A Testable Hypothesis That May Explain the Morbidity and Mortality Caused by Surgical Stress

To the Editor: In response to the controversy generated by the report of Monk et al. (1), I propose a testable hypothesis to explain their observation that anesthetic technique affects the distant outcome of surgery. Surgical stress increases autonomic activity that increases Factor VIII activity and half-life and simultaneously exposes tissue factor to circulating Factor VII (2). These phenomena may synergistically activate thrombin-generating mechanisms of coagulation (3) and capillary hemostasis (4), whose effects may persist long after surgery (5). Thrombin increases may explain inflammation, insoluble fibrin production, metabolic elevation, cell proliferation, and many other phenomena. Capillary hemostasis may interfere with tissue perfusion and oxygenation (6,7), and thrombin increases may promote malignancy. These effects may largely explain both the immediate and distant pathologies of surgical stress (8,9). Such harmful effects may be mitigated by treatments that inhibit tissue factor (10) and/or anesthetic strategies that reduce surgical stress, such as opioid-based general anesthesia (11–13) or combined epidural-general anesthesia (14–16). These anesthetic strategies may better prevent harmful autonomic activation and capillary-level increases in systemic vascular resistance than those that rely primarily on inhaled anesthetics that depress Bispectral Index scores and cardiac output at higher concentrations (17). Lewis S. Coleman, MD Bakersfield, CA [email protected]