Effect of High-Dose Remifentanil Combined With Propofol on Perioperative Immune-Related Biomarkers in Patients Undergoing Radical Lung Cancer Surgery: A Randomized Trial

Background: Lung cancer surgery is associated with perioperative immune suppression and inflammatory responses, which may influence postoperative recovery and oncological outcomes. The immunomodulatory effects of different doses of remifentanil remain unclear. This study aimed to investigate the effects of high-dose remifentanil combined with propofol on perioperative immune-related biomarkers in patients undergoing radical lung cancer surgery.Methods: A total of 120 patients were assessed for eligibility; 12 were excluded before randomization; 108 were randomly assigned to three remifentanil groups (target plasma concentrations: 4, 8, and 16 ng/mL) and included in the analysis. Baseline characteristics, intraoperative variables, postoperative pain, recovery outcomes, and immune-inflammatory parameters were systematically compared among the three groups. Immune indices were dynamically assessed at multiple perioperative time points, and generalized estimating equations were used for repeated-measures analyses with appropriate corrections for multiple comparisons.Results: The three groups were comparable in baseline characteristics, surgical duration, anesthetic duration, and most intraoperative parameters (p > 0.05). Compared with the low-dose group, the high-dose group showed significantly increased natural killer (NK) cell counts at 24 and 72 h postoperatively (p < 0.05). In addition, the high-dose group exhibited significantly reduced levels of several inflammatory cytokines, including interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), at selected postoperative time points (p < 0.05); however, these differences were time-dependent and not consistently observed across all measurements. Postoperative pain scores at 4 and 48 h were significantly lower in the high-dose group compared with the low-dose group (p < 0.05). No significant differences were observed among groups in recovery quality or the incidence of postoperative nausea and vomiting (PONV) (p > 0.05). No serious adverse events occurred.Conclusion: High-dose remifentanil (16 ng/mL) combined with propofol was associated with changes in selected immune and inflammatory biomarkers at some time points. VAS scores were lower at 4 and 48 h in the high-dose group. No serious adverse events were observed; however, the high-dose group had a greater vasopressor requirement. These findings are exploratory and hypothesis-generating and require further validation.Clinical Trial Registry: Chinese Clinical Trial Registry (ChiCTR2300077233).