Perioperative Use of Pregabalin vs. Duloxetine for Pain Management of Knee Fracture Surgery: A Double-Blind Randomized Clinical Trial.

Background: Effective postoperative pain management, particularly in orthopedic procedures, presents significant challenges. There is increasing evidence supporting the benefits of multimodal analgesia, including the use of gabapentinoids and serotonin norepinephrine reuptake inhibitors (SNRIs), to minimize opioid consumption while effectively managing pain. However, a gold-standard treatment has not been established. Objectives: This study aims to compare the efficacy of duloxetine and pregabalin within a multimodal analgesic regimen for managing postoperative pain and their opioid-sparing effects following knee fracture surgery. Methods: In this double-blind randomized clinical trial (RCT), 54 patients undergoing knee fracture surgery were randomized to receive either 75 mg oral pregabalin or 30 mg duloxetine twice daily, starting at least 24 hours prior to surgery and continuing up to 48 hours postoperatively. Pain severity was assessed at admission and at 6, 12, 24, and 48 hours post-operation. Patients reporting a pain score greater than six on a Numeric Rating Scale (NRS) received intramuscular morphine. Additionally, total opioid dose, associated complications, and drug adverse effects were monitored within the first 48 hours post-surgery. Results: Although there was no statistically significant difference between the duloxetine and pregabalin groups at each time point, the reduction in pain at the 48-hour mark was more pronounced in the duloxetine group compared to the pregabalin group. The duloxetine group required higher doses of morphine on the first day compared to the pregabalin group (3.96 ± 3.20 mg vs. 2.14 ± 2.72 mg, P = 0.022). However, on the second day, opioid rescue was required in three patients in the pregabalin group, whereas no patients in the duloxetine group required rescue. No clinically significant adverse effects were observed in either group. Conclusions: Duloxetine 60 mg per day is an equally effective perioperative alternative to pregabalin 150 mg per day, resulting in a slight increase in rescue opioid administration with equivalent analgesic efficacy during the first 24 hours postoperatively. It demonstrates notable analgesic outcomes with no increased need for opioids between 24 to 48 hours post-surgery.