Perioperative pregabalin does not reduce opioid requirements in total knee arthroplasty

  • Jing Hui Yik
  • Wei Yang Wilson ThamEmail author
  • Kwang Hui Tay
  • Liang Shen
  • Lingaraj Krishna



The purpose of this prospective, randomized, double-blinded, placebo-controlled study was to determine if pregabalin, when given perioperatively in addition to patient-controlled analgesia morphine, paracetamol and etoricoxib, is effective in reducing morphine requirements and moderating pain scores after primary total knee arthroplasty. We hypothesize that there would be no difference in postoperative opioid requirements, postoperative pain scores, and functional scores with the use of perioperative pregabalin.


Eighty-seven patients who underwent primary total knee arthroplasty were randomised and allocated to two groups. One group received capsules containing pregabalin 75 mg, and the other a placebo—one capsule before surgery and one capsule once per night up till postoperative day 2. Multimodal analgesia provided for all patients in this study included femoral nerve block, intravenous patient-controlled analgesia (morphine), paracetamol and etoricoxib. The primary outcome of patient’s pain control was based on the measurement of cumulative morphine consumption during the first 72 h postoperatively.


Pregabalin did not reduce the cumulative or effective morphine consumption at 48 h and 72 h post-operation. There were also no significant differences noted in pain scores at 48 h and 72 h after surgery, functional range of motion of the operated knee at 72 h post-op, or outcomes recorded on the Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and 36-Item Short Form Survey (SF-36) questionnaires at 3 and 6 months post-op. None of the patients demonstrated common adverse reactions to pregabalin.


This study showed no reduction in postoperative opioid requirements, or improvement in early postoperative pain scores or functional outcomes at 6 months, with perioperative use of pregabalin. Orthopaedic surgeons may consider this when selecting an analgesic regimen for their patients.

Level of evidence



Total knee arthroplasty Pregabalin Morphine Preoperative Analgesia Pain score 







Knee Society Score


Non-steroidal anti-inflammatory drugs


Patient-controlled analgesia


Range of motion


36-Item Short Form Survey


Total knee arthroplasty


Visual Analogue Scale


Western Ontario and McMaster Universities Osteoarthritis Index



We would also like to thank the following surgeons from the National University Hospital, Singapore, for taking part in this trial: Dr. Mark Chong, Dr. Gavin O’Neill, Dr. Diarmuid Murphy, Dr. Gurpal Singh, Prof. Kandiah Satku, Prof. Wilson Wang.


No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to disclose.

Ethical approval

The trial protocol was approved by the institutional review board of the Health Science Authority for clinical trials with an investigational product, and by the Domain Specific Review Board of the National Healthcare Group. The trial was registered with (registration number: NCT02954484).

Informed consent

All patients provided written informed consent.


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Copyright information

© European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2019

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgeryNational University Hospital, National University Health System, SingaporeSingaporeSingapore
  2. 2.Department of AnaesthesiaNational University Hospital, National University Health System, SingaporeSingaporeSingapore
  3. 3.Biostatistics Unit, Yong Loo Lin School of MedicineNational University of Singapore, SingaporeSingaporeSingapore

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