Purpose: Identification of novel therapeutics to accelerate acute fracture healing remains critical. A prostaglandin EP-2 receptor agonist (CP-533,536) has demonstrated acceleration of fracture healing in preclinical models. Method: In a phase II randomized, blinded, placebo-controlled trial the efficacy of a single local injection of three doses of CP-533,536 (0.5mg, 1.5mg and 15mg) was compared to both placebo and a standard of care arm in patients with closed tibial shaft fractures treated with reamed inter-locked intramedullary nails. Patients were followed at two week intervals to six months with a final evaluation at one year. Fracture healing was independently adjudicated by a radiologist panel and an orthopedic surgeon panel. Results: Ninety-nine patients were enrolled ranging in age from 17–76 years. Baseline characteristics were comparable across treatment groups. No statistically significant differences in median healing time between any of the CP-533,536 treatment groups and placebo were observed based on radiology panel assessment, however significant differences were demonstrated by an orthopedic panel. At weeks eight, 10, 12, 14 and 16 a higher percentage of subjects in the CP-533,536 1.5 and 0.5 mg groups were considered healed compared to the placebo and the 15 mg groups by the orthopedic panel assessment. Moreover, the CP-533,536 – 0.5 mg group showed a statistically higher (p≤0.05) mean radiographic healing score than placebo treated group at weeks eight, 14, 16, 18, and 24. Conclusion: CP-533,536 demonstrated accelerated healing in patients with acute tibia fractures by an orthopedic panel. Confirmatory trials are required to assure validity of the observed treatment effects

Objective: To assess the effectiveness of intrathecal fentanyl in the relief of post operative pain in patients undergoing lumbar decompression or fusion. Morphine has been shown to be effective intrathecally in spinal surgery but there is an increased incidence of respiratory complications. Fentanyl has not been formally evaluated in this setting. Design: This was a prospective randomized double blind trial. All patients received our standard analgesic regime with PCA via a syringe driver. They were also randomized to receive either 15 micrograms of fentanyl intrathecally, or nothing. The fentanyl was administered by the operating surgeon (GM) under direct vision one or two levels above the site of operation at the end of the procedure. Subjects: 30 patients undergoing lumbar spinal surgery were prospectively recruited. Outcome measures: VAS pain scores were taken at 2, 4, 24 and 48 hours post operatively. Time to first bolus delivery of morphine from the PCA was also recorded as was the total dose of morphine required. Results: The patients randomized to receive fentanyl showed a significant increase in the time to first bolus delivery of morphine as well as a 40% reduction in the total morphine dose delivered. There was also a decrease in their mean VAS scores. There was no increased incidence of side effects in the group receiving fentanyl. No patients suffered respiratory compromise requiring treatment and only 2 patients required HDU observation overnight. The rest of the cohort left recovery after 2 hours to be nursed on an open ward. Conclusion: Intrathecal fentanyl is effective at reducing morphine use via a PCA and mean pain VAS scores after lumbar spinal surgery. We would support its use over intrathecal morphine because of the reduced incidence of respiratory complications and the ability to nurse patients on the open ward

Study Design: Prospective randomized double blind trial. Objective: To assess the effectiveness of intrathecal fentanyl in the relief of post operative pain in patients undergoing lumbar decompression or fusion. Summary of Background Data: Morphine has been shown to be effective intrathecally in spinal surgery but there is an increased incidence of respiratory complications. Fentanyl has not been formally evaluated in this setting. Methods: All patients received our standard analgesic regime with PCA via a syringe driver. They were also randomised to receive either 15 micrograms of fentanyl intrathecally, or nothing. The fentanyl was administered by the operating surgeon under direct vision one or two levels above the site of operation at the end of the procedure. Subjects: 30 patients undergoing lumbar spinal surgery were prospectively recruited. Outcome measures: VAS pain scores were taken at 2, 4, 24 and 48 hours post operatively. Time to first bolus delivery of morphine from the PCA was also recorded as was the total dose of morphine required. Results: The patients randomized to receive fentanyl showed a significant increase in the time to first bolus delivery of morphine as well as a 40% reduction in the total morphine dose delivered. There was also a decrease in their mean VAS scores. There was no increased incidence of side effects in the group receiving fentanyl. No patients suffered respiratory compromise requiring treatment and only two patients required HDU observation overnight. The remainder of the cohort left recovery after 2 hours to be nursed on an open ward. Conclusion: Intrathecal fentanyl is effective at reducing morphine use via a PCA and mean pain VAS scores after lumbar spinal surgery. We would support its use over intrathecal morphine because of the reduced incidence of respiratory complications and the ability to nurse patients on the open ward