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氯胺酮作为辅助药物用于微创根治性前列腺切除术患者全静脉麻醉时的免疫调节作用:一项随机试验。

Immunomodulation by ketamine as an adjunct to total intravenous anesthesia in patients undergoing minimally invasive radical prostatectomy: A randomized pilot trial.

作者信息

Kawaguchi Jun, Ota Daichi, Niwa Hidetomo, Sugo Yuki, Kushikata Tetsuya, Hirota Kazuyoshi

机构信息

Department of Anesthesiology, Hirosaki University Hospital, Hirosaki, Aomori 036-8563, Japan.

Department of Anesthesiology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan.

出版信息

Mol Clin Oncol. 2020 Aug;13(2):203-208. doi: 10.3892/mco.2020.2060. Epub 2020 Jun 3.

Abstract

Post-surgery immunomodulation, including reduced natural killer cell cytotoxicity (NKCC), is recognized as a predictor of poor outcomes in patients following cancer surgery. The present study investigated direct immunomodulation via ketamine as an anesthetic adjuvant in patients undergoing cancer surgery. The present non-double blinded randomized trial was conducted at Hirosaki University Hospital with 60 patients who underwent minimally invasive robotic radical prostatectomy to minimize the immunomodulation due to surgical stress. Patients received total intravenous anesthesia using propofol and remifentanil, with ketamine as an anesthetic adjuvant (the ketamine group) or without ketamine (the control group). The primary outcome was the difference in NKCC between these groups. The secondary outcomes were the differences in neutrophil-lymphocyte ratio (NLR) and levels of interleukin (IL)-6, IL-1β, IL-10 and tumor necrosis factor-alpha (TNF-α). NKCC and cytokines were measured before anesthesia (baseline) and at 6 and 24 h after baseline measurements were recorded. NLR was determined on the last day before admission and at 48 h post-baseline. NKCC values were similar in each group at 6 h when compared with respective baseline results (baseline control, 36.9±15.6%; 6 h control, 38.3±13.4%; baseline ketamine, 36.1±17.0%; 6 h ketamine, 36.6±16.4%) but significantly decreased at 24 h (control, 26.5±12.2%; ketamine, 24.1±12.7%; P<0.001). There were no significant differences in NKCC between the ketamine and control groups (P=0.64) at any of the assessed time points. NLR, IL-1β, IL-10 and TNF-α levels were also similar between two groups. In contrast, IL-6 at 24 h was significantly lower in the ketamine group compared with the control group (mean difference, -7.3 pg ml; 95% confidence interval, -14.4 to -0.2; P=0.04). Ketamine as an anesthetic adjuvant did not provide direct immunomodulation in patients who underwent cancer surgery.

摘要

术后免疫调节,包括自然杀伤细胞细胞毒性(NKCC)降低,被认为是癌症手术后患者预后不良的一个预测指标。本研究调查了氯胺酮作为麻醉辅助剂对接受癌症手术患者的直接免疫调节作用。本非双盲随机试验在弘前大学医院进行,60例患者接受了微创机器人根治性前列腺切除术,以尽量减少手术应激引起的免疫调节。患者接受丙泊酚和瑞芬太尼全静脉麻醉,一组使用氯胺酮作为麻醉辅助剂(氯胺酮组),另一组不使用氯胺酮(对照组)。主要结局是两组之间NKCC的差异。次要结局是中性粒细胞与淋巴细胞比率(NLR)以及白细胞介素(IL)-6、IL-1β、IL-10和肿瘤坏死因子-α(TNF-α)水平的差异。在麻醉前(基线)以及记录基线测量值后的6小时和24小时测量NKCC和细胞因子。在入院前最后一天和基线后48小时测定NLR。与各自的基线结果相比,每组在6小时时的NKCC值相似(基线对照组,36.9±15.6%;6小时对照组,38.3±13.4%;基线氯胺酮组,36.1±17.0%;6小时氯胺酮组,36.6±16.4%),但在24小时时显著降低(对照组,26.5±12.2%;氯胺酮组,24.1±12.7%;P<0.001)。在任何评估时间点,氯胺酮组和对照组之间的NKCC均无显著差异(P=0.64)。两组之间的NLR、IL-1β、IL-10和TNF-α水平也相似。相比之下,氯胺酮组在24小时时的IL-6水平显著低于对照组(平均差异,-7.3 pg/ml;95%置信区间,-14.4至-0.2;P=0.04)。氯胺酮作为麻醉辅助剂对接受癌症手术的患者没有提供直接的免疫调节作用。

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