Background Duloxetine is effective for chronic musculoskeletal and neuropathic pain, but there are insufficient data to recommend the use of antidepressants for postoperative pain. The authors hypothesized that administration of duloxetine for 15 days would reduce pain with ambulation at 2 weeks after total knee arthroplasty. Methods In this triple-blinded, randomized, placebo-controlled trial, patients received either duloxetine or placebo for 15 days, starting from the day of surgery. Patients also received a comprehensive multimodal analgesic regimen including neuraxial anesthesia, epidural analgesia, an adductor canal block, meloxicam, and oxycodone/acetaminophen as needed. The primary outcome was the pain score (0 to 10 numeric rating scale) with ambulation on postoperative day 14. Results One hundred six patients were randomized and analyzed. On day 14, duloxetine had no effect on pain with ambulation; mean pain was 3.8 (SD, 2.3) for placebo versus 3.5 (SD, 2.1) for duloxetine (difference in means [95% CI], 0.4 [−0.5 to 1.2]; P = 0.386). Symptoms potentially attributable to duloxetine discontinuation at study drug completion (nausea, anxiety) occurred among nine patients (duloxetine) and five patients (placebo); this was not statistically significant (P = 0.247). Statistically significant secondary outcomes included opioid consumption (difference in mean milligram oral morphine equivalents [95% CI], 8.7 [3.3 to 14.1], P = 0.002 by generalized estimating equation) over the postoperative period and nausea on day 1 (P = 0.040). There was no difference in other side effects or in anxiety and depression scores. Conclusions When included as a part of a multimodal analgesic regimen for knee arthroplasty, duloxetine does not reduce subacute pain with ambulation.

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We performed a meta-analysis of the English literature to assess the efficacy of four common regimes for thromboembolic prophylaxis after total knee arthroplasty: aspirin, warfarin, low-molecular-weight heparin (LMWH) and pneumatic compression. We reviewed 136 articles and abstracts published between January 1980 and December 1997. Papers not using routine venography and a lung scan or angiography to detect deep-venous thrombosis (DVT) and pulmonary emboli (PE) respectively, were excluded. Of the 136 studies, 23 with 6,001 patients were selected. The incidence of DVT was 53% (1,701/3,214) in the aspirin group, 45% (541/1,203) in the warfarin group, 29% (311/1,075) in the LMWH group, and 17% (86/509) in the pneumatic compression device group. Intermittent pneumatic compression devices and LMWH were significantly better than warfarin (p < 0.0001) or aspirin (p < 0.0001) in preventing DVT. The incidence of asymptomatic PE was 11.7% in the aspirin group (222/1,901), 8.2% (101/1,229) in the warfarin group and 6.3% (24/378) in the pneumatic compression group. No studies with LMWH used routine lung scans. Warfarin and pneumatic compression were significantly better than aspirin in preventing asymptomatic PE (p < 0.05). The incidence of symptomatic PE was 1.3% (23/1,800) in the aspirin group, 0.4% (2/559) in the warfarin group, 0.5% (2/416) in the LMWH group and 0% (0/177) in the pneumatic compression group. No statistically significant difference was noted between the above prophylactic regimes due to the very small incidence of symptomatic PE. Prophylaxis for thromboembolic disease in TKA may have to include a combination of some of the above regimes to incorporate their advantages.