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Effects of opioid-free intraoperative anesthesia versus opioid-based anesthesia on postoperative immune function in elderly patients undergoing total knee arthroplasty: a single-center, prospective, randomized controlled trial
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DOI：10.1186/s12877-026-08081-7.png)
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Abstract
En 中文
Total knee arthroplasty (TKA) in elderly patients may involve postoperative immune suppression. This study compares intraoperative opioid-free anesthesia (OFA) and opioid-based anesthesia (OBA) effects on postoperative proportion of immune cells. The core pharmacological difference between groups lies in the intraoperative anesthetic regimen: the OBA group received sufentanil for induction and continuous remifentanil infusion for maintenance, while the OFA group replaced all intraoperative opioids with esketamine. Both groups received opioid-containing patient-controlled intravenous analgesia and rescue analgesia after surgery, and the opioid-free anesthesia protocol was only applied during the intraoperative phase. A single-center, prospective, randomized controlled trial of 60 patients (60–80 years) undergoing unilateral TKA. The opioid-free strategy was exclusively implemented during the intraoperative period, and both groups received identical opioid-inclusive postoperative analgesia. Patients were randomized into OFA (n = 30) and OBA (n = 30) groups. Primary outcome: change in natural killer (NK) cell proportion. Secondary outcomes: T-cell subsets (CD3⁺, CD4⁺, CD8⁺), B cells, dynamic/static visual analogue scale (VAS) scores, patient-controlled intravenous analgesia (PCIA) demands, Pittsburgh Sleep Quality Index (PSQI), hemodynamics, and adverse events. We conducted an intention-to-treat (ITT) analysis in 60 patients (30 in each group). Baseline demographics and preoperative immune indices showed no significant differences between the groups. Compared with the levels one day before the operation, the postoperative reduction in NK cell proportion was significantly smaller in the OFA group than in the OBA group (Δ = -5.51% ± 4.89% vs. Δ = -10.12% ± 5.39%; P < 0.001). The OFA group demonstrated superior early postoperative analgesia, with lower dynamic and static VAS scores at 4–48 h (P < 0.05), reduced PCIA demands at 24 h (5.8 ± 0.9 vs. 7.2 ± 1.1) and 48 h (6.1 ± 1.0 vs. 8.5 ± 1.3; P < 0.05), and better PSQI (7.50 ± 3.34 vs. 10.86 ± 4.01; P < 0.001). The OFA group had significantly lower intraoperative vasoactive agent consumption (atropine, norepinephrine, ephedrine) and 72-hour postoperative opioid consumption (all P < 0.05), and exhibited superior postoperative functional exercise capacity (active knee flexion angle and maximum walking distance) at 48 and 72 h postoperatively (all P < 0.05). No significant differences were observed between the groups in CD8⁺ T cell, B cell proportions, extubation time, length of hospital stay, rescue analgesia rate or postoperative nausea and vomiting (PONV) incidence (all P > 0.05). In elderly patients undergoing unilateral total knee arthroplasty, intraoperative esketamine-based opioid-free anesthesia was associated with a smaller decline in NK-cell proportion, superior early analgesia, and improved short-term sleep quality compared with opioid-based anesthesia. These findings are limited to the comparison of intraoperative strategies and cannot be extrapolated to full perioperative opioid-free management. Chinese clinical trial registry, ID: ChiCTR2300069836; Date: 27/03/2023.
Keywords:
Opioid-free intraoperative anesthesia
Postoperative Immune Function
Total Knee Arthroplasty
Elderly Patients
Esketamine
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