Phase 2, Double-blind, Placebo-controlled, Dose-Response Trial of Intravenous Adenosine for Perioperative Analgesia

Background: Adenosine regulates pain transmission by actions at spinal, supraspinal, and peripheral sites, A few studies have suggested that administration of adenosine might be associated with anesthetic- and analgesic-sparing effects. The primary aim of this multicenter study was to determine the dose-response profile of adenosine with respect to perioperative analgesia. Methods: Women undergoing major gynecologic surgery were enrolled. Subjects were randomly assigned to receive one of four doses of adenosine (25, 50, 100, or 200 mu g . kg(-1) . min(-1)) or matching placebo. A dose-escalation cohort approach was followed. Study drug administration was started in the operating room at the time of skin incision and discontinued at the end of surgery. The anesthetic technique was standardized. Postoperative analgesia was provided with a standardized morphine patient-controlled analgesia system. Data were collected in the hospital and after discharge daily through postoperative day 7. Results: A total of 166 subjects received treatment with study drug. 125 received adenosine and 41 received placebo. Except for height, there were no differences between treatment groups with respect to demographic or baseline characteristics. Cumulative opioid use during the initial 24-h period after extubation was not significantly different between treatment groups. There were also no differences between treatment groups with respect to cumulative anesthetic use, intraoperative opioid requirements, pain scores, sedation, time to readiness for discharge from die postanesthesia care unit, time to readiness for discharge from the hospital, opioid-related symptom distress scores, patient satisfaction with pain control, and occurrence of adverse events. Conclusions. There were no differences between placebo and adenosine with respect to efficacy and safety for perioperative analgesia.