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

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 < 0.0001). It also lowered 24-hour opioid consumption, with patients in the ESK group requiring less morphine equivalent (26.8 ± 11.5 mg) compared with the ROP (29.7 ± 11.8 mg) and CTRL (34.8 ± 11.9 mg) groups (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.

CONCLUSION

Esketamine as an adjuvant to ropivacaine in genicular and IPACK blocks significantly reduced CPSP incidence and improved early functional recovery after TKA without increasing adverse effects. Perineural esketamine may represent a safe and effective strategy to prevent pain chronification.