Brunet Philippe, Simon Nicolas, Opris Adriana, Faure Valérie, Lorec-Penet Anne-Marie, Portugal Henri, Dussol Bertrand, Berland Yvon
Centre de Néphrologie et de Transplantation Rénale, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
Am J Kidney Dis. 2008 May;51(5):789-95. doi: 10.1053/j.ajkd.2007.12.040.
Anti-Xa activity is used as a clinical guide to anticoagulation with heparin, but heparin dosing regimens for hemodialysis were established before anti-Xa assays were developed; thus, the optimal regimen for heparin dosing was not determined. The aim is to confirm the interesting characteristics of unfractionated heparin pharmacokinetics for hemodialysis anticoagulation, provide insight into the hemorrhagic risk of hemodialysis patients, and determine the dose of unfractionated heparin and its adequate mode of administration.
Cross-sectional study of the pharmacokinetics of unfractionated heparin performed during and after a 4-hour midweek hemodialysis session.
SETTING & PARTICIPANTS: 35 long-term hemodialysis patients at the Sainte-Marguerite Unit of the Marseille University Hospital, Marseille, France.
Hemodialysis anticoagulation with continuous unfractionated heparin infusion at a dose of 50 IU/kg/session (25 IU/kg/h during the first hour, 12.5 IU/kg during the second and third hours, and stop during the last hour).
OUTCOME & MEASUREMENTS: Anti-Xa activity was monitored during the 10 hours after the beginning of the hemodialysis session. Levels of 0.3 to 0.7 IU/mL are considered sufficient for anticoagulation. Pharmacokinetics was determined by using a population approach (nonlinear mixed-effects modeling). The final model and corresponding parameter values (including interindividual and residual variability) were used to simulate 1,000 replicates.
No case of clotting was recorded. A pharmacokinetic model with 1 compartment and first-order elimination best fitted the data. Terminal half-life was 54 minutes. Median anti-Xa activities were 0.55 IU/mL at peak, 0.25 IU/mL at end of the 4-hour session, and less than 0.1 IU/mL at 90 minutes after the session. We simulated a continuous infusion of the dose of 50 IU/kg for 1, 2, 3, and 4 hours. Peak values were 1.1, 0.8, 0.6, and 0.5 IU/mL, respectively. Values at the end of the session were 0.12, 0.18, 0.3, and 0.5 IU/mL, respectively. Values became less than 0.1 IU/mL at 15, 60, 105, and 120 minutes after the session, respectively.
Interindividual variability in unfractionated heparin pharmacokinetics.
Unfractionated heparin administered by means of a 3-hour continuous infusion for hemodialysis anticoagulation provided an efficient and safe effect that quickly disappeared after the end of the session.
抗Xa活性被用作肝素抗凝治疗的临床指导指标，但血液透析的肝素给药方案在抗Xa检测方法开发之前就已确立；因此，肝素给药的最佳方案尚未确定。目的是确认普通肝素用于血液透析抗凝的药代动力学有趣特征，深入了解血液透析患者的出血风险，并确定普通肝素的剂量及其合适的给药方式。
对在周三进行的4小时血液透析过程中和之后进行的普通肝素药代动力学的横断面研究。
法国马赛大学医院圣玛格丽特科室的35名长期血液透析患者。
以50 IU/kg/次的剂量持续输注普通肝素进行血液透析抗凝（第1小时25 IU/kg/h，第2小时和第3小时12.5 IU/kg，最后1小时停止）。
在血液透析开始后的10小时内监测抗Xa活性。0.3至0.7 IU/mL的水平被认为足以抗凝。采用群体方法（非线性混合效应建模）确定药代动力学。最终模型和相应的参数值（包括个体间和残差变异）用于模拟1000次重复。
未记录到凝血病例。具有1个房室和一级消除的药代动力学模型最符合数据。终末半衰期为54分钟。抗Xa活性峰值中位数在峰值时为0.55 IU/mL，4小时疗程结束时为0.25 IU/mL，疗程后90分钟时小于0.1 IU/mL。我们模拟了以50 IU/kg的剂量持续输注1、2、3和4小时。峰值分别为1.1、0.8、0.6和0.5 IU/mL。疗程结束时的值分别为0.12、0.18、0.3和0.5 IU/mL。疗程后分别在15、60、105和120分钟时值降至小于0.1 IU/mL。
普通肝素药代动力学存在个体间变异。
通过3小时持续输注普通肝素进行血液透析抗凝可提供有效且安全的效果，疗程结束后该效果迅速消失。
