The Efficacy and Safety of Nonsteroidal Anti-Inflammatory Drugs in Total Joint Arthroplasty: Systematic Review and Direct Meta-Analysis

J Arthroplasty. 2020 Oct;35(10):2739-2758. doi: 10.1016/j.arth.2020.05.035. Epub 2020 May 28.


Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have become widely used to manage perioperative pain following total joint arthroplasty (TJA). The purpose of our study is to evaluate the efficacy and safety of NSAIDs in support of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Management.

Methods: Databases including MEDLINE, EMBASE, and the Cochrane Central Registry of Controlled Trials were searched for studies published prior to November 2018 on NSAIDs in TJA. Studies included after a systematic review evaluated through direct comparisons and/or meta-analysis, including qualitative and quantitative heterogeneity testing, to evaluate effectiveness and safety of NSAIDs.

Results: After critical appraisal of 2921 publications, 25 articles represented the best available evidence for inclusion in the analysis. Oral selective cyclooxygenase (COX)-2 and non-selective NSAIDs and intravenous ketorolac safely reduce postoperative pain and opioid consumption during the hospitalization for primary TJA. Administration of an oral selective COX-2 NSAID reduced postoperative opioid consumption after discharge from TKA.

Conclusion: Strong evidence supports the use of an oral selective COX-2 or non-selective NSAID and intravenous ketorolac as adjunctive medications to manage postoperative pain during the hospitalization for TJA. Although no safety concerns were observed, prescribers need to remain vigilant when prescribing NSAIDs.

Keywords: ketorolac; nonsteroidal anti-inflammatory drugs; pain management; total hip arthroplasty; total knee arthroplasty.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal* / adverse effects
  • Arthroplasty
  • Humans
  • Ketorolac / therapeutic use
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / etiology
  • Pain, Postoperative / prevention & control
  • Pharmaceutical Preparations*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pharmaceutical Preparations
  • Ketorolac