The immunomodulatory effect of ketamine in colorectal cancer surgery: a randomized-controlled trial

Ketamine's inhibitory action on the N-methyl-D-aspartate receptor and anti-inflammatory effects may provide beneficial immunomodulation in cancer surgery. We investigated the effect of subanesthetic-dose ketamine as an adjunct to desflurane anesthesia on natural killer (NK) cell activity and inflammation in patients undergoing colorectal cancer surgery.

A total of 100 patients were randomly assigned to a control or ketamine group. The ketamine group received a bolus of 0.25 mg·kg^-1 ketamine five minutes before the start of surgery, followed by an infusion 0.05 mg·kg^-1·hr^-1 until the end of surgery; the control group received a similar amount of normal saline. We measured NK cell activity and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) before surgery and one, 24, and 48 hr after surgery. C-reactive protein (CRP) was measured before surgery and one, three, and five days after surgery. Carcinoembryonic antigen and cancer recurrence/metastasis were assessed two years after surgery.

The NK cell activity was significantly decreased after surgery in both groups, but the change was not different between groups in the linear mixed model analysis (P = 0.47). Changes in IL-6, TNF-α, CRP, and carcinoembryonic antigen levels were not different between groups (P = 0.27, 0.69, 0.99, and 0.97, respectively). Cancer recurrence within 2 years after surgery was similar between groups (10% vs 8%, P = 0.62).

Intraoperative low-dose ketamine administration did not convey any favourable impacts on overall postoperative NK cell activity, inflammatory responses, and prognosis in colorectal cancer surgery patients.

www.clinicaltrial.gov (NCT03273231); registered 6 September 2017.