Effects of perioperative esketamine infusion on chronic pain after video-assisted thoracoscopic lung resection: a multicentre, randomised, double-blind clinical trial

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• Picked for Anesthesiology and Pain Medicine (paper of the day, 30 October 2026): Randomized trial of perioperative esketamine preventing chronic postsurgical pain

Abstract

BACKGROUND: Chronic postsurgical pain after thoracoscopic surgery remains common. We investigated whether perioperative low-dose esketamine infusion would reduce chronic pain after video-assisted thoracoscopic lung resection. METHODS: In this multicentre, randomised controlled trial, 914 adults were randomly assigned (1:1) to receive either esketamine or normal saline. Esketamine was administered as a 0.1 mg kg-1 bolus at induction, followed by continuous intraoperative infusion (0.1 mg kg-1 h-1) and postoperative infusion (0.015 mg kg-1 h-1) for 48 h. The primary outcome was chronic pain at 3 months, defined as persistent pain with a numeric rating scale score ≥1 during coughing in the surgical region. Secondary outcomes included postoperative pain, supplemental analgesics use, recovery of bowel function, in-hospital adverse events, and esketamine-related side-effects. RESULTS: We analysed 873 patients (median age, 55 yr; 63% female). The incidence of 3 month chronic pain was lower in the esketamine group than in the control group (14.7% vs 21.2%; adjusted odds ratio, 0.62; 95% confidence interval, 0.43-0.90; P=0.013). A reduction was also observed when using a post hoc outcome definition of a numeric rating scale pain score ≥3 during coughing at 3 months (adjusted odds ratio, 0.39; 95% confidence interval, 0.19-0.84; P=0.015). Esketamine also reduced overall pain scores at rest and during coughing within the first 48 h, and decreased supplemental analgesic requirements within 48 h and 3 months. CONCLUSIONS: Perioperative low-dose esketamine infusion significantly reduced 3 month chronic pain after thoracoscopic lung resection without increasing adverse effects. CLINICAL TRIAL REGISTRATION: ChiCTR2000040012. TRIAL REGISTRATION: This trial was registered on the Chinese Clinical Trial Registry (Identifier: ChiCTR2000040012; principal investigator: Fu-hai Ji; dated November 18, 2020; https://www.chictr.org.cn/showprojEN.html?proj=62319).

Abstract as published, via PubMed.