The Impact of Anesthesia on Immune Function
When the body’s protective barriers (such as the skin) are breached, the body responds by activating the innate immune system. Affected tissues and cells release chemical messengers to call innate immune cells to action. On the other hand, the adaptive immune system responds to infection, which can occur in the exposed wound, by recruiting T-cells and B-cells. Surgical trauma can simultaneously activate both innate and adaptive immune systems. During and immediately after surgery, a sharp increase in proinflammatory cytokines at the surgical site initiates healing. To maintain homeostasis, anti-inflammatory cytokines increase in number and control the proinflammatory response. Regulatory balance between proinflammatory and anti-inflammatory responses determines the patient’s prognosis, i.e. whether a patient develops postoperative complications such as sepsis, tumor recurrence, or multiple organ failure. Anesthesia may directly and indirectly influence this balance via sustained suppression of the immune response; this may predispose patients to sepsis or, in the case of cancer patients, tumor metastasis.[1]
Volatile anesthetics seem to suppress and impair immune function; they may be linked to tumor growth and to aggregation of neurodegenerative proteins.[2–3] For instance, sevoflurane decreases neutrophil count[4], inhibits neutrophil activation and adhesion[5], decreases macrophage levels[6], decreases cytokine release in macrophages and in natural killer cells[7], suppresses natural killer cell cytotoxicity[8], and increases microglial activation leading to cognitive decline[9]. Isoflurane shares many of these effects on the immune system, as well as additional immunosuppressive effects; overall effects of several volatile anesthetics (including desflurane, isoflurane, sevoflurane, and the discontinued halothane) on innate and adaptive immunity were compiled in a comprehensive 2016 review article by Stollings et al in 2016.[10]
Effects of various anesthetics may also be immune activating. One in vitro study showed that sevoflurane compensated for the immunosuppressive effect of nitrous oxide, namely decreased production of peripheral blood mononuclear cells; sevoflurane also compensates for thiopental’s effects, including decreased release of soluble interleukin-2 receptor and decreased cell proliferation.[11] Another example of potential benefits of sevoflurane is the increased release of cytokines such as interleukin-1?, interferon-?, and tumor necrosis factor-? in macrophages.[12] Because volatile anesthetics have complex effects on the immune response, both in vitro and in vivo models of research continue to address this new concern of the long-term impact of anesthetics in postoperative complications.
Indirect effects of anesthesia were also demonstrated, in prospective clinical research with differences in hormone production throughout the perioperative period. Compared to isoflurane, sevoflurane led to significantly lower glucocorticoid and cortisol levels in the blood at the end of the laparoscopic surgery; this was shown to coincide with lower levels of growth hormone and higher levels of prolactin. Overall, sevoflurane may generate a better stress response and thereby a better immune response than isoflurane.[13] More research on the impact of anesthesia on hormone levels will elucidate indirect impact on immune response.
Consideration of the impact of anesthesia on immune function is especially critical in oncologic surgeries, because the balance of immunosuppression and immune activation will have a direct impact on the regrowth or removal of cancerous cells.[14] For such surgeries, several clinical studies indicate that regional anesthesia may be a better option than general anesthesia, for select types of cancer.[15-20] While much more research is needed regarding the mechanisms of anesthetic effect on perioperative immune response, the profound impact is evident and should play a role in the customized course of anesthesia for all patients, particularly those that are immune-compromised, for the best possible outcome; anesthesiologists have a large role to play in regulating the immune response and optimizing the long-term outcome of patients after surgery.
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