The Intersection of Regional Anesthesia and Cancer Progression: A Theoretical Framework

The surgical stress and inflammatory response and volatile anesthetic agents have been shown to promote tumor metastasis in animal and in-vitro studies. Regional neuraxial anesthesia protects against these effects by decreasing the surgical stress and inflammatory response and associated changes in immune function in animals. However, evidence of a similar effect in humans remains equivocal due to the high variability and retrospective nature of clinical studies and difficulty in directly comparing regional versus general anesthesia in humans. We propose a theoretical framework to address the question of regional anesthesia as protective against metastasis. This theoretical construct views the immune system, circulating tumor cells, micrometastases, and inflammatory mediators as distinct populations in a highly connected system. In ecological theory, highly connected populations demonstrate more resilience to local perturbations but are prone to system-wide shifts compared with their poorly connected counterparts. Neuraxial anesthesia transforms the otherwise system-wide perturbations of the surgical stress and inflammatory response and volatile anesthesia into a comparatively local perturbation to which the system is more resilient. We propose this framework for experimental and mathematical models to help determine the impact of anesthetic choice on recurrence and metastasis and create therapeutic strategies to improve cancer outcomes after surgery.