Immunomodulatory effects of total intravenous and balanced inhalation anesthesia in patients with bladder cancer undergoing elective radical cystectomy: preliminary results

Maria Sofra, Paola Cordiali Fei, Luana Fabrizi, Maria Elena Marcelli, Claudia Claroni, Michele Gallucci, Fabrizio Ensoli, Ester Forastiere, Maria Sofra, Paola Cordiali Fei, Luana Fabrizi, Maria Elena Marcelli, Claudia Claroni, Michele Gallucci, Fabrizio Ensoli, Ester Forastiere

Abstract

Background: Although surgery and anesthesia induce immunesuppression, remains largely unknown whether various anesthetic techniques have different immunosuppressive effects on cancer patients. Therefore, the aim of this study was to investigate the influence of total intravenous anesthesia with target-controlled infusion (TIVA-TCI) and balanced inhalation anesthesia (BAL) on the peri-operative levels of inflammatory cytokines and regulatory T cells (Tregs) in patients with bladder cancer undergoing surgery.

Methods: Twenty eight consecutive patients with bladder cancer who underwent radical cystectomy were prospectively randomized into two groups to receive TIVA-TCI (n = 14) or BAL (n = 14). Before the induction of anesthesia (T0), 6-8 hours (T1) post-surgery, and 5 days post-surgery (T2), Tregs and serum levels of interleukin -1beta (IL-1β), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin -2 (IL-2), interleukin -6 (IL-6), and interleukin -10 (IL-10) were measured.

Results: In the peri-operative period all cancer patients showed a marked and significant increase in IL-6. Moreover, TIVA-TCI patients also showed a higher increase in IFN-γ, whereas in BAL patients Tregs were reduced by approximately 30% during surgery. The incidence of infections, metastases, and death was similar in both groups.

Conclusions: The increase in the Th1 response in the TIVA-TCI group and the reduction in Tregs in the BAL group seem to balance the immunosuppressive effect induced by IL-6. Therefore TIVA-TCI and BAL can be both used in major surgery in patients with bladder cancer without worsening the outcome.

Figures

Figure 1
Figure 1
Changes in cytokine levels between T0 (before the induction of anesthesia) and T1 (6–8 hours post-surgery) and between T0 and T2 (5 days post-surgery) in all cases, in TIVA-TCI, and BAL. TIVA-TCI and BAL patients showed a marked and significant increase in IL-6 at T1 compared to values prior to surgery (T0) (p = 0.005), with an increase of about 50 times. These values were reduced at T2, but remained about 10 times higher than baseline values (p = 0.005). There were no significant differences between the TIVA-TCI and BAL groups. The TIVA-TCI group showed a significant increase in TNF-α levels between T2 and T0 compared to the BAL group (2.34 vs. 1.29 times, p = 0.001). At T1, differences were not statistically significant due to the high variability observed. Similarly, the increase in IFN-γ observed at T2 was significantly different in patients undergoing TIVA-TCI anesthesia compared to BAL. IFN-γ levels showed an increase of 2.26 times at T2 compared to T0 in the TIVA-TCI group and only 1.03 times in the BAL group (p = 0.002). The values of other cytokines remained constant during the three measurements in both groups.

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