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Opioid-sparing anesthesia based on opioid-free principles for early recovery after total knee arthroplasty: A randomized controlled trial.

Jingwang Liu·Jiaxin Liu·Peng Liu·Wenzhi Li·Mingjie Wang·Jinru Li·Shuhong Yang·Shuang Zhao·Xiuli Wang
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Abstract

OBJECTIVE: To evaluate whether an opioid-sparing anesthesia strategy (OSA), based on opioid-free anesthesia (OFA), improves early postoperative recovery quality and optimizes functional outcomes after total knee arthroplasty (TKA), compared with conventional opioid-based anesthesia (OBA). DESIGN: A randomized controlled trial with blinding of patients, surgeons, and outcome assessors. SETTING: Single center, July 2025 to February 2026. PATIENTS: 98 adult patients scheduled for elective unilateral TKA. INTERVENTION: Patients were randomized to the OSA or OBA group. The OSA regimen used esketamine and dexmedetomidine as the primary analgesic backbone, whereas the OBA regimen was opioid-based. Both groups received preoperative femoral nerve block and were administered oxycodone at skin incision and closure. Postoperatively, both groups received the same multimodal analgesia and patient-controlled analgesia. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. Secondary outcomes included 48-h QoR-15; Oxford Knee Score (OKS) and EQ-5D-3L at 1 and 3 months; high pain at 1 month and chronic postsurgical pain at 3 months. Exploratory outcomes included postoperative C-reactive protein (CRP), and postoperative nausea and vomiting (PONV), among others. RESULTS: At 24 h postoperatively, QoR-15 was higher in the OSA group than in the OBA group (118.4 ± 11.5 vs 113.3 ± 12.2; adjusted difference 5.12, 95% CI 0.51-9.74; P = 0.029), and this advantage persisted at 48 h (adjusted difference 5.54, 95% CI 1.57-9.52; P = 0.007). The OSA group had a lower incidence of PONV (P = 0.025) and lower postoperative CRP levels (P = 0.001). At 1 month, OKS was higher in the OSA group (adjusted difference 2.31, 95% CI 0.34-4.27; P = 0.022), with no significant differences in other secondary outcomes. CONCLUSION: In TKA, this OFA-based OSA strategy improved early postoperative QoR-15 scores. However, the QoR-15 difference did not reach the minimal clinically important difference, so its clinical relevance remains uncertain.

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HumansArthroplasty, Replacement, KneePostoperative PainAgedAnalgesics, OpioidFemaleMaleMiddle AgedNerve BlockAnalgesia, Patient-ControlledPain MeasurementFemoral NerveRecovery of FunctionAnesthesia Recovery PeriodOxycodoneOpioid-free anesthesiaOpioid-sparing anesthesiaQuality of recoveryRandomized controlled trialTotal knee arthroplastyJournal ArticleRandomized Controlled TrialComparative Study

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Jingwang Liu, Jiaxin Liu, Peng Liu, Wenzhi Li, Mingjie Wang, Jinru Li, Shuhong Yang, Shuang Zhao, Xiuli Wang. 2026-08-22. Opioid-sparing anesthesia based on opioid-free principles for early recovery after total knee arthroplasty: A randomized controlled trial.. https://doi.org/10.1016/j.jclinane.2026.112307

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Journal Article; Randomized Controlled Trial; Comparative Study resourceAged subjectAnalgesia, Patient-Controlled subjectAnalgesics, Opioid subjectAnesthesia Recovery Period subjectComparative Study subjectFemale subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subjectNerve Block subjectPain Measurement subjectPostoperative Pain subjectRandomized controlled trials study

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