Published online Oct 18, 2025. doi: 10.5312/wjo.v16.i10.110233
Revised: June 27, 2025
Accepted: September 19, 2025
Published online: October 18, 2025
Processing time: 136 Days and 22 Hours
Although opioids and non-steroidal anti-inflammatory drugs are commonly used as preemptive analgesics in total knee arthroplasty (TKA), their side effects are a major concern. Tapentadol, a synthetic opioid analgesic, is noted for its higher potency, lower abuse potential, and better gastrointestinal tolerability compared to traditional opioids. However, its efficacy and safety as preemptive analgesia in TKA have not been evaluated.
To hypothesize that preemptive use of tapentadol significantly reduces posto
Ninety patients undergoing unilateral TKA were randomized to receive either tapentadol (single dose of 100 mg sustained-release, n = 45) or a matched placebo 1 hour before surgery. Postoperative pain was assessed using the visual analog scale (VAS), and total pain reduction scores were recorded. Total rescue analgesic consumption and side effects were monitored for 24 hours. Blood samples were collected 6 hours postoperatively to measure plasma levels of cholecystokinin (CCK) (a potential biomarker of pain) and tapentadol using enzyme-linked im
The baseline characteristics of both groups were comparable. The 24-hour VAS scores, the primary outcome, were significantly lower in the tapentadol group median [interquartile range (IQR)] [1.0 (1.0-3.0)] compared to the placebo group [3.5 (2.0-5.0)]. Significant differences in VAS scores were observed at 4 hours, 6 hours, and 12 hours postoperatively (P < 0.05). Requests for rescue analgesia were significantly delayed in the tapentadol group (P = 0.01), and the total dose of analgesics used was significantly lower [median (IQR): 3 (2-4)] compared to the placebo group [4.5 (3-5), P = 0.001]. No major adverse events were observed in either group. Plasma tapentadol concentrations correlated well with pain intensity, whereas no correlation was found between CCK levels and pain intensity.
A preemptive single dose of 100 mg oral tapentadol is safe, effective, and significantly reduces postoperative pain and rescue analgesic requirements in TKA patients. This approach may reduce opioid dependence and support enhanced recovery protocols.
Core Tip: This randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of a single preemptive 100 mg dose of sustained-release tapentadol in patients undergoing total knee arthroplasty (TKA). Tapentadol significantly reduced postoperative pain scores, delayed the need for rescue analgesia, and lowered total analgesic consumption without increasing opioid-related side effects. Its plasma concentration correlated strongly with pain intensity, while cholecystokinin levels did not. With a favorable safety profile and analgesic efficacy, tapentadol may be a valuable component of multimodal analgesia in TKA, offering an opioid-sparing strategy with reduced gastrointestinal and central nervous system side effects. Further multicenter validation is warranted.