From the Departments of Anesthesiology and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York.
Anesth Analg. 2013 Oct;117(4):767-772. doi: 10.1213/ANE.0b013e3182a22258. Epub 2013 Sep 10.
Neonates are at high risk for bleeding complications after cardiovascular surgery. Activation of intravascular fibrinolysis is one of the principal effects of cardiopulmonary bypass that causes poor postoperative hemostasis. Antifibrinolytic medications such as tranexamic acid are often used as prophylaxis against fibrinolysis, but concentration/effect data to guide dosing are sparse for adults and have not been published for neonates. Higher concentrations of tranexamic acid than those necessary for inhibition of fibrinolysis may have adverse effects. Therefore, we investigated the concentration of tranexamic acid necessary to inhibit activated fibrinolysis in neonatal plasma.
We conducted an in vitro study using neonatal plasma derived from the placenta/cord units from 20 term, elective cesarean deliveries. Graded concentrations of tranexamic acid were added to aliquots of the pooled plasma before maximally activating fibrinolysis with high-dose tissue-type plasminogen activator. Thromboelastography was then performed with the primary outcome variable being lysis at 30 minutes. These procedures were repeated on pooled adult normal plasma and dilutions of neonatal plasma.
The minimum concentrations of tranexamic acid to completely prevent fibrinolysis were 6.54 μg/mL (95% confidence interval, 5.19-7.91) for neonatal plasma and 17.5 μg/mL (95% confidence interval, 14.59-20.41) for adult plasma. Neonatal plasma requires a significantly lower concentration than adult plasma (P < 0.0001, 2-sided Wald test).
Our data establish the minimal effective concentration of tranexamic acid necessary to completely prevent fibrinolysis in neonatal plasma in vitro. These data may be useful in designing a dosing scheme for tranexamic acid appropriate for neonates.
新生儿在心血管手术后有发生出血并发症的高风险。血管内纤维蛋白溶解的激活是体外循环的主要影响之一，导致术后止血不佳。抗纤维蛋白溶解药物如氨甲环酸常被用作纤维蛋白溶解的预防措施，但成人的浓度/效果数据指导剂量的信息很少，并且尚未在新生儿中发表。高于抑制纤维蛋白溶解所需的氨甲环酸浓度可能会产生不良影响。因此，我们研究了抑制新生儿血浆中激活的纤维蛋白溶解所需的氨甲环酸浓度。
我们进行了一项体外研究，使用来自 20 例择期剖宫产胎盘/脐带单位的新生儿血浆。将氨甲环酸的分级浓度加入到等分的混合血浆中，然后用大剂量组织型纤溶酶原激活剂最大程度地激活纤维蛋白溶解。然后用血栓弹性描记术进行检测，主要观察指标为 30 分钟时的溶解。在混合的成人正常血浆和新生儿血浆的稀释液上重复进行这些程序。
完全防止纤维蛋白溶解所需的氨甲环酸的最低浓度为新生儿血浆 6.54 μg/mL（95%置信区间，5.19-7.91）和成人血浆 17.5 μg/mL（95%置信区间，14.59-20.41）。新生儿血浆所需的浓度明显低于成人血浆（P < 0.0001，双侧 Wald 检验）。
我们的数据确定了在体外完全防止新生儿血浆中纤维蛋白溶解所需的氨甲环酸的最小有效浓度。这些数据可能有助于设计适合新生儿的氨甲环酸剂量方案。
