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两剂大剂量促红细胞生成素术前应用不能减轻心脏手术的全身炎症反应。

Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery.

机构信息

Department of Cardiothoracic Anaesthesia, The Heart Centre, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

J Cardiothorac Vasc Anesth. 2009 Jun;23(3):316-23. doi: 10.1053/j.jvca.2008.08.018. Epub 2008 Oct 22.

Abstract

OBJECTIVES

Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB.

DESIGN AND SETTING

A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital.

PARTICIPANTS

Patients scheduled for coronary artery bypass graft surgery with CPB.

INTERVENTIONS

EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia.

MEASUREMENTS AND MAIN RESULTS

CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo.

CONCLUSIONS

Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.

摘要

目的

心脏手术和心肺转流(CPB)会引起炎症反应,从而导致组织损伤。实验研究表明,重组人促红细胞生成素(EPO)除了其促红细胞生成作用外,还可能在临床上用作抗炎药物。本研究检验了这样一个假设,即在 CPB 前短时间内给予 2 大剂量 EPO 可以改善 CPB 引起的全身炎症反应。

设计和设置

在一家单一的三级保健医院进行的前瞻性、双盲、安慰剂对照和随机研究。

参与者

计划进行 CPB 的冠状动脉旁路移植手术的患者。

干预措施

EPO(促红细胞生成素 alfa,500IU/kg 静脉内,n = 22)或安慰剂(n = 21)在术前 12 至 18 小时内给予,并在麻醉诱导时再次给予。

测量和主要结果

两组的 CPB 均大大增加了肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-1β受体拮抗剂、IL-6、IL-10 和 N 端脑钠肽前体(NT-proBNP)的血浆浓度。与安慰剂相比,EPO 在 CPB 后第 3 天增强了 TNF-α反应(p < 0.05),并在 CPB 后 2 小时增加了 NT-proBNP(p < 0.05)。此外,EPO 倾向于增强 CPB 诱导的 IL-1β受体拮抗剂增加(p = 0.057)。否则,EPO 与安慰剂相比对促炎和抗炎介质没有影响。

结论

CPB 前短时间内给予 2 大剂量 EPO 并不能减少围手术期炎症细胞因子的释放。相反,EPO 可能会增强 TNF-α和 NT-proBNP 反应。尽管长期的临床影响尚不清楚,但这些发现不支持在接受心脏手术的患者中使用 EPO 作为抗炎药物。

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