The Effects of Low-Dose Esketamine Combined with Paravertebral Block on Postoperative Hyperalgesia and Enhanced Recovery in Non-Intubated Video-Assisted Thoracic Surgery: A Randomized Controlled Trial

Rongbo Zhang,1 Zhilin Luo,2 Hong Zhang,2 Qiansong Wang,1 Chengwen Luo,2 Jingrui He,3 Tianhu Wang2 1Department of Anesthesiology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing City, People’s Republic of China; 2Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing City, People’s Republic of China; 3Department of Ultrasound, Renji Hospital Affiliated to Chongqing University (Chongqing Fifth People’s Hospital), Chongqing City, People’s Republic of ChinaCorrespondence: Tianhu Wang, Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University, Yubei District, Chongqing City, 401120, People’s Republic of China, Tel +86-18302302533, Email [email protected]: Non-intubated video-assisted thoracic surgery (NIVATS) reduces airway trauma but may lead to postoperative hyperalgesia and opioid dependence, contradicting enhanced recovery after surgery (ERAS) principles. We hypothesized that combining low-dose esketamine with a paravertebral block (PVB) may mitigate hyperalgesia, decrease opioid requirements, and improve recovery quality in NIVATS.Patients and Methods: This prospective single-center, double-blind randomized controlled trial (RCT) enrolled 82 patients undergoing uniportal NIVATS. Patients were randomized into two groups: esketamine (0.25 mg/kg pre-induction + 0.15 mg/kg/h intraoperatively) and control. Both groups received ultrasound-guided T4 and T6 PVB (with 0.375% ropivacaine). The primary outcome was mechanical pain threshold (MPT; central/peripheral), quantified preoperatively and at 0.5– 48 h postoperatively using pressure algometry after laryngeal mask airway (LMA) removal. Secondary outcomes included quality of recovery-40 (QoR-40) scores, intraoperative sufentanil/norepinephrine use, postoperative rescue analgesia use, and other related complications.Results: Compared to controls, the esketamine group exhibited significantly higher MPT at 6 h postoperatively (central: 2.77 ± 0.80 vs 2.17 ± 0.59 kgf/cm², P < 0.001; and peripheral: 2.95 ± 0.89 vs 2.17 ± 0.62 kgf/cm², P < 0.001). It also showed markedly improved QoR-40 scores (POD1: 182.3 ± 6.0 vs 175.8 ± 7.2, P < 0.001; and POD3: 190.3 ± 2.9 vs 186.8 ± 3.6, P < 0.001). Compared to controls, the esketamine group also showed significantly lower intraoperative sufentanil consumption (median 5.0 vs 17.5 μg) and norepinephrine requirement (219.1 ± 124.7 vs 393.7 ± 182.3 μg), as well as postoperative rescue analgesia use (P < 0.05). Except for postoperative nausea and vomiting (PONV) incidence (P < 0.05), both groups had similar profiles in other adverse events.Conclusion: Low-dose esketamine combined with PVB attenuates postoperative hyperalgesia, reduces intraoperative opioid use by 71.4%, and enhances recovery in NIVATS, offering a clinically effective opioid-sparing strategy for ERAS protocols.Keywords: esketamine, non-intubated video-assisted thoracic surgery, paravertebral block, postoperative hyperalgesia, multimodal analgesia, ERAS