Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.

CONTEXT: Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects. OBJECTIVE: To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment. DESIGN, SETTING, AND PATIENTS: Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment. INTERVENTIONS: Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group. MAIN OUTCOME MEASURE: Mean percentage change in VASPI score from baseline to the end of the initial titration period. RESULTS: Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved complete pain relief, and 50.0% of patients receiving ziconotide responded to therapy compared with 17.5% of those receiving placebo (P =.001). CONCLUSION: Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.

A placebo-controlled trial of midazolam as an adjunct to morphine patient-controlled analgesia after spinal surgery.

STUDY OBJECTIVE: To investigate the potential benefit of postoperatively providing a patient-controlled anxiolytic agent, midazolam, in addition to morphine. DESIGN: A double-blinded, placebo-controlled trial of patient-controlled midazolam. SETTING: A Community hospital. PARTICIPANTS: 29 patients undergoing elective spinal surgery. INTERVENTIONS: Postoperatively, via two separate patient-controlled pumps, the treatment group received morphine and midazolam, and the control group received morphine and saline solution. MEASUREMENTS: Repeated measures using numerical rating scales of the primary outcomes of pain and anxiety were obtained every two hours postoperatively. Amount of morphine and midazolam/placebo administered was assessed, as were other secondary outcomes. MAIN RESULTS: Anxiety level in the treatment group declined more rapidly over the 24 hours after surgery than in the control group. The treatment group used less morphine than the control. Preoperative positive affect was the only significant psychological predictor of postoperative outcomes. CONCLUSIONS: Patients who received both midazolam and morphine experienced a more rapid decline in anxiety and used less opioid medication than those receiving morphine alone.