Combined General/Epidural Anesthesia vs. General Anesthesia on Postoperative Cytokines: A Review and Meta-Analysis

Background and Objectives: Local and systemic inflammation is common after surgery and is associated with morbidity and mortality. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery. The present study aimed to analyze inflammatory cytokines levels after surgery under combined epidural/general anesthesia (EA + GA) vs. general anesthesia (GA). Methods: We systematically searched PubMed, Central, EMBASE, CINAHL, Google Scholar, and Web of Science citation indexes for clinical studies (cancer and non-cancer surgery) comparing the two techniques. We carried out a meta-analysis to evaluate the postoperative plasma levels of cytokines, C-reactive protein (CRP), and cortisol levels. Results: The literature search was last updated on 2 January 2025. We identified a total of 21 studies which compared postoperative inflammatory mediators with EA plus GA compared to GA alone. EA plus GA was associated with significantly lower serum levels of IL-6, TNF-α, CRP, as well as cortisol and other pro-inflammatory cytokines. In cancer surgery, EA plus GA was also associated with lower postoperative cytokines. Conclusions: Our meta-analysis indicates that EA plus GA is associated with diminished postoperative inflammatory response. This offers an alternative explanation for the benefit of epidural analgesia on postoperative outcomes. Considering the link between postoperative inflammation and recurrence after cancer surgery, this is an area that warrants further research.