Brown Jeremiah R, Toler Andrew W J, Kramer Robert S, Landis R Clive
The Dartmouth Institute for Health Policy and Clinical Practice and Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
J Extra Corpor Technol. 2009 Jun;41(2):79-86.
It is important to define the extent, and any limitations, of potential anti-inflammatory regimens used in cardiac surgery to guide the rational combination of drugs to suppress the systemic inflammatory response. Aprotinin (Trasylol) is an anti-fibrinolytic agent with reported anti-inflammatory properties. In this study, we investigated the published data on aprotinin's effect on acute phase protein and cytokine levels in cardiac surgery patients. Randomized placebo-controlled trials of aprotinin published between 1985 and 2007, in adult cardiac surgery using cardiopulmonary bypass, reporting tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10 levels were included for review. Two independent reviewers graded each paper and collected information on inflammatory markers. RevMan 4.3 statistical software was used to calculate and plot the weighted mean difference between placebo and aprotinin groups. Thirteen studies met the review criteria. None of the inflammatory markers were reduced by high-dose aprotinin treatment. Low-dose aprotinin significantly reduced IL-10 levels after protamine administration (-41.3 pg/ mL; 95% CI: -59.5, -23.1), but this result was gone by the first post-operative day. These meta-analyses showed no significant effect of aprotinin on acute phase proteins or systemic cytokine markers of inflammation during clinical adult cardiac surgery using cardiopulmonary bypass. While recognizing that other host defense systems, such as coagulation and complement, contribute to the overall systemic inflammatory response, the evidence presented here does not support the clinical use of aprotinin as an anti-inflammatory agent on its own.
明确心脏手术中潜在抗炎方案的范围及任何局限性对于指导合理联合用药以抑制全身炎症反应至关重要。抑肽酶（Trasylol）是一种据报道具有抗炎特性的抗纤溶药物。在本研究中，我们调查了已发表的关于抑肽酶对心脏手术患者急性期蛋白和细胞因子水平影响的数据。纳入了1985年至2007年间发表的、在使用体外循环的成人心脏手术中进行的抑肽酶随机安慰剂对照试验，这些试验报告了肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、IL-8和IL-10水平以供综述。两名独立评审员对每篇论文进行评分并收集炎症标志物的信息。使用RevMan 4.3统计软件计算并绘制安慰剂组和抑肽酶组之间的加权平均差异。13项研究符合综述标准。高剂量抑肽酶治疗并未降低任何炎症标志物。低剂量抑肽酶在给予鱼精蛋白后显著降低了IL-10水平（-41.3 pg/mL；95%CI：-59.5，-23.1），但该结果在术后第一天就消失了。这些荟萃分析表明，在使用体外循环的临床成人心脏手术中，抑肽酶对急性期蛋白或全身炎症细胞因子标志物没有显著影响。虽然认识到其他宿主防御系统，如凝血和补体，也参与了整体全身炎症反应，但此处提供的证据并不支持单独将抑肽酶作为抗炎药物临床使用。
