From the Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California.
Quantitative Sciences Unit, Department of Medicine, Stanford University School of Medicine, Stanford, California.
Anesth Analg. 2023 Mar 1;136(3):473-482. doi: 10.1213/ANE.0000000000006294. Epub 2022 Dec 2.
Prothrombin complex concentrates are an emerging "off-label" therapy to augment hemostasis after cardiopulmonary bypass (CPB), but data supporting their use for neonatal cardiac surgery are limited.
We retrospectively reviewed neonates undergoing open heart surgery with first-time sternotomy between May 2014 and December 2018 from a hospital electronic health record database. Neonates who received activated 4-factor prothrombin complex concentrate (a4FPCC) after CPB were propensity score matched (PSM) to neonates who did not receive a4FPCC (control group). The primary efficacy outcome was total volume (mL/kg) of blood products transfused after CPB, including the first 24 hours on the cardiovascular intensive care unit (CVICU). The primary safety outcome was the incidence of 7- and 30-day postoperative thromboembolism. Secondary outcomes included 24 hours postoperative chest tube output, time to extubation, duration of CVICU stay, duration of hospital stay, 30-day mortality, and incidence of acute kidney injury on postoperative day 3. We used linear regression modeling on PSM data for the primary efficacy outcome. For the primary safety outcome, we tested for differences using McNemar test on PSM data. For secondary outcomes, we used linear regression, Fisher exact test, or survival analyses as appropriate, with false discovery rate-adjusted P values.
A total of 165 neonates were included in the final data analysis: 86 in the control group and 79 in the a4FPCC group. After PSM, there were 43 patients in the control group and 43 in the a4FPCC group. We found a statistically significant difference in mean total blood products transfused for the a4FPCC group (47.5 mL/kg) compared with the control group (63.7 mL/kg) for PSM patients (adjusted difference, 15.3; 95% CI, 29.4-1.3; P = .032). We did not find a statistically significant difference in 7- or 30-day thromboembolic rate, postoperative chest tube output, time to extubation, incidence of postoperative acute kidney injury (AKI), or 30-day mortality between the groups. The a4FPCC group had a significantly longer length of intensive care unit stay (32.9 vs 13.3 days; adjusted P = .049) and hospital stay (44.6 vs 24.1 days; adjusted P = .049) compared with the control group.
We found that the use of a4FPCC as a hemostatic adjunct for post-CPB bleeding in neonatal cardiac surgery was associated with a decrease in mean total blood products transfused after CPB without an increased rate of 7- or 30-day postoperative thromboembolism. Our findings suggest that a4FPCCs can be considered as part of a hemostasis pathway for refractory bleeding in neonatal cardiac surgery.
在体外循环（CPB）后，凝血酶原复合物浓缩物是一种新兴的“超适应证”治疗方法，可增强止血效果，但支持其用于新生儿心脏手术的数据有限。
我们从医院电子病历数据库中回顾性分析了 2014 年 5 月至 2018 年 12 月间首次行胸骨切开术的接受体外循环后心脏手术的新生儿。CPB 后接受活化的 4 因子凝血酶原复合物浓缩物（a4FPCC）的新生儿与未接受 a4FPCC 的新生儿（对照组）进行倾向评分匹配（PSM）。主要疗效结局是 CPB 后输注的血液制品总量（mL/kg），包括在心血管重症监护病房（CVICU）的前 24 小时。主要安全性结局是术后 7 天和 30 天的血栓栓塞事件发生率。次要结局包括术后 24 小时胸腔引流管引流量、拔管时间、CVICU 住院时间、住院时间、30 天死亡率和术后第 3 天急性肾损伤发生率。我们使用 PSM 数据进行了主要疗效结局的线性回归建模。对于主要安全性结局，我们使用 PSM 数据的 McNemar 检验进行了差异检验。对于次要结局，我们使用了线性回归、Fisher 确切检验或适当的生存分析，并对虚假发现率进行了调整。
最终数据分析共纳入 165 例新生儿：对照组 86 例，a4FPCC 组 79 例。PSM 后，对照组有 43 例，a4FPCC 组有 43 例。我们发现，与对照组相比，PSM 患者的 a4FPCC 组的平均总输血量（47.5 mL/kg）显著减少（调整后差异，15.3；95%CI，29.4-1.3；P=.032）。两组间 7 天或 30 天血栓栓塞率、术后胸腔引流管引流量、拔管时间、术后急性肾损伤（AKI）发生率或 30 天死亡率均无统计学差异。与对照组相比，a4FPCC 组的 ICU 住院时间（32.9 天 vs. 13.3 天；调整后 P=.049）和住院时间（44.6 天 vs. 24.1 天；调整后 P=.049）明显更长。
我们发现，在新生儿心脏手术中，CPB 后使用 a4FPCC 作为辅助止血剂与 CPB 后总输血量减少相关，而术后 7 天或 30 天的血栓栓塞事件发生率没有增加。我们的研究结果表明，a4FPCC 可作为新生儿心脏手术中难治性出血的止血途径之一。
