Analgesic effect of perioperative duloxetine in patients after total knee arthroplasty: a prospective, randomized, double-blind, placebo-controlled trial
Authors: Yuan Mingcheng , Tang Tingting , Ding Zichuan , Li Hao , Zhou Zongke 
Published: March 2022

Abstract
Background
To investigate the analgesic effect of perioperative use of duloxetine in patients received total knee arthroplasty (TKA).

Method
This prospective randomized, double-blind, placebo-controlled trial study was registered in the Chinese Clinical Trial Registry (ChiCTR2000033910). 100 patients were finally enrolled. The hospital pharmacy prepared small capsules containing either duloxetine or starch (placebo) which were all identical in appearance and weight (50:50). The 100 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, including rVAS (visual analogue scale at rest) and aVAS (visual analogue scale upon ambulation) throughout the perioperative period. The secondary outcomes included opioid consumption, range of motion, including both active range of motion (aROM) and passive range of motion (pROM) and adverse events. The patients were followed up everyday until 7 days after TKA, afterwards, they were followed up at the time of 3 weeks and 3 months after TKA.

Result
rVAS in duloxetine group were significantly less than placebo group throughout the postoperative period: 4.7 ± 2.3 vs 5.9 ± 2.6 (P = 0.016) at 24 h postoperative; 2.1 ± 1.6 vs 2.8 ± 1.7 (P = 0.037) at 7 days postoperative. In terms of aVAS, similarly, duloxetine group had less aVAS than placebo group throughout the postoperative period: 6.2 ± 2.1 vs 7.1 ± 2.2 (P = 0.039) at 24 h postoperative; 3.3 ± 1.7 vs 4.1 ± 2.0 (P = 0.034) at 7 days postoperative. Patients in duloxetine group consumed significantly less opioids per day than the placebo group: 24.2 ± 10.1 g vs 28.5 ± 8.3 g (P = 0.022) at 24 h postoperative; 2.7 ± 2.5 g vs 4.1 ± 2.6 g (P = 0.007) at 7 days postoperative. aROM in duloxetine group were significantly better than placebo group until postoperative day 6, the aROM became comparable between the two groups: 110.2 ± 9.9° in duloxetine group vs 107.5 ± 11.5° in control group (P = 0.211). In terms of pROM, duloxetine group had significantly better pROM until postoperative day 5, the pROM became comparable between the two groups: 103.8 ± 12.1° in duloxetine group vs 99.5 ± 10.8° in control group (P = 0.064). 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
Several other RCTs have already mentioned the analgesic effect of duloxetine, but not in the immediate postoperative period. In this study, we found duloxetine could reduce acute postoperative pain in the immediate postoperative period 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.