Effect of Intraoperative Subanesthetic-Dose Esketamine on Postoperative Hydromorphone Consumption After Total Hip Arthroplasty: A Randomized Double-Blind Placebo-Controlled Trial

Background: This randomized, double-blind, placebo-controlled trial evaluated whether intraoperative subanesthetic-dose esketamine reduces postoperative opioid consumption and improves early recovery outcomes after total hip arthroplasty (THA). Methods: A total of 128 patients was randomized to receive esketamine (Group E, n = 64) or saline (Group C, n = 64). Group E received an intravenous esketamine bolus of 0.25 mg/kg 5 minutes before skin incision, followed by a 0.25 mg/kg/h infusion until skin closure. Group C received an equivalent volume of normal saline using the same regimen. Postoperative analgesia was provided by patient-controlled intravenous analgesia with hydromorphone. The primary outcome was the cumulative hydromorphone consumption during the first 24 h after surgery. Secondary outcomes included 48-h hydromorphone consumption, Numeric Rating Scale (NRS) pain scores, quality of recovery (QoR-15), Athens Insomnia Scale (AIS), mood, and adverse events. Postoperative sleep disturbance (PSD) was assessed as an exploratory outcome. Results: The first 24-h hydromorphone consumption was significantly lower in Group E than in Group C (2.24 [2.08– 2.51] vs 3.20 [2.88– 3.40] mg, P < 0.001). Cumulative hydromorphone consumption over the first 48 h was also lower in Group E (4.40 [4.16– 4.82] vs 5.92 [5.30– 6.23] mg, P < 0.001). Group E had lower NRS scores at 6 and 24 h. On postoperative day 1, Group E exhibited higher QoR-15 scores and lower AIS scores ( P < 0.05), and the incidence of PSD was significantly lower in Group E than in Group C (26.6% vs 54.7%, P = 0.001). Adverse event rates did not differ significantly between groups ( P > 0.05). Conclusion: Intraoperative subanesthetic-dose esketamine reduced the first 24-h hydromorphone consumption after THA. Findings for the secondary outcomes are exploratory and require confirmation in future studies. Trial Registration: ChiCTR2600116506. Keywords: esketamine, total hip arthroplasty, opioid consumption, postoperative recovery, sleep quality