Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass
Rapid disappearance of protamine in adults undergoing cardiac operation with cardiopulmonary bypass
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DOI：
10.1016/s0003-4975(02)04016-x
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发表时间：
2002-11-01
影响因子：
4.6
通讯作者：
James, RL
中科院分区：
文献类型：
--
作者：
Butterworth, J;Lin, YA;James, RL
背景尽管长期使用鱼精蛋白在心脏手术中，鱼精蛋白的浓度和药代动力学都没有报告的病人。28例接受各种心脏外科手术的患者（年龄26 - 80岁）同意在5分钟内通过输液泵静脉注射250 mg硫酸鱼精蛋白。在与体外循环分离后的常规术中时间给予鱼精蛋白，以逆转肝素。在谷醇溶蛋白输注后获得定时动脉血样。血浆进行固相萃取和高效液相色谱法。总（游离+肝素结合）鱼精蛋白浓度与时间的数据进行药代动力学建模。26名患者完成了研究。总血浆鱼精蛋白浓度迅速下降。非模型依赖性药代动力学分析显示中位值（范围）如下：分布容积，5.4 L（0.82 - 34 L）;清除率，1.4 L/min（0.61 - 3.8 L/min）;半衰期，4.5 min（1.9 - 18 min）。Schwarz-Bayesian标准确定了一个二室指数模型，并在中央室分布容积中调整了重量，其表现优于其他房室模型或Michaelis-Menten模型。成人患者单次服用250 mg后，鱼精蛋白的半衰期非常短（约5分钟）。这种短半衰期可能是肝素初始明显逆转后反复抗凝的基础。(C)2002年由胸外科医师协会出版。
Background. Despite long use of protamine in cardiac operations, neither protamine concentrations nor pharmacokinetics have been reported in patients.Methods. Twenty-eight patients (age, 26 to 80 years) undergoing various cardiac surgical procedures gave their consent to receive 250 mg of protamine sulfate administered intravenously by an infusion pump during 5 minutes. Protamine was administered at the usual intraoperative time after separation from cardiopulmonary bypass for reversal of heparin. Timed arterial blood samples were obtained after prolamine infusion. Blood plasma was subjected to solid-phase extraction and high-performance liquid chromatography. Total (free + heparin-bound) protamine concentration versus time data were subjected to pharmacokinetic modeling.Results. Twenty-six patients completed the study. To-tal plasma protamine concentrations declined rapidly. Model-independent pharmacokinetic analysis revealed median (range) values as follows: volume of distribution, 5.4 L (0.82 to 34 L); clearance, 1.4 L/min (0.61 to 3.8 L/min); and half-life, 4.5 min (1.9 to 18 min). Schwarz-Bayesian criterion identified a two-compartment exponential model with adjustment for weight in the central compartment volume of distribution as performing better than other compartmental or Michaelis-Menten models.Conclusions. Protamine has a very short (approximately 5 minutes) half-life after a single 250-mg dose in adult patients. This short half-life could underlie recurrent anticoagulation after initial apparent reversal of heparin. (C) 2002 by The Society of Thoracic Surgeons.