背景:在过去的十年中,在新生儿和儿科短期和长期机械支持替代获得性缺陷的过程中,重组抗凝血酶III(AT-III)的使用有所增加.重组AT-III(血栓)给药是FDA许可的药物,主要用于遗传性缺陷患者治疗和预防血栓栓塞,其次用于预防围手术期和围产期血栓栓塞。在此,我们建议进一步使用血栓来治疗新生儿原发性AT-III缺乏症以及体外循环(CPB)继发的获得性稀释和消耗。
方法:所有接受CPB的患者术前获得AT-III水平。使用重组AT-III作为患者负荷,已确定缺陷的患者在OR中正常化,在CPB的巅峰时期,或者两者兼而有之。在暴露于AT-III之前,使用肝素管理系统(HMS)评估患者基线肝素剂量反应(HDR)。如果给予患者AT-III负荷,获得第二HDR,并且该AT-III校正的HDR被用作CPB期间的主要目标。一旦CPB启动,通过第一患者血液分析获得AT-III水平。亚治疗水平导致AT-III的额外剂量。在预热期间,获得最终AT-III水平,如果亚治疗,则再次治疗AT-III。回顾,对两组的实践进行匹配分析回顾,研究组(重复HDR,2022年5月开始)和匹配组(不重复HDR,2019年7月至2022年4月),年龄(D),重量(Kg)和操作进行。研究的重点是确定在HDR(U/mL)中AT-III患者推注负荷后确定的肝素敏感性的任何变化,斜率(U/mL/s),ACT(s),和CPB上的肝素总量(U)和鱼精蛋白(mg)在每组中使用。
结果:在基线AT-III(%)中没有发现显著性,肝素负荷后HDR(U/mL),第一次CPBACT,第一次CPBHDR(U/mL),两组间CPB或总肝素(u/Kg)。统计学显著性可见于基线ACT(s),基线HDR(U/mL),基线斜率(U/mL/s),肝素加载后ACT(s),第一次CPBAT-III(%),和鱼精蛋白(mg/Kg)(p<.05)。在ACT(s)中,在AT-III患者负荷基线样本前与后之间的研究内组中没有观察到统计学意义,然而,在HDR(U/mL)和Slope(U/mL/s)中观察到显著性(p<0.05)。
结论:在CPB之前和期间与HMS联合实施AT-III监测和治疗可以使患者维持稳定的抗凝状态,总体上减少过度肝素替代和潜在的凝血酶激活。结果是获得稳定的抗凝状态,肝素和ACT水平波动减少,与CPB时间延长相关的合并症可能降低.
BACKGROUND: Over the past decade, there has been an increase in the use of recombinant Anti-Thrombin III (AT-III) administration during neonatal and pediatric short- and long-term mechanical support for the replacement of acquired deficiencies. Recombinant AT-III (Thrombate) administration is an FDA licensed drug indicated primarily for patients with hereditary deficiency to treat and prevent thromboembolism and secondarily to prevent peri-operative and peri-partum thromboembolism. Herein we propose further use of Thrombate for primary AT-III deficiency of the newborn as well as for acquired dilution and consumption secondary to cardiopulmonary bypass (CPB).
METHODS: All patients undergoing CPB obtain a preoperative AT-III level. Patients with identified deficiencies are normalized in the OR using recombinant AT-III as a patient load, in the CPB prime, or both. Patient baseline Heparin Dose Response (HDR) is assessed using the Heparin Management System (HMS) before being exposed to AT-III. If a patient load of AT-III is given, a second HDR is obtained and this AT-III Corrected HDR is used as the primary goal during CPB. Once CPB is initiated, an AT-III level is obtained with the first patient blood analysis. A subtherapeutic level results in an additional dose of AT-III. During the rewarm period, a final AT-III level is obtained and AT-III treated once again if subtherapeutic. A retrospective, matched analysis
review of practice analyzing two groups, a Study Group (Repeat HDR, May 2022 onward) and Matched Group (Without Repeat HDR, July 2019 to April 2022), for age (D), weight (Kg) and operation was conducted. The focus of the study was to determine any change in heparin sensitivity identified post AT-III patient bolus load in the HDR (U/mL), Slope (U/mL/s), ACT (s), and total amount of heparin on CPB (U) and protamine (mg) used in each group.
RESULTS: No significance was seen in Baseline AT-III (%), post heparin load HDR (U/mL), first CPB ACT (s), first CPB HDR (U/mL), or total CPB heparin (u/Kg) between the two groups. Statistical significance was seen in Baseline ACT (s), Baseline HDR (U/mL), Baseline Slope (U/mL/s), Post Heparin Load ACT (s), first CPB AT-III (%), and Protamine (mg/Kg) (p < .05). No statistical significance was seen in the Study Intragroup between pre versus post AT-III patient load baseline sample in ACT (s), however significance was seen in HDR (U/mL) and Slope (U/mL/s) (p < .05).
CONCLUSIONS: Implementation of AT-III monitoring and therapy before and during CPB in conjunction with the HMS allows patients to maintain a steady state of anticoagulation with overall less need for excessive heparin replacement and potentially thrombin activation. The result is obtaining a steady state of anticoagulation, a reduced fluctuation in the heparin and ACT levels and a potential for lower co-morbidities associated with prolonged CPB times.