Low-dose ketamine affects immune responses in humans during the early postoperative period

Low-dose ketamine affects immune responses in humans during the early postoperative period
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DOI:
10.1093/bja/aem218
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发表时间:
2007-10-01
影响因子:
9.8
通讯作者:
Bessler, H.
Bessler, H.
中科院分区:
医学1区
文献类型:
--
作者:
Beilin, B.;Rusabrov, Y.;Bessler, H.

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背景麻醉和手术与免疫系统受损相关,表现为过度的促炎性免疫反应和细胞介导的免疫抑制,可能影响术后病程。增加麻醉剂能够减轻围手术期免疫功能的改变,可能会对患者的愈合产生有利的影响。我们评估了术前给予亚麻醉剂量的氯胺酮对有丝分裂原反应和外周血单核细胞(PBMC)产生白细胞介素(IL)-1 β、IL-2、IL-6和肿瘤坏死因子(TNF)-α的影响,以及接受腹部手术的患者的自然杀伤细胞毒性(NKCC)。17例择期腹部手术的患者在全麻诱导前5分钟静脉注射氯胺酮0.15 mg/kg。19名患者在麻醉诱导前5分钟接受了类似体积的等渗盐水。分别于术前、术后4、24、48、72 h采集外周血,检测外周血单个核细胞(PBMC)分泌IL-1 β、IL-2、IL-6、TNF-α的水平,并进行NKCC检测。术后4 h,氯胺酮组IL-6的产生明显低于对照组(P < 0.01)。IL-2的产生与术前样品相比没有变化。对照组术后4 h TNF-α分泌明显升高(P <0. 05)。在麻醉诱导前添加小剂量氯胺酮导致促炎细胞因子IL-6和TNF-α的分泌减弱,并使IL-2的产生保持在术前水平。这表明这种麻醉剂可能对预防术后早期免疫功能改变有价值。
Background. Anaesthesia and surgery are associated with impairment of the immune system expressed as an excessive proinflammatory immune response and suppression of cell-mediated immunity that may affect the course of the postoperative period. Addition of anaesthetic agents capable of attenuating the alterations in perioperative immune function may exert a favourable effect on patients' healing. We have assessed the effect of preoperative administration of a sub-anaesthetic dose of ketamine on the mitogen response and production of interleukin (IL)- 1 beta, IL-2, IL-6, and tumour necrosis factor (TNF)-alpha by peripheral blood mononuclear cells (PBMCs), as well as natural killer cell cytotoxicity (NKCC) in patients undergoing abdominal surgery.Methods. Seventeen patients admitted for elective abdominal surgery were given ketamine 0.15 mg kg(-l) i.v. 5 min before induction of general anaesthesia. Nineteen patients received a similar volume of isotonic saline 5 min before induction of the anaesthesia. PBMCs were isolated from venous blood before and 4, 24, 48, and 72 h after operation for IL-1 P, IL-2, IL-6, and TNF-alpha secretion, and NKCC assessment.Results. Four hours after operation, the cells from patients in the ketamine group showed a significantly suppressed production of IL-6 (P < 0.01) compared with controls. The production of IL-2 did not change from that of the preoperation samples. TNF-alpha secretion was significantly elevated in the control group 4 h after operation (P < 0.05).Conclusions. Addition of small doses of ketamine before induction of anaesthesia resulted in attenuation of secretion of the proinflammatory cytokines IL-6 and TNF-alpha, and in preservation of IL-2 production at its preoperative level. It is suggested that this anaesthetic may be of value in preventing immune function alterations in the early postoperative period.