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比伐芦定治疗肝和/或肾功能不全重症患者肝素诱导的血小板减少症的评估。

Evaluation of bivalirudin treatment for heparin-induced thrombocytopenia in critically ill patients with hepatic and/or renal dysfunction.

作者信息

Kiser Tyree H, Fish Douglas N

机构信息

Department of Clinical Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.

出版信息

Pharmacotherapy. 2006 Apr;26(4):452-60. doi: 10.1592/phco.26.4.452.

Abstract

STUDY OBJECTIVE

To evaluate the safety, effectiveness, and dosing of bivalirudin for treatment of heparin-induced thrombocytopenia (HIT) in critically ill patients with hepatic and/or renal dysfunction.

DESIGN

Retrospective cohort study.

SETTING

University-affiliated medical center

PATIENTS

Eighteen patients older than 18 years who were admitted to the intensive care unit (ICU), had hepatic and/or renal dysfunction, and were treated with bivalirudin for the diagnosis of HIT between January 1, 2004, and March 31, 2005.

MEASUREMENTS AND MAIN RESULTS

Patient records were reviewed for dosage and duration of bivalirudin therapy, occurrence of thrombosis, and clinically significant adverse effects. Of the 18 patients identified, 12 had both hepatic and renal dysfunction (group 1), four had hepatic dysfunction (group 2), and two had renal dysfunction (group 3). Demographics were similar among the groups. Mean +/- SD age was 54 +/- 15 years and weight was 82 +/- 14 kg, 67% were male, 83% were Caucasian, and 56% were receiving renal replacement therapy. Mean bivalirudin doses were 0.06 +/- 0.15 mg/kg/hour (median 0.03 mg/kg/hr), 0.14 +/- 0.05 mg/kg/hour (median 0.14 mg/kg/hr), and 0.05 +/- 0.01 mg/kg/hour (median 0.05 mg/kg/hr) for patients in groups 1, 2, and 3, respectively. Ten patients receiving continuous venovenous hemofiltration with or without dialysis received a mean dose of 0.04 +/- 0.03 mg/kg/hour (median 0.03 mg/kg/hr). In the 18 patients, mean bivalirudin duration was 15 +/- 17 days, activated partial thromboplastin time (aPTT) was 69 +/- 22 seconds, and international normalized ratio was 2.2 +/- 0.8. Supratherapeutic aPTTs were most common on days 1 (22%) and 2 (28%) when bivalirudin doses were highest. Clinically significant bleeding did not occur in any patient. Thrombosis occurred in one patient (6%) while receiving bivalirudin.

CONCLUSION

Patients in the ICU who have hepatic and/or renal dysfunction require low doses of bivalirudin to achieve aPTT values 1.5-2.5 times baseline. Bivalirudin can be safely started at 0.14 mg/kg/hour in patients with hepatic dysfunction, 0.03-0.05 mg/kg/hour in those with renal or combined hepatic and renal dysfunction, and 0.03-0.04 mg/kg/hour in patients receiving continuous renal replacement therapy.

摘要

研究目的

评估比伐卢定治疗肝和/或肾功能不全的重症患者肝素诱导的血小板减少症(HIT)的安全性、有效性及剂量。

设计

回顾性队列研究。

地点

大学附属医院医疗中心

患者

2004年1月1日至2005年3月31日期间入住重症监护病房(ICU)、有肝和/或肾功能不全且接受比伐卢定治疗以诊断HIT的18岁以上患者。

测量指标及主要结果

查阅患者记录,了解比伐卢定治疗的剂量、持续时间、血栓形成情况及具有临床意义的不良反应。在确定的18例患者中,12例同时有肝和肾功能不全(第1组),4例有肝功能不全(第2组),2例有肾功能不全(第3组)。各组间人口统计学特征相似。平均年龄±标准差为54±15岁,体重为82±14kg,67%为男性,83%为白种人,56%接受肾脏替代治疗。第1、2、3组患者的比伐卢定平均剂量分别为0.06±0.15mg/kg/小时(中位数0.03mg/kg/小时)、0.14±0.05mg/kg/小时(中位数0.14mg/kg/小时)和0.05±0.01mg/kg/小时(中位数0.05mg/kg/小时)。10例接受持续静静脉血液滤过(伴或不伴透析)的患者平均剂量为0.04±0.03mg/kg/小时(中位数0.03mg/kg/小时)。18例患者中,比伐卢定平均持续时间为15±17天,活化部分凝血活酶时间(aPTT)为69±22秒,国际标准化比值为2.2±0.8。在比伐卢定剂量最高的第1天(22%)和第2天(28%),超治疗性aPTT最为常见。所有患者均未发生具有临床意义的出血。1例患者(6%)在接受比伐卢定治疗时发生血栓形成。

结论

有肝和/或肾功能不全的ICU患者需要低剂量比伐卢定以达到aPTT值为基线值的1.5 - 2.5倍。对于肝功能不全患者,比伐卢定可安全地起始剂量为0.14mg/kg/小时;对于肾功能不全或肝肾功能联合不全患者,为0.03 - 0.05mg/kg/小时;对于接受持续肾脏替代治疗的患者,为0.03 - 0.04mg/kg/小时。

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