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已发表论文
艾氯胺酮作为罗哌卡因在膝关节神经和 IPACK 阻滞中的辅助用药用于全膝关节置换术：一项双盲随机试验
Authors Zhu X, Bao W, Wang L, Huang L, Wang Q, Pan L
Received 7 November 2025
Accepted for publication 9 December 2025
Published 12 December 2025 Volume 2025:19 Pages 11047—11056
DOI https://doi.org/10.2147/DDDT.S579720
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Anastasios Lymperopoulos
Xiaona Zhu,1 Wanli Bao,2 Lu Wang,3 Lvdan Huang,1 Quanguang Wang,1,* Linmin Pan1,*
1Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, The People’s Hospital of Wencheng, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Joint Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Linmin Pan, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86-150-6846-8153, Email panlinmin@wmu.edu.cn Quanguang Wang, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86-137-3693-5500, Email quanguangwang@wzhospital.cn
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.
Keywords: chronic postoperative pain, esketamine, peripheral nerve block, IPACK block, total knee arthroplasty
1Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, The People’s Hospital of Wencheng, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Joint Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Linmin Pan, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86-150-6846-8153, Email panlinmin@wmu.edu.cn Quanguang Wang, Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86-137-3693-5500, Email quanguangwang@wzhospital.cn
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.
Keywords: chronic postoperative pain, esketamine, peripheral nerve block, IPACK block, total knee arthroplasty