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.

Abstract

<h4>Purpose</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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, <i>P</i> < 0.001; and peripheral: 2.95 ± 0.89 vs 2.17 ± 0.62 kgf/cm², <i>P</i> < 0.001). It also showed markedly improved QoR-40 scores (POD1: 182.3 ± 6.0 vs 175.8 ± 7.2, <i>P</i> < 0.001; and POD3: 190.3 ± 2.9 vs 186.8 ± 3.6, <i>P</i> < 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 (<i>P</i> < 0.05). Except for postoperative nausea and vomiting (PONV) incidence (<i>P</i> < 0.05), both groups had similar profiles in other adverse events.<h4>Conclusion</h4>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.

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