Tramadol hydrochloride/acetaminophen combination versus non-steroidal anti-inflammatory drug for the treatment of perioperative pain after total knee arthroplasty: A prospective, randomized, open-label clinical trial

J Orthop Sci. 2016 Sep;21(5):625-9. doi: 10.1016/j.jos.2016.07.011. Epub 2016 Aug 13.


Background: While many of the commonly used treatments for perioperative pain after total knee arthroplasty (TKA) have been recognized as effective, there is still insufficient evidence for oral medication. In orthopedics, non-steroidal anti-inflammatory drugs (NSAIDs) have been commonly used for perioperative pain; however, serious adverse events have been reported. Conversely, tramadol hydrochloride/acetaminophen combination (TRAM/APAP) therapy has been shown to reduce pain, particularly for chronic pain in Japan. This study aimed to determine TRAM/APAP efficacy in comparison with NSAIDs for perioperative pain after TKA.

Methods: Two hundred eighty patients were enrolled in this study; 137 patients were treated with TRAM/APAP, and 143 patients were treated with NSAID from postoperative (PO) day 2. The primary endpoint was a comparison between the pain visual analog scale (VAS) change from baseline (PO day 2) and PO day 4, day 7, day 10, and day 14. The second endpoint was the number of days until the patient achieved independence from cane walking.

Results: Analysis of endpoints included 130 and 139 patients in the TRAM/APAP and NSAID groups, respectively. The pain VAS change in the TRAM/APAP group on any of the measurement days was significantly improved compared with the NSAID group (P < 0.01). Similarly, the TRAM/APAP group achieved cane-walking independence significantly faster than the NSAID group (P < 0.01).

Conclusion: Efficacy for perioperative pain management after TKA of TRAM/APAP was shown to be superior to that of NSAID; TRAM/APAP was also effective in improving the progress of rehabilitation.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acetaminophen / administration & dosage*
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Arthroplasty, Replacement, Knee / adverse effects
  • Arthroplasty, Replacement, Knee / methods*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Male
  • Osteoarthritis, Knee / surgery
  • Pain Measurement
  • Pain, Postoperative / diagnosis
  • Pain, Postoperative / drug therapy*
  • Patient Satisfaction / statistics & numerical data
  • Prospective Studies
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Tramadol / administration & dosage*
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Drug Combinations
  • Acetaminophen
  • Tramadol