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

Br J Anaesth. 2026 Oct 28:S0007-0912(26)00693-8. doi: 10.1016/j.bja.2026.08.039. Online ahead of print.

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).

PMID:42951789 | DOI:10.1016/j.bja.2026.08.039