Effects of esketamine combined with parecoxib sodium on early postoperative pain and inflammatory biomarkers after video-assisted thoracoscopic lung resection: a single-center, four-arm randomized controlled trial

<title>Abstract</title> <p> <bold>Background</bold> Postoperative pain and inflammation associated with one-lung ventilation may impair recovery after video-assisted thoracoscopic lung resection. We evaluated esketamine combined with parecoxib sodium for early analgesia and systemic postoperative inflammation. <bold>Methods</bold> In this single-center, four-arm randomized controlled trial in Chongqing, China, 100 patients undergoing video-assisted thoracoscopic lobectomy or segmentectomy were assigned 1:1:1:1 to parecoxib sodium (P group), esketamine (S group), both agents (PS group), or saline control (N group). The P group received intravenous parecoxib sodium 0.5 mg/kg 20 min before incision; the S group received an esketamine infusion of 0.25 mg/kg/h from anesthesia induction until 30 min before surgery ended; and the PS group received both interventions. The primary outcome was resting visual analog scale (VAS) score 30 min after extubation and at 6, 12, 24, and 48 h. Secondary outcomes included interleukin-6 (IL-6), C-reactive protein (CRP), hemodynamics, adverse events, and pulmonary complications. <bold>Results</bold> Of 100 randomized participants, 92 (23 per group) were included in the complete-case analysis. Exploratory overall comparisons showed between-group differences in resting VAS scores at 6 and 12 h (P &lt; 0.001 and P = 0.012), but not at 30 min, 24 h, or 48 h. The PS group had the lowest mean VAS scores at 6, 12, 24, and 48 h. IL-6 and CRP differed among groups on postoperative days 1, 3, and 6, with the lowest means in the PS group. Systolic and diastolic blood pressure and heart rate differed at incision, with the highest means in the S group. Adverse events and pulmonary complications were infrequent. <bold>Conclusions</bold> The combined regimen was associated with lower mean resting pain scores and inflammatory biomarker levels at several early postoperative time points. These exploratory findings support further evaluation of esketamine plus parecoxib sodium as a multimodal perioperative regimen. <bold>Trial registration:</bold> Chinese Clinical Trial Registry, ChiCTR2500095107. Registered 2 January 2025. </p>