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

Reg Anesth Pain Med. May-Jun 2000;25(3):274-8. doi: 10.1016/s1098-7339(00)90010-5.


Background and objectives: Voltage-sensitive calcium channel conductance is essential for the nervous system to signal a painful event. However, intrathecal administration of L-type calcium channel blockers does not provide analgesia. The present investigation was designed to assess the safety and analgesic efficacy of ziconotide, 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 undergoing elective total abdominal hysterectomy, radical prostatectomy, or total hip replacement. After intrathecal injection of local anesthetic and before surgical incision, a continuous intrathecal infusion of either placebo or 1 of 2 doses of ziconotide (0.7 microg/h or 7.0 microg/h) was started and continued for 48 to 72 hours postoperatively. Primary and secondary efficacy variables were the mean daily patient controlled analgesia (PCA) morphine equivalent consumption and visual analog pain intensity (VASPI) scores, respectively.

Results: Thirty patients received study drug; 26 were evaluable for efficacy. Mean daily PCA morphine equivalent consumption was less in patients receiving ziconotide than in placebo-treated patients, and the difference was statistically significant between 24 and 48 hours (P = .040). VASPI scores during the first 8 hours postoperatively were markedly lower in ziconotide-treated than in placebo-treated patients. In 4 of 6 patients receiving the high-dose of ziconotide (7 microg/h), adverse events, such as dizziness, blurred vision, nystagmus, and sedation contributed to study drug being discontinued after 24 hours. After ziconotide discontinuation, these symptoms resolved.

Conclusions: Ziconotide showed analgesic activity, as shown by decreased PCA morphine equivalent consumption and lower VASPI scores. Because of a favorable trend of decreased morphine consumption with an acceptable side-effect profile in the low-dose ziconotide group, 0.7 microg/h may be closer to the ideal dose than 7 microg/h. Large-scale studies are required to clarify this issue.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesia, Patient-Controlled
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use
  • Arthroplasty, Replacement, Hip
  • Calcium Channel Blockers / administration & dosage
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use*
  • Calcium Channels, N-Type / drug effects
  • Calcium Channels, N-Type / metabolism*
  • Double-Blind Method
  • Female
  • Humans
  • Injections, Spinal
  • Male
  • Middle Aged
  • Morphine / administration & dosage
  • Morphine / therapeutic use
  • Pain Measurement
  • Pain, Postoperative / drug therapy*
  • Pilot Projects
  • omega-Conotoxins / administration & dosage
  • omega-Conotoxins / adverse effects
  • omega-Conotoxins / therapeutic use*


  • Analgesics, Opioid
  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • omega-Conotoxins
  • Morphine
  • ziconotide