Aprotinin

Aprotinin, a naturally occurring serine protease inhibitor, saves lives and decreases the risk of stroke and repeat surgery for massive bleeding^{1, 2, 3}.

The use of aprotinin did not significantly increase the risk of renal failure or the need for postoperative renal replacement despite an increase in the proportion of patients who had a doubling of serum creatinine levels. The adjudication of death did not identify renal failure as contributing to or causing death associated with aprotinin use. A Meta analysis by Brown and colleagues showed a nonsignificant relative risk of renal failure with high-dose aprotinin⁴.

Although aprotinin is potentially more effective than other active agents in controlling hemostasis, we noted only a possible trend suggesting that it decreased massive bleeding. Only repeat surgeries and important blood losses through chest tubes, one of the main indications for surgery, were potentially improved by the use of aprotinin. Aprotinin did not appear to prevent massive bleeding or save the life of patients who had massive bleeding.

The adverse effects on mortality associated with aprotinin may also have been present among healthier patients, those under the age of 65 years, and those without coexisting illnesses at the time of surgery.

Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin as compared with lysine analogues precludes its use in patients undergoing high-risk cardiac surgery⁵.

Reference:
1.Henry DA, Carless PA, Moxey AJ, et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev 2007;4:CD001886.
2.Levi M, Cromheecke ME, de Jonge E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 1999;354:1940-7.
3.Sedrakyan A, Treasure T, Elefteriades JA. Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials. J Thorac Cardiovasc Surg 2004;128:442-8.
4.Brown JR, Birkmeyer NJ, O’Connor GT. Meta-analysis comparing the effectiveness and adverse outcomes of antifibrinolytic agents in cardiac surgery. Circulation 2007;115:2801-13.
5.Dean A. Fergusson, Paul C. Hébert et al, A Comparison of Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery, N Engl J Med 2008; 358:2319-2331

抑肽酶是一种天然存在的丝氨酸蛋白酶抑制剂,可挽救生命并降低中风和因大量出血而重复手术的风险^{1, 2, 3}。

尽管血清肌酐水平加倍的患者比例增加,但抑肽酶的使用并未显着增加肾功能衰竭或术后肾脏置换需求的风险。死亡裁定并未将肾功能衰竭确定为促成或导致与抑肽酶使用相关的死亡。 Brown 及其同事的一项荟萃分析显示,大剂量抑肽酶⁴ 的肾衰竭相对风险不显着。

虽然抑肽酶在控制止血方面可能比其他活性药物更有效,但我们只注意到一个可能的趋势表明它可以减少大出血。只有重复手术和通过胸管大量失血（手术的主要适应症之一）才可能通过使用抑肽酶得到改善。抑肽酶似乎不能预防大出血或挽救大出血患者的生命。

抑肽酶对死亡率的不利影响也可能存在于更健康的患者、65 岁以下的患者以及手术时没有合并症的患者中。

尽管与赖氨酸类似物相比,抑肽酶可能会适度降低大出血的风险,但其强烈且一致的负死亡率趋势阻碍了其在接受高风险心脏手术的患者中的使用^5.