Impact of opioid-free general anesthesia with locoregional blocks during breast cancer surgery on systemic inflammatory response: results from a randomized controlled trial

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BACKGROUND: For breast cancer patients with localized disease, surgery remains a cornerstone of treatment. Anesthesia during surgery is essential for pain management and influences patient recovery. Opioid-free general anesthesia with locoregional blocks (OfGA), as an alternative to traditional opioid-based general anesthesia (GA), may improve patient outcomes. METHODS: We set up a randomized trial to compare the impact of different anesthetic approaches on post surgical inflammation in breast cancer patients undergoing quadrantectomy. Patients were randomized to receive GA (n=34) or OfGA (n=34). Blood samples were collected pre-surgery and 1 hour and 24 hours post-surgery. As primary endpoint, neutrophil-to-lymphocyte ratio (NLR) was calculated. As secondary endpoints we collected data on side effects, pain management, and circulating inflammatory cytokines. RESULTS: Patients of the GA arm displayed significantly increased NLR, both at 1 (median change +0.13, IQR 0.01 to 0.62, p<0.0001) and 24 (median change +0.64, IQR 0.28 to 1.03, p<0.0001) hours post-surgery, compared with baseline. On the contrary, the OfGA arm displayed stable or minimally increased NLR (median change -0.08, IQR -0.21 to 0.17, p=ns, at 1 hour; +0.11, IQR -0.11 to 0.36, p=ns, at 24 hours post-surgery). Circulating inflammatory cytokines aligned with NLR data, showing significant increases in key inflammatory factors in samples from the GA arm compared with the OfGA arm. Pain management was similar in both arms, but OfGA was better tolerated and elicited fewer side effects. CONCLUSIONS: In breast cancer surgery, opioid-free general anesthesia combined with locoregional blocks was associated with a reduced postoperative inflammatory response compared with conventional opioid-based general anesthesia, without compromising pain control. Further research is needed to determine whether these biological effects translate into meaningful clinical outcomes. TRIAL REGISTRATION NUMBER: NCT04172220.

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