Intraoperative Ketamine and Postoperative Outcomes After Total Knee Arthroplasty: Association with Revision Surgery and Analgesic Use

Abstract Background: Ketamine is widely used as an anesthetic adjunct in total knee arthroplasty (TKA), yet its association with surgical revision and postoperative analgesic exposure remains unclear. Objectives: To evaluate the association between intraoperative ketamine and one-year revision surgery as well as early postoperative analgesic exposure following primary TKA. Methods: We conducted a retrospective, propensity-matched cohort study on the TriNetX Global Collaborative Network. Adults undergoing primary TKA with documented intraoperative ketamine were compared to those without ketamine exposure. Matching used demographic, diagnostic, and perioperative factors. Outcomes included one-year arthroplastic revision, 90-day exposure to any analgesic and specific classes (opioids, NSAIDs, acetaminophen), and prescription counts. Results: After 1:1 matching, 31,575 ketamine-exposed patients were compared with 31,575 controls. Ketamine exposure was associated with higher one-year revision risk (1.7% vs 1.2%; HR 1.38, p<0.001) and increased 90-day exposure to any analgesic (87.3% vs 84.1%; RR 1.04; HR 1.09, p<0.001) and opioids (83.1% vs 79.8%; RR 1.04; HR 1.09, p<0.001), while NSAID exposure was slightly lower (5.3% vs 5.9%; RR 0.90; HR 0.91, p<0.001). The mean number of prescriptions among exposed patients was modestly lower in the ketamine group. Conclusion: In this large multicenter cohort, intraoperative ketamine was associated with greater risks of revision surgery and early postoperative opioid and analgesic exposure. While confounding by indication is possible, these findings raise concerns about ketamine’s long-term impact in TKA. Prospective randomized studies are warranted.