Comparative influence of opioid-free versus opioid-containing anesthetic techniques upon Th1/Th2 balance during laparoscopic colorectal cancer procedures: a randomized controlled trial

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Abstract Background Surgical resection is central to colorectal cancer management, but surgery and anesthesia can induce perioperative immunosuppression. Opioids, a mainstay of perioperative analgesia, may impair cellular immunity, including disruption of Th1/Th2 immune equilibrium. This randomized controlled trial evaluated whether opioid-free anesthesia (OFA) better preserves perioperative immune function than opioid-based anesthesia. Methods Sixty patients scheduled for elective laparoscopic colorectal cancer resection were randomly allocated to OFA (dexmedetomidine, esketamine, lidocaine) or opioid-based anesthesia (sufentanil, remifentanil). Peripheral blood was sampled before induction and on postoperative days 1 and 5 to measure Th1/Th2 ratio, CD4⁺/CD8⁺ ratio and natural killer (NK)-cell counts. Serum cortisol, measures of postoperative pain and complications, including postoperative nausea and vomiting (PONV), were documented. Results On postoperative day 5, the Th1/Th2 ratio was markedly reduced in patients given OFA relative to the control (C) group (1.14 ± 0.40 vs. 1.57 ± 0.89, P = 0.017); in the C group it had returned to baseline, whereas it remained suppressed with OFA. CD4⁺/CD8⁺ ratios and NK-cell counts showed no between-group differences at any point. Cortisol levels at the end of surgery and Numeric Rating Scale pain scores on day 1 were significantly lower with opioid-based anesthesia, while PONV incidence was lower with OFA. Conclusions In laparoscopic colorectal cancer surgery, the OFA regimen used in this trial was associated with sustained postoperative reduction of the Th1/Th2 ratio compared with opioid-based anesthesia. Although OFA reduced PONV, its potential to prolong Th1/Th2 suppression warrants caution when selecting anesthetic strategies for these patients. Trial registration This trial was retrospectively registered with the Chinese Clinical Trial Registry under ChiCTR2500101735 (registered April 29, 2025).