Effects of Perioperative Dexmedetomidine on Immunomodulation in Uterine Cancer Surgery: A Randomized, Controlled Trial

Abstract

Objective: Dexmedetomidine has sympatholytic, anti-inflammatory, and analgesic effects and may exert anti-tumor effect by acting on α2A adrenoreceptor. We investigated whether perioperative dexmedetomidine preserves immune function in patients undergoing uterine cancer surgery.

Methods: One hundred patients were randomly assigned to the control or dexmedetomidine groups (50 patients each). Dexmedetomidine was infused at rates of 0.4 μg/kg/h intraoperatively and 0.15 μg/kg/h during the first 24 h postoperatively. The primary outcome was natural killer (NK) cell activity, which was measured preoperatively and 1, 3, and 5 days postoperatively. The inflammatory response was measured by interleukin-6, interferon-γ, and neutrophil/lymphocyte ratio, and pain scores and opioid consumption were assessed. Cancer recurrence or metastasis and death were evaluated 2 years postoperatively.

Results: NK cell activity decreased postoperatively in both groups and changes over time were not different between groups (P=0.496). Interferon-γ increased postoperatively in the dexmedetomidine group, whereas it maintained at the baseline value in the control group. Change in interferon-γ differed significantly between groups (P=0.003). Changes in interleukin-6 and neutrophil-lymphocyte ratio were comparable between groups. Both pain score with activity during the first 1 h and opioid consumption during the first 1-24 h postoperatively were lower in the dexmedetomidine group. Rates of cancer recurrence/metastasis (16.3% vs. 8.7%, P=0.227) and death within 2 years postoperatively (6.7% vs. 2.2%, P=0.318) were not different between groups.

Conclusions: Perioperative dexmedetomidine had no favorable impacts on NK cell activity, inflammatory responses, or prognosis, whereas it increased interferon-γ and reduced early postoperative pain severity and opioid consumption in uterine cancer surgery patients.

Keywords: dexmedetomidine; immunity; interferon-γ; natural killer cell; uterine cancer.

Figure 1

Consort diagram.

Figure 2

The change of natural killer cell activity. The perioperative change in natural killer cell activity was similar between groups (P = 0.697). Data was analyzed using a linear mixed model after log-transformation for normality of distribution. NK cell, natural killer cell; Preop, preoperatively; POD, postoperative day; DEX group, dexmedetomidine group; ^* P < 0.05 compared to preoperatively.

Figure 3

The change of interferon-γ, interleukin-6, and neutrophil/lymphocyte ratio. Change in interferon-γ over time was significantly different between groups (P = 0.010), whereas changes in interleukin-6 and neutrophil/lymphocyte ratio were similar between two groups. Data was analyzed using a linear mixed model after log-transformation for normality of distribution. Preop, preoperatively; POD, postoperative day; DEX group, dexmedetomidine group; ^* P < 0.05 compared to preoperatively; ^† P < 0.05 compared to the Control group.