Brown Jeremiah R, Birkmeyer Nancy J O, O'Connor Gerald T
Center for the Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, NH, USA.
Circulation. 2007 Jun 5;115(22):2801-13. doi: 10.1161/CIRCULATIONAHA.106.671222. Epub 2007 May 28.
Since the 1980s, antifibrinolytic therapies have assisted surgical teams in reducing the amount of blood loss. To date, however, serious questions remain regarding the safety and effectiveness of these agents.
We conducted a meta-analysis to compare aprotinin, epsilon-aminocaproic acid, and tranexamic acid with placebo and head to head on 8 clinical outcomes from 138 trials. Published randomized controlled trial data were collected from OVID/PubMed. Outcomes included total blood loss, transfusion of packed red blood cells, reexploration, mortality, stroke, myocardial infarction, dialysis-dependent renal failure, and renal dysfunction (0.5-mg/dL increase in creatinine from baseline). All agents were effective in significantly reducing blood loss by 226 to 348 mL and the proportion of patients transfused with packed red blood cells over placebo. Only high-dose aprotinin reduced the rate of reexploration (relative risk, 0.49; 95% CI, 0.33 to 0.73). There were no significant risks or benefits for any agent for mortality, stroke, myocardial infarction, or renal failure. However, high-dose aprotinin significantly increased the risk of renal dysfunction (relative risk, 1.47; 95% CI, 1.12 to 1.94), 12.9% versus 8.4%. Compared head to head, high-dose aprotinin demonstrated significant reduction in total blood loss over epsilon-aminocaproic acid (-184 mL; 95% CI, -256 to -112) and tranexamic acid (-195 mL; 95% CI, -286 to -105). There were no significant differences among any agent when compared head to head on other outcomes.
All antifibrinolytic agents were effective in reducing blood loss and transfusion. There were no significant risks or benefits for mortality, stroke, myocardial infarction, or renal failure. However, high-dose aprotinin was associated with a statistically significant increased risk of renal dysfunction.
自20世纪80年代以来，抗纤溶疗法已帮助手术团队减少失血量。然而，迄今为止，这些药物的安全性和有效性仍存在严重问题。
我们进行了一项荟萃分析，将抑肽酶、氨甲环酸和氨甲苯酸与安慰剂进行比较，并就138项试验的8项临床结局进行直接对比。从OVID/ PubMed收集已发表的随机对照试验数据。结局包括总失血量、浓缩红细胞输注、再次手术探查、死亡率、中风、心肌梗死、依赖透析的肾衰竭和肾功能不全（肌酐水平较基线升高0.5mg/dL）。所有药物均能有效显著减少失血量226至348mL，且与安慰剂相比，输注浓缩红细胞的患者比例降低。只有高剂量抑肽酶降低了再次手术探查率（相对风险，0.49；95%可信区间，0.33至0.73）。对于死亡率、中风、心肌梗死或肾衰竭，任何药物均无显著风险或益处。然而，高剂量抑肽酶显著增加了肾功能不全的风险（相对风险，1.47；95%可信区间，1.12至1.94），分别为12.9%和8.4%。直接对比显示，高剂量抑肽酶与氨甲环酸相比，总失血量显著减少（-184mL；95%可信区间，-256至-112），与氨甲苯酸相比也显著减少（-195mL；95%可信区间，-286至-105）。在其他结局进行直接对比时，各药物之间无显著差异。
所有抗纤溶药物均能有效减少失血量和输血。对于死亡率、中风、心肌梗死或肾衰竭，无显著风险或益处。然而，高剂量抑肽酶与肾功能不全风险的统计学显著增加相关。
