title: 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.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Kamagaya General Hospital, 929-6 Hatsutomi, Kamagaya, Chiba, 273-0121, Japan. Electronic address: twmutamo@gmail.com.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Mochizuki
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yano
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.affiliation: Department of Orthopaedic Surgery, Kamagaya General Hospital, 929-6 Hatsutomi, Kamagaya, Chiba, 273-0121, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hiroshima
authors.affiliation: Department of Orthopaedic Surgery, Kamagaya General Hospital, 929-6 Hatsutomi, Kamagaya, Chiba, 273-0121, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Takaoka
authors.affiliation: Department of Orthopaedic Surgery, Kamagaya General Hospital, 929-6 Hatsutomi, Kamagaya, Chiba, 273-0121, Japan.
authors.forename: Kosei
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Department of Orthopaedic Surgery, Kamagaya General Hospital, 929-6 Hatsutomi, Kamagaya, Chiba, 273-0121, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koenuma
authors.affiliation: Department of Orthopaedic Surgery, Kamagaya General Hospital, 929-6 Hatsutomi, Kamagaya, Chiba, 273-0121, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Ishibashi
authors.affiliation: Department of Orthopaedic Surgery, Chibanishi General Hospital, Chiba, Japan.
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Shirahata
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D020370:Osteoarthritis, Knee / Q000601:surgery; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy*; D017060:Patient Satisfaction / Q000706:statistics & numerical data; D011446:Prospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014147:Tramadol / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D000082:Acetaminophen; D014147:Tramadol