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Esketamine as an Adjuvant to Ropivacaine in Genicular Nerve and IPACK Blocks for Total Knee Arthroplasty: A Double-Blind Randomized Trial

Zhu X, Bao W, Wang L, Huang L, Wang Q, Pan L

Drug design, development and therapy, 2025

367 participants

Abstract

Purpose: Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) affects up to 44% of patients and markedly impairs recovery and quality of life. Although regional anesthesia is integral to multimodal analgesia, its preventive effect on CPSP remains limited. Esketamine, a potent N-methyl-D-aspartate receptor antagonist with analgesic and neuroprotective properties, may enhance local anesthetic efficacy and reduce the development of chronic pain.

Patients and methods: In this prospective, randomized, double-blind trial, 367 patients undergoing unilateral TKA under general anesthesia with peripheral nerve blocks were allocated to three groups: CTRL (normal saline), ROP (0.5% ropivacaine), and ESK (0.5% ropivacaine plus esketamine 0.2 mg/kg) for genicular nerve and IPACK blocks. The primary outcome was the incidence of CPSP (Numerical Rating Scale ≥ 4) at 6 months. Secondary outcomes included opioid consumption, NRS pain scores, Timed Up and Go (TUG) test, walking distance, Quality of Recovery-15 (QoR-15) scores, and adverse events.

Results: At 6 months, the incidence of CPSP was significantly lower in the ESK group (4.9%) than in the ROP (17.9%) and CTRL (27.0%) groups. Esketamine significantly reduced overall pain burden (AUC = 559.3 ± 59.0 vs 641.9 ± 55.8 and 679.2 ± 58.5; P P < 0.001). Functional recovery improved, with shorter TUG times, longer walking distance, and higher QoR-15 scores. No serious adverse events or psychomimetic reactions were reported.…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 367 participants or records.

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