Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial.

The objective was to investigate the effectiveness of cannabis-based medicines for treatment of chronic pain associated with brachial plexus root avulsion. This condition is an excellent human model of central neuropathic pain as it represents an unusually homogenous group in terms of anatomical location of injury, pain descriptions and patient demographics. Forty-eight patients with at least one avulsed root and baseline pain score of four or more on an 11-point ordinate scale participated in a randomised, double-blind, placebo-controlled, three period crossover study. All patients had intractable symptoms regardless of current analgesic therapy. Patients entered a baseline period of 2 weeks, followed by three, 2-week treatment periods during each of which they received one of three oromucosal spray preparations. These were placebo and two whole plant extracts of Cannabis sativa L.: GW-1000-02 (Sativex), containing Delta(9)tetrahydrocannabinol (THC):cannabidiol (CBD) in an approximate 1:1 ratio and GW-2000-02, containing primarily THC. The primary outcome measure was the mean pain severity score during the last 7 days of treatment. Secondary outcome measures included pain related quality of life assessments. The primary outcome measure failed to fall by the two points defined in our hypothesis. However, both this measure and measures of sleep showed statistically significant improvements. The study medications were generally well tolerated with the majority of adverse events, including intoxication type reactions, being mild to moderate in severity and resolving spontaneously. Studies of longer duration in neuropathic pain are required to confirm a clinically relevant, improvement in the treatment of this condition.

The efficacy and safety of three concentrations of levobupivacaine administered as a continuous epidural infusion in patients undergoing orthopedic surgery.

UNLABELLED: We evaluated the efficacy and safety of three concentrations of levobupivacaine infused epidurally as analgesia for patients undergoing orthopedic procedures. Patients undergoing elective hip or knee joint replacement were enrolled in the study (n = 105). Sensory blockade was established preoperatively with 10-15 mL of 0.75% levobupivacaine. Patients were then randomized to receive 0.0625%, 0.125%, or 0.25% levobupivacaine as a continuous epidural infusion at 6 mL/h for 24 h. IV morphine patient-controlled analgesia was given as rescue analgesia, and time to first request for analgesia and total dose of morphine consumed were recorded. Sensory blockade, motor blockade, visual analog scale pain score, and cardiovascular variables were also recorded at regular intervals postoperatively. Ninety-one patients were included in the primary intent-to-treat analysis. Total normalized dose of morphine, number of patient-controlled analgesia requests, and overall postoperative visual analog scale pain scores were significantly lower for the 0.25% group compared with the other two groups, and the time to first request for rescue analgesia was longer. There was no significant difference between the 0.125% and 0.25% groups in terms of maximum motor blockade achieved and time to minimal motor blockade. Safety data were equivalent among the three groups. We conclude that levobupivacaine as a continuous epidural infusion provided adequate postoperative analgesia and that the 0.25% concentration provided significantly longer analgesia than 0.125% or 0.0625% levobupivacaine without any significant increase in detectable motor blockade relative to the 0.125% group. IMPLICATIONS: Postoperative epidural infusion of levobupivacaine can provide safe and effective analgesia for patients having hip or knee joint replacement. Of the three concentrations we infused at a constant rate, 0.25% provided significantly better pain relief.