Downey Laura A, Moiseiwitsch Nina, Nellenbach Kimberly, Xiang Yijin, Brown Ashley C, Guzzetta Nina A
From the Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.
Department of Anesthesiology, Children's Healthcare of Atlanta, Atlanta, Georgia.
Anesth Analg. 2024 Aug 8. doi: 10.1213/ANE.0000000000007123.
Neonates undergoing cardiac surgery require fibrinogen replacement to restore hemostasis after cardiopulmonary bypass (CPB). Cryoprecipitate is often the first-line treatment, but recent studies demonstrate that fibrinogen concentrate (RiaSTAP; CSL Behring) may be acceptable in this population. This investigator-initiated, randomized trial compares cryoprecipitate to fibrinogen concentrate in neonates undergoing cardiac surgery (ClinicalTrials.gov NCT03932240). The primary end point was the percent change in ex vivo clot degradation from baseline at 24 hours after surgery between groups. Secondary outcomes included intraoperative blood transfusions, coagulation factor levels, and adverse events.
Neonates were randomized to receive cryoprecipitate (control group) or fibrinogen concentrate (study group) as part of a post-CPB transfusion algorithm. Blood samples were drawn at 4 time points: presurgery (T1), after treatment (T2), arrival to the intensive care unit (ICU) (T3), and 24 hours postsurgery (T4). Using the mixed-effect models, we analyzed the percent change in ex vivo clot degradation from a patient's presurgery baseline at each time point. Intraoperative blood product transfusions, coagulation factor levels, perioperative laboratory values, and adverse events were collected.
Thirty-six neonates were enrolled (intent to treat [ITT]). Thirteen patients in the control group and seventeen patients in the study group completed the study per protocol (PP). After normalizing to the patient's own baseline (T1), no significant differences were observed in clot degradation at T2 or T3. At T4, patients in the study group had greater degradation when compared to those in the control group (826.5%, 95% confidence interval [CI], 291.1-1361.9 vs -545.9%, 95% CI, -1081.3 to -10.4; P < .001). Study group patients received significantly less median post-CPB transfusions than control group patients (ITT, 27.2 mL/kg [19.0-36.9] vs 41.6 [29.2-52.4]; P = .043; PP 26.7 mL/kg [18.8-32.2] vs 41.2 mL/kg [29.0-51.4]; P < .001). No differences were observed in bleeding or thrombotic events.
Neonates who received fibrinogen concentrate, as compared to cryoprecipitate, have similar perioperative ex vivo clot degradation with faster degradation at 24 hours postsurgery, less post-CPB blood transfusions, and no increased bleeding or thrombotic complications. Our findings suggest that fibrinogen concentrate adequately restores hemostasis and reduces transfusions in neonates after CPB without increased bleeding or thrombosis risk.
接受心脏手术的新生儿在体外循环（CPB）后需要补充纤维蛋白原以恢复止血功能。冷沉淀通常是一线治疗方法，但最近的研究表明，纤维蛋白原浓缩物（RiaSTAP；CSL Behring公司）在这一人群中可能是可接受的。这项由研究者发起的随机试验比较了冷沉淀与纤维蛋白原浓缩物在接受心脏手术的新生儿中的应用效果（ClinicalTrials.gov标识符：NCT03932240）。主要终点是两组术后24小时体外血块降解率相对于基线的变化百分比。次要结局包括术中输血情况、凝血因子水平和不良事件。
将新生儿随机分为接受冷沉淀（对照组）或纤维蛋白原浓缩物（研究组），作为CPB后输血方案的一部分。在4个时间点采集血样：术前（T1）、治疗后（T2）、进入重症监护病房（ICU）时（T3）和术后24小时（T4）。使用混合效应模型，我们分析了每个时间点患者术前基线体外血块降解率的变化百分比。收集术中血液制品输注情况、凝血因子水平、围手术期实验室值和不良事件。
共纳入36例新生儿（意向性分析[ITT]）。对照组13例患者和研究组17例患者按方案完成了研究（符合方案分析[PP]）。在以患者自身基线（T1）进行标准化后，T2或T3时的血块降解率无显著差异。在T4时，研究组患者的降解率高于对照组（826.5%，95%置信区间[CI]，291.1 - 1361.9 vs -545.9%，95%CI，-1081.3至-10.4；P <.001）。研究组患者CPB后输血的中位数明显少于对照组患者（ITT，27.2 mL/kg[19.0 - 36.9] vs 41.6[29.2 - 52.4]；P =.043；PP 26.7 mL/kg[18.8 - 32.2] vs 41.2 mL/kg[29.0 - 51.4]；P <.001）。在出血或血栓形成事件方面未观察到差异。
与冷沉淀相比，接受纤维蛋白原浓缩物的新生儿围手术期体外血块降解情况相似，但术后24小时降解更快，CPB后输血更少，且出血或血栓形成并发症未增加。我们的研究结果表明，纤维蛋白原浓缩物能充分恢复CPB后新生儿的止血功能并减少输血，且不增加出血或血栓形成风险。
