Ketamine Does Not Change Natural Killer Cell Cytotoxicity in Patients Undergoing Cancer Surgery: Basic Experiment and Clinical Trial

Abstract

Background. The natural killer cell cytotoxicity (NKCC) suppressed by nociceptive stimuli, systemic inflammation, and drugs used during cancer surgery may be associated with poor outcomes. We investigated the potential modulation of ketamine on NKCC in vitro and in a clinical setting during cancer surgery. Subjects and Methods. The NK cell line KHYG1 was cultured for the in vitro experiments. The NK cells were treated with 3 and 10 μM ketamine (the ketamine groups) or without ketamine (the control) for 4, 24, and 48 h. The posttreatment NKCC was measured with a lactate dehydrogenase assay and compared among the treatment groups. For the clinical study, lung cancer patients ( $n=38$ ) and prostate cancer patients ( $n=60$ ) who underwent radical cancer surgeries at a teaching hospital were recruited. The patients received propofol and remifentanil superposed with or without ketamine (ketamine group, $n=47$ ; control group, $n=51$ ). The primary outcome was the difference in NKCC between these groups. Results. In the in vitro experiment, the cytotoxicity of NK cells was similar with or without ketamine at all of the incubation periods. The patients’ NKCC was also not significantly different between the patients who received ketamine and those who did not, at the baseline ( $36.6\pm 16.7$ % vs. $38.5\pm 15.4$ %, $p=0.56$ ) and at 24 h ( $25.6\pm 12.9$ % vs. $27.7\pm 13.5$ %, respectively, $p=0.49$ ). Conclusion. Ketamine does not change NKCC in vitro or in the clinical setting of patients who undergo cancer surgery. This trial is registered with UMIN000021231.