From the Department of Cardiothoracic Sugery, Promedical Toledo Hospital, Toledo, Ohio.
Bioscience Research Group, Grifols, Barcelona, Spain.
Anesth Analg. 2022 Oct 1;135(4):757-768. doi: 10.1213/ANE.0000000000006145. Epub 2022 Jul 25.
Antithrombin (AT) activity is reduced during cardiac operations with cardiopulmonary bypass (CPB), which is associated with adverse outcomes. Preoperative AT supplementation, to achieve >58% and <100% AT activity, may potentially reduce postoperative morbidity and mortality in cardiac operations with CPB. This prospective, multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of preoperative treatment with AT supplementation in patients at risk for low AT activity after undergoing cardiac surgery with CPB.
A total of 425 adult patients were randomized (1:1) to receive either a single dose of AT (n = 213) to achieve an absolute increase of 20% above pretreatment AT activity or placebo (n = 212) before surgery. The study duration was approximately 7 weeks. The primary efficacy end point was the percentage of patients with any component of a major morbidity composite (postoperative mortality, stroke, acute kidney injury [AKI], surgical reexploration, arterial or venous thromboembolic events, prolonged mechanical ventilation, and infection) in the 2 groups. Secondary end points included AT activity, blood loss, transfusion requirements, duration of intensive care unit (ICU), and hospital stays. Safety was also assessed.
Overall, 399 patients (men, n = 300, 75.2%) with a mean (standard deviation [SD]) age of 66.1 (11.7) years, with the majority undergoing complex surgical procedures (n = 266, 67.9%), were analyzed. No differences in the percentage of patients experiencing morbidity composite outcomes between groups were observed (AT-treated 68/198 [34.3%] versus placebo 58/194 [29.9%]; P = .332; relative risk, 1.15). After AT infusion, AT activity was significantly higher in the AT group (108% [42-143]) versus placebo group (76% [40-110]), and lasted up to postoperative day 2. At ICU, the frequency of patients with AT activity ≥58% in the AT group (81.5%) was significantly higher ( P < .001) versus placebo group (43.2%). Secondary end point analysis did not show any advantage of AT over placebo group. There were significantly more patients with AKI ( P < .001) in the AT group (23/198; 11.6%) than in the placebo group (5/194, 2.6%). Safety results showed no differences in treatment-emergent adverse events nor bleeding events between groups.
AT supplementation did not attenuate adverse postoperative outcomes in our cohort of patients undergoing cardiac surgery with CPB.
体外循环（CPB）心脏手术期间抗凝血酶（AT）活性降低，与不良结局相关。术前 AT 补充，达到>58%和<100%的 AT 活性，可能降低 CPB 心脏手术后的术后发病率和死亡率。本前瞻性、多中心、随机、双盲、安慰剂对照研究旨在评估术前 AT 补充治疗对 CPB 心脏手术后 AT 活性降低风险患者的安全性和疗效。
共纳入 425 例成年患者（1:1），随机（1:1）接受单次 AT 治疗（n=213），以达到治疗前 AT 活性绝对增加 20%，或安慰剂（n=212）术前。研究持续约 7 周。主要疗效终点为两组中任何主要复合发病率（术后死亡率、中风、急性肾损伤[AKI]、手术再探查、动脉或静脉血栓栓塞事件、延长机械通气和感染）患者的百分比。次要终点包括 AT 活性、失血、输血需求、重症监护病房（ICU）持续时间和住院时间。还评估了安全性。
总体而言，399 例患者（男性，n=300，75.2%），平均（标准差[SD]）年龄为 66.1（11.7）岁，大多数患者接受复杂手术（n=266，67.9%），进行了分析。两组间发病率复合结局患者的比例无差异（AT 治疗 198 例[68/198，34.3%]与安慰剂治疗 194 例[58/194，29.9%]；P=.332；相对风险，1.15）。AT 输注后，AT 组 AT 活性显著高于安慰剂组（108%[42-143]与 76%[40-110]），并持续至术后第 2 天。在 ICU，AT 组 AT 活性≥58%的患者频率（81.5%）显著高于安慰剂组（43.2%）（P<.001）。次要终点分析显示 AT 组无任何优势比安慰剂组。AT 组 AKI 患者（P<.001）明显多于安慰剂组（23/198；11.6%）（5/194，2.6%）。安全性结果显示两组间治疗中出现的不良事件或出血事件无差异。
在接受 CPB 心脏手术的患者中，AT 补充并不能减轻术后不良结局。
