were markedly lower in ziconotide-t reated than in placebo-treated patients. In 4 of G patients receiving the h igh-dose of ziconotide (7 mu g/h), adverse events, such as dizziness, blurr ed vision, nystagmus, and sedation contributed to study drug being disconti nued after 24 hours. After ziconotide discontinuation, these symptoms resol ved. Conclusions: Ziconotide showed analgesic activity, as shown, by decreased P CA morphine equivalent consumption and lower VASPI scores. Because of a fav orable trend of decreased morphine consumption with an acceptable side-effe ct profile in the low-dose ziconotide group, 0.7 mu g/h may be closer to th e ideal dose than 7 mu g/h. Large-scale studies are required to clarify thi s issue.