Analgesic Effect of Perioperative Duloxetine in Patients After Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Background: To investigate the analgesic effect of perioperative use of duloxetine in patients received total knee arthroplasty (TKA). Method: The hospital pharmacy prepared small capsules containing either duloxetine or starch (placebo) which were all identical in appearance and weight (1:1). Enrolled patients were given a capsule (containing either 60 mg duloxetine or 60 mg placebo) every night before sleep since preoperative day 2 till postoperative day 14 (17 days in all) by a nurse who were not involved in this trial. Other perioperative managements were the same in the two groups. The primary outcome was the VAS score (both rVAS and aVAS) throughout the perioperative period. The secondary outcomes included opioid consumption, range of motion, including both active ROM (aROM) and passive ROM (pROM) and adverse events. Result: rVAS in duloxetine group were significantly less than placebo group throughout the postoperative period (From postoperative 2 hours to postoperative 3 months) (P<0.05). In terms of aVAS, similarly, duloxetine group had less aVAS than placebo group throughout the postoperative period (From postoperative 6 hours to postoperative 3 months) (P<0.05). During the postoperative period (From postoperative day 1 to 7), patients in duloxetine group consumed significantly less opioids per day than the placebo group (P<0.05). aROM in duloxetine group were significantly better than placebo group from postoperative 6 hours to postoperative day 5 (P0.05). In terms of pROM, duloxetine group had significantly better pROM from postoperative 6 hours to postoperative day 4 (P0.05). No significant difference was found between the two groups in the rates of dizziness, bleeding, sweating, fatigue and dryness of mouth. In the placebo group, more patients got nausea/vomiting and constipation (P<0.05). However, in terms of drowsiness, duloxetine group was reported higher rate (P<0.05). Conclusion: Duloxetine could reduce acute postoperative pain and decrease the opioids consumption as well as accelerating postoperative recovery, without increasing the risk of adverse medication effects in patients undergoing TKA. Duloxetine could act as a good supplement in multimodal pain management protocol for patients undergoing TKA. Trial registration statement: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033910). The date of registration was 06/16/2020.