Abstract：
The use of allogeneic blood products to restore hemostasis during pediatric cardiac surgery is associated with major risks. Consequently, there has been a growing interest in new patient blood management strategies, such as those based on the use of fibrinogen concentrate (FC). Accumulating evidence has shown FC supplementation to be safe and effective. Nevertheless, no guidelines are available on using FC in the pediatric setting, and few objective evaluations have been provided in clinical practice. The endpoint of this monocenter retrospective study was the hemostatic effect of additional FC in infants undergoing complex cardiac surgery with cardiopulmonary bypass to manage persistent clinically relevant bleeding. After weaning from cardiopulmonary bypass and after protamine administration, patients were transfused with conventional allogeneic products such as packed red blood cells, fresh frozen plasma (FFP), and platelets. In the case of redo surgery, according to the institutional protocol, patients also received tranexamic acid. In case of clinically persistent relevant bleeding, according to the anesthesiologist\'s judgment and thromboelastography, patients received FC supplementation (group with FC) or further FFP transfusions without receiving FC supplementation (group without FC). The primary endpoint was the hemostatic effects of FC. Secondary endpoints were the functional hypofibrinogenemia threshold value (expressed as maximum amplitude fibrinogen, MA-Fib) and postoperative MA-Fib, fibrinogenemia, intraoperative transfusions, and adverse events (AEs). In total, 139 patients who underwent cardiac surgery with CPB and aged less than 2 years were enrolled: 70 patients received allogeneic blood products and FC supplementation (group FC); 69 patients received allogeneic products without FC supplementation (group without FC). Patients that received FC supplementation were characterized by a significantly longer time of extracorporeal circulation (p < 0.001) and aortic cross-clamping (p < 0.001), a significantly lower minimum temperature (p = 0.011), increased use of concentrated prothrombin complex (p = 0.016) and tranexamic acid (p = 0.010), and a significantly higher amount of packed red blood cells, platelets (p < 0.001) and fresh frozen plasma (p = 0.03). Postoperative bleeding and severe bleeding were not statistically different between patients treated with FC and those not treated with FC supplementation (p = 0.786 and p = 0.695, respectively); after adjustment, a trend toward reduced bleeding can be observed with FC (p = 0.064). Overall, 88% of patients with severe bleeding had MA-Fib < 10 mm; a moderate association between severe bleeding and MA-Fib (odds ratio 1.7, 95% CI 0.5-6.5, p = 0.425) was found. Increased MA-Fib and postoperative fibrinogen were higher in the FC group (p = 0.003 and p < 0.001, respectively) than in FFP. AEs in the FC group were comparable to those observed in less complicated surgeries. Our results suggest a potential role of FC in complex surgery in maintaining postoperative bleeding at a level comparable to less complicated surgical procedures and favoring the increase in postoperative MA-Fib and fibrinogen.
摘要：
在小儿心脏手术期间使用同种异体血液制品恢复止血与主要风险相关。因此,人们对新的患者血液管理策略越来越感兴趣，例如基于使用纤维蛋白原浓缩物(FC)的那些。越来越多的证据表明补充FC是安全有效的。然而，没有关于在儿科环境中使用FC的指南，在临床实践中很少提供客观评价。这项单中心回顾性研究的终点是在接受体外循环复杂心脏手术以管理持续的临床相关出血的婴儿中额外的FC的止血效果。体外循环断奶后和鱼精蛋白给药后，患者被输入常规的同种异体产品，如浓缩红细胞，新鲜冷冻血浆（FFP），和血小板。在重做手术的情况下，根据机构协议，患者还接受了氨甲环酸治疗.在临床上持续相关出血的情况下，根据麻醉师的判断和血栓弹力图,患者接受FC补充(有FC组)或未接受FC补充的进一步FFP输血(无FC组).主要终点是FC的止血作用。次要终点是功能性低纤维蛋白原血症阈值（表示为最大振幅纤维蛋白原，MA-Fib）和术后MA-Fib，纤维蛋白原血症,术中输血,和不良事件（AE）。总的来说,纳入139例接受CPB心脏手术且年龄小于2岁的患者：70例患者接受同种异体血液制品和FC补充（FC组）；69例患者接受同种异体血液制品而不补充FC（无FC组）。接受FC补充的患者的特点是体外循环时间明显更长（p<0.001）和主动脉阻断（p<0.001），显著降低的最低温度（p=0.011），增加使用浓缩凝血酶原复合物（p=0.016）和氨甲环酸（p=0.010），和更大量的红细胞，血小板（p<0.001）和新鲜冷冻血浆（p=0.03）。术后出血和严重出血在接受FC治疗和未接受FC补充治疗的患者之间没有统计学差异（分别为p=0.786和p=0.695）；调整后，FC可观察到出血减少的趋势(p=0.064).总的来说,88％的严重出血患者的MA-Fib<10mm；发现严重出血与MA-Fib之间存在中度关联（比值比1.7，95％CI0.5-6.5，p=0.425）。FC组的MA-Fib和术后纤维蛋白原增加高于FFP（分别为p=0.003和p<0.001）。FC组的AE与较不复杂的手术中观察到的AE相当。我们的结果表明，FC在复杂手术中的潜在作用是将术后出血维持在与较不复杂的手术相当的水平，并有利于术后MA-Fib和纤维蛋白原的增加。
