Eaton Michael P, Alfieris George M, Sweeney Dawn M, Angona Ronald E, Cholette Jill M, Venuto Charles, Anderson Brian
From the Departments of Anesthesiology (M.P.E., D.M.S.), Surgery (G.M.A., R.E.A.), Pediatrics (J.M.C.), and Neurology, Center for Human Experimental Therapeutics (C.V.), University of Rochester School of Medicine and Dentistry, Rochester, New York; and Department of Anaesthesiology, University of Auckland, Auckland, New Zealand (B.A.).
Anesthesiology. 2015 May;122(5):1002-9. doi: 10.1097/ALN.0000000000000616.
Antifibrinolytic medications such as ε-aminocaproic acid (EACA) are used in pediatric heart surgery to decrease surgical bleeding and transfusion. Dosing schemes for neonates are often based on adult regimens, or are simply empiric, in part due to the lack of neonatal pharmacokinetic information. The authors sought to determine the pharmacokinetics of EACA in neonates undergoing cardiac surgery and to devise a dosing regimen for this population.
Ten neonates undergoing cardiac surgery with cardiopulmonary bypass were given EACA according to standard practice, and blood was drawn at 10 time points to determine drug concentrations. Time-concentration profiles were analyzed using nonlinear mixed effects models. Parameter estimates (standardized to a 70-kg person) were used to develop a dosing regimen intended to maintain a target concentration shown to inhibit fibrinolysis in neonatal plasma (50 mg/l).
Pharmacokinetics were described using a two-compartment model plus an additional compartment for the cardiopulmonary bypass pump. First-order elimination was described with a clearance of 5.07 l/h × (WT/70). Simulation showed a dosing regimen with a loading dose of 40 mg/kg and an infusion of 30 mg · kg · h, with a pump prime concentration of 100 mg/l maintained plasma concentrations above 50 mg/l in 90% of neonates during cardiopulmonary bypass surgery.
EACA clearance, expressed using allometry, is reduced in neonates compared with older children and adults. Loading dose and infusion dose are approximately half those required in children and adults.
抗纤维蛋白溶解药物，如ε-氨基己酸（EACA），用于小儿心脏手术以减少手术出血和输血。新生儿的给药方案通常基于成人方案，或者仅仅是经验性的，部分原因是缺乏新生儿药代动力学信息。作者试图确定EACA在接受心脏手术的新生儿中的药代动力学，并为该人群设计给药方案。
10名接受体外循环心脏手术的新生儿按照标准操作给予EACA，并在10个时间点采集血液以测定药物浓度。使用非线性混合效应模型分析时间-浓度曲线。参数估计值（标准化为70千克体重的人）用于制定给药方案，旨在维持在新生儿血浆中显示可抑制纤维蛋白溶解的目标浓度（50毫克/升）。
药代动力学用二室模型加体外循环泵的附加室来描述。一级消除用清除率5.07升/小时×（体重/70）来描述。模拟显示，在体外循环手术期间，负荷剂量为40毫克/千克、输注量为30毫克·千克·小时、泵预充液浓度为100毫克/升的给药方案能使90%的新生儿血浆浓度维持在50毫克/升以上。
与大龄儿童和成人相比，新生儿中按体表面积比例计算的EACA清除率降低。负荷剂量和输注剂量约为儿童和成人所需剂量的一半。
