Division of Cardiovascular Anesthesia, Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD.
Department of Pharmacy Practice and Science, Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, MD.
J Cardiothorac Vasc Anesth. 2021 Feb;35(2):406-417. doi: 10.1053/j.jvca.2020.07.048. Epub 2020 Jul 21.
To investigate the pharmacokinetics and pharmacodynamics of an ε-aminocaproic acid (EACA) regimen designed for cardiac surgery with cardiopulmonary bypass (CPB).
Prospective observational study requiring blood sampling to measure EACA concentrations and fibrinolysis markers (fibrinogen, D-dimer, α-antiplasmin, and tissue plasminogen activator-plasminogen activator inhibitor [tPA-PAI-1] complex).
Single-center, tertiary medical center.
Patients who underwent cardiac surgery with CPB between 2018 and 2019 for aortic or mitral valve replacement/repair or coronary artery bypass grafting. Previous sternotomy patients were included.
None.
The pharmacokinetics of EACA, during CPB, were described by a 3-compartment disposition model. EACA concentrations were greater than 130 mg/L in all patients after CPB and in most patients during CPB. The D-dimer level trended up and reached a peak median level of 1.35 mg/L of fibrinogen equivalence units (FEU) at 15 minutes after protamine administration. The median change in D-dimer (ΔD-dimer) from baseline to 15 minutes after protamine was 0.34 (-0.48 to 3.81) mg/L FEU. ΔD-dimer did not correlate with EACA concentration intraoperatively, urine output, body weight, glomerular filtration rate, cell salvage volume, and ultrafiltration volume. The median 24-hour chest tube output was 445 (180-1,011) mL.
This regimen provided maximum EACA concentrations near the time of protamine administration, with a total perioperative dose of 15 g. Most patients had EACA concentrations greater than the target during CPB. ΔD-dimer did not correlate with EACA concentration. The median 24-hour chest tube output compared well to similar studies that used higher doses of EACA.
研究含ε-氨基己酸（EACA）的给药方案在体外循环（CPB）心脏手术中的药代动力学和药效学。
前瞻性观察研究，需要采血以测量 EACA 浓度和纤溶标志物（纤维蛋白原、D-二聚体、α-抗纤溶酶和组织型纤溶酶原激活物-纤溶酶原激活物抑制剂复合物（tPA-PAI-1 复合物））。
单中心三级医疗中心。
2018 年至 2019 年间因主动脉瓣或二尖瓣置换/修复或冠状动脉旁路移植术而接受 CPB 心脏手术的患者。包括先前行过正中开胸术的患者。
无。
CPB 期间 EACA 的药代动力学通过 3 室分布模型描述。CPB 后所有患者的 EACA 浓度均大于 130mg/L，且大多数患者在 CPB 期间的浓度大于 130mg/L。D-二聚体水平呈上升趋势，在鱼精蛋白给药后 15 分钟达到 1.35mg/L 纤维蛋白原当量单位（FEU）的中位数峰值。鱼精蛋白给药后 15 分钟 D-二聚体（ΔD-二聚体）的中位数变化为 0.34（-0.48 至 3.81）mg/L FEU。ΔD-二聚体与术中 EACA 浓度、尿量、体重、肾小球滤过率、细胞回收量和超滤量均无相关性。24 小时胸腔引流量中位数为 445（180-1011）mL。
该方案在给予鱼精蛋白的同时提供了接近最大的 EACA 浓度，总围手术期剂量为 15g。大多数患者在 CPB 期间的 EACA 浓度大于目标值。ΔD-二聚体与 EACA 浓度无相关性。24 小时胸腔引流量的中位数与使用更高剂量 EACA 的类似研究相比结果良好。
