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地氟烷和七氟烷麻醉对活体供肾移植患者调节性 T 细胞的影响:一项随机干预试验。

Effects of Desflurane and Sevoflurane anesthesia on regulatory T cells in patients undergoing living donor kidney transplantation: a randomized intervention trial.

机构信息

Department of Anesthesiology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.

Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand.

出版信息

BMC Anesthesiol. 2020 Aug 27;20(1):215. doi: 10.1186/s12871-020-01130-7.

Abstract

BACKGROUND

Volatile anesthetic agents used during surgery have immunomodulatory effects which could affect postoperative outcomes. Recognizing that regulatory T cells (Tregs) plays crucial roles in transplant tolerance and high peripheral blood Tregs associated with stable kidney graft function, knowing which volatile anesthetic agents can induce peripheral blood Tregs increment would have clinical implications. This study aimed to compare effects of desflurane and sevoflurane anesthesia on peripheral blood Tregs induction in patients undergoing living donor kidney transplantation.

METHODS

A prospective, randomized, double-blind trial in living donor kidney transplant recipients was conducted at a single center, tertiary-care, academic university hospital in Thailand during August 2015 - June 2017. Sixty-six patients were assessed for eligibility and 40 patients who fulfilled the study requirement were equally randomized and allocated to desflurane versus sevoflurane anesthesia during transplant surgery. The primary outcome included absolute changes of peripheral blood CD4CD25FoxP3Tregs which measured by flow cytometry and expressed as the percentage of the total population of CD4 T lymphocytes at pre-exposure (0-h) and post-exposure (2-h and 24-h) to anesthetic gas. P-value < 0.05 denoted statistical significance.

RESULTS

Demographic data were comparable between groups. No statistical difference of peripheral blood Tregs between desflurane and sevoflurane groups observed at the baseline pre-exposure (3.6 ± 0.4% vs. 3.1 ± 0.4%; p = 0.371) and 2-h post-exposure (3.0 ± 0.3% vs. 3.5 ± 0.4%; p = 0.319). At 24-h post-exposure, peripheral blood Tregs was significantly higher in desflurane group (5.8 ± 0.5% vs. 4.1 ± 0.3%; p = 0.008). Within group analysis showed patients receiving desflurane, but not sevoflurane, had 2.7% increase in peripheral blood Treg over 24-h period (p < 0.001).

CONCLUSION

This study provides the clinical trial-based evidence that desflurane induced peripheral blood Tregs increment after 24-h exposure, which could be beneficial in the context of kidney transplantation. Mechanisms of action and clinical advantages of desflurane anesthesia based on Treg immunomodulation should be investigated in the future.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT02559297 . Registered 22 September 2015 - retrospectively registered.

摘要

背景

手术中使用的挥发性麻醉剂具有免疫调节作用,可能影响术后结果。鉴于调节性 T 细胞(Tregs)在移植耐受和外周血高 Tregs 与稳定的肾脏移植物功能相关方面发挥着关键作用,了解哪种挥发性麻醉剂可以诱导外周血 Tregs 的增加将具有临床意义。本研究旨在比较地氟烷和七氟烷麻醉对活体供肾移植患者外周血 Tregs 诱导的影响。

方法

在泰国的一家单中心、三级保健、学术大学医院进行了一项前瞻性、随机、双盲试验,在 2015 年 8 月至 2017 年 6 月期间进行。对 66 名患者进行了资格评估,符合研究要求的 40 名患者被平均随机分配至地氟烷组或七氟烷组,在移植手术中接受麻醉。主要结局包括通过流式细胞术测量的外周血 CD4CD25FoxP3Tregs 的绝对变化,并以麻醉气体暴露前(0 小时)和暴露后(2 小时和 24 小时)的总 CD4 T 淋巴细胞的百分比表示。P 值<0.05 表示具有统计学意义。

结果

两组的人口统计学数据无差异。在基线暴露前(3.6±0.4%对 3.1±0.4%;p=0.371)和 2 小时暴露后(3.0±0.3%对 3.5±0.4%;p=0.319),地氟烷组和七氟烷组之间的外周血 Tregs 无统计学差异。在 24 小时暴露后,地氟烷组的外周血 Tregs 明显更高(5.8±0.5%对 4.1±0.3%;p=0.008)。组内分析显示,接受地氟烷的患者,而不是七氟烷,在 24 小时期间外周血 Treg 增加了 2.7%(p<0.001)。

结论

本研究提供了基于临床试验的证据,表明地氟烷在 24 小时暴露后诱导外周血 Tregs 增加,这可能有利于肾移植。未来应研究地氟烷麻醉基于 Treg 免疫调节的作用机制和临床优势。

试验注册

ClinicalTrials.gov,NCT02559297。2015 年 9 月 22 日注册-追溯注册。

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