Cancer Mortality Affected by the Choice of Anesthetic Drugs?

Purpose and aims By means of record-linkage, information from two registers will be merged to retrospectively examine possible associations between survival from breast-, colorectal-, or skin cancer with the choice of hypnotic used during surgical removal of the cancer.

We hypothesize that: the one- and five-year survival rate after radical breast-, colorectal- or skin cancer surgery in general anesthesia is significantly higher in patients given the intravenously administered hypnotic propofol compared with the survival in patients exposed to the inhalational hypnotic sevoflurane.

The hypothesis is based on: 1) The knowledge about the opposite effects on the immune system from the two different anesthetics and from their different genotoxic potentials 2) The well-established associations between the state of the immune system and cancer growth, and DNA damage and cancer development, with potential influences on survival.

Survey of the field Rationale and current state of knowledge A) Immuno-modulation Converging evidence from animal studies and studies of human cell-lines indicate that different anesthetics have opposite effects on the immune system. Commonly used inhalational hypnotics are in this context pro-inflammatory, whereas the intravenously administered hypnotic agent propofol is anti-inflammatory and also anti-oxidative. A few clinical studies have indicated similar effects in patients, and a recent review has suggested that "tailoring an anesthetic plan to patient's needs will become increasingly critical, and immunology should help in this pursuit".

More specifically, previous studies have investigated the immunological effects of different anesthetics on monocytes, macrophages, natural killer cells, t-cytotoxic cells, and t-helper cells. By affecting t-helper cells anesthetics indirectly affects the production of anti-inflammatory mediators, such as interleukin-4 and -10. Anesthetics also affect the production of pro-inflammatory cytokines, such as tumor necrosis factor alpha, and interleukin-1 and -6. Moreover, the effects could be indirect by blocking or non-blocking of the surgical stress response via the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Thus, stress hormones, such as catecholamines and cortisol, mediates inhibitory effects on immune functions. In a highly complex way, the neuroendocrine system together with both pro-inflammatory- and anti-inflammatory cytokines augments their immuno-suppressive effects. Taken together, results from previous research support that inhalational hypnotics are immuno-suppressive in mice as well as in humans.