Klein M, Keith P R, Dauben H P, Schulte H D, Beckmann H, Mayer G, Elert O, Gams E
Heinrich-Heine-University Duesseldorf, Department of Thoracic- and Cardiovascular Surgery, Germany.
Eur J Cardiothorac Surg. 1998 Oct;14(4):360-6. doi: 10.1016/s1010-7940(98)00192-4.
As Aspirin (ASA) has proven efficacy in preventing patients with CAD from complications related to cardiovascular diseases, most patients scheduled for CABG are treated with ASA therapy. Consequently, impaired hemostasis is a problem in the management of CABG patients. Clinical studies have shown that Aprotinin can reduce bleeding and the use of blood products by 50% in patients both with and without pre-operative ASA therapy. Concerning the combined effect of peri-operative low-dose ASA therapy and intra-operative high-dose Aprotinin therapy, the gathering of additional and prospective data seemed to be necessary.
We conducted a double-blind two-centre randomised three-arm study in patients with elective primary CABG surgery. Three groups have been tested, comprising 119 patients in total (group A: ASA + Aprotinin, group B: placebo + Aprotinin, group C: placebo + placebo) to investigate a possible reduction of bleeding in Aprotinin treated patients. For all patients, thromboxane levels were used to identify ASA or placebo treatment.
The post-operative blood loss is significantly reduced by 21% after Trasylol administration (B vs. C; P = 0.009). The unexpected result of this study has been that the pre-treatment with ASA led to a further reduction of 18% (A vs. C; P < 0.0001). The difference between the two Aprotinin groups (A and B) is significant (P = 0. 01) in favour of ASA pre-treatment. Myocardial infarction (MI) had been diagnosed at levels of 1.8% in total (2/113), 2.6% (1/38) in group B and 3.2% (1/31 ) in group C. An additional blinded evaluation of ECG, enzyme levels and clinical status revealed 'definite, probable and possible' MIs of 5% in group A, compared to 16% in group B and 13% in group C, thus providing no evidence for a higher risk of infarction by Aprotinin treatment. When comparing the ASA group to non-ASA pre-treatment, a strong trend towards a reduction in MI rate becomes obvious, from 15% to 5% in favour of the ASA pre-treatment (P = 0.08). Concerning other peri-operative complications, no statistical difference between the groups could be detected.
A reduction in post-operative blood loss in primary elective CABG surgery with intra-operative Aprotinin treatment could be confirmed. A low-dose ASA treatment combined with a high-dose aprotinin administration during surgery not only neutralized a potentially higher risk of bleeding, but did in fact reduce the post-operative blood loss. The protective effect of ASA on peri-operative MI has been evident through a reduction of MI rate in ASA treated patients.
由于阿司匹林（ASA）已被证明在预防冠心病患者发生心血管疾病相关并发症方面具有疗效，大多数计划进行冠状动脉旁路移植术（CABG）的患者都接受ASA治疗。因此，止血功能受损是CABG患者管理中的一个问题。临床研究表明，抑肽酶可使接受和未接受术前ASA治疗的患者的出血量和血制品使用量减少50%。关于围手术期低剂量ASA治疗与术中高剂量抑肽酶治疗的联合效果，似乎有必要收集更多前瞻性数据。
我们对择期进行初次CABG手术的患者进行了一项双盲、两中心、随机三臂研究。共测试了三组，总共119例患者（A组：ASA + 抑肽酶，B组：安慰剂 + 抑肽酶，C组：安慰剂 + 安慰剂），以研究抑肽酶治疗患者是否可能减少出血。对于所有患者，使用血栓素水平来确定是接受了ASA治疗还是安慰剂治疗。
给予抑肽酶（Trasylol）后，术后失血量显著减少21%（B组与C组比较；P = 0.009）。本研究的意外结果是，ASA预处理导致失血量进一步减少18%（A组与C组比较；P < 0.0001）。两个抑肽酶组（A组和B组）之间的差异显著（P = 0.01），有利于ASA预处理。总共1.8%（2/113）的患者被诊断为心肌梗死（MI），B组为2.6%（1/38），C组为3.2%（1/31）。对心电图、酶水平和临床状况进行的另一项盲法评估显示，A组“明确、可能和疑似”MI的发生率为5%，B组为16%，C组为13%，因此没有证据表明抑肽酶治疗会增加梗死风险。将ASA组与未进行ASA预处理的组进行比较时，MI发生率有明显降低的强烈趋势（从15%降至5%），有利于ASA预处理（P = 0.08）。关于其他围手术期并发症，各组之间未检测到统计学差异。
术中使用抑肽酶治疗可减少初次择期CABG手术的术后失血量这一点可以得到证实。手术期间低剂量ASA治疗与高剂量抑肽酶联合使用不仅抵消了可能更高的出血风险，而且实际上减少了术后失血量。通过降低接受ASA治疗患者的MI发生率，ASA对围手术期MI的保护作用已很明显。
