Boucher Bradley A, Hudson Joanna Q, Hill David M, Swanson Joseph M, Wood G Christopher, Laizure S Casey, Arnold-Ross Angela, Hu Zhe-Yi, Hickerson William L
Department of Clinical Pharmacy, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.
Firefighters' Regional Burn Center, Regional One Health, Memphis, Tennessee.
Pharmacotherapy. 2016 Dec;36(12):1229-1237. doi: 10.1002/phar.1866. Epub 2016 Dec 4.
High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH.
Prospective clinical pharmacokinetic study.
Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied.
Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CL ), CL by CVVH (CL ), half-life during CVVH, volume of distribution at steady state (Vd ), and the percentage of drug eliminated by CVVH.
In this patient sample, the mean age was 50 ± 17 years, total body surface area burns was 23 ± 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 ± 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CL was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CL (14.74 ± 4.75 L/hr). Cilastatin CL was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CL (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 ± 0.38 hours and 4.21 ± 2.31 hours, respectively. Imipenem and cilastatin Vd were 35.1 ± 10.3 and 32.8 ± 13.8 L, respectively.
Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen.
高剂量持续静静脉血液滤过（CVVH）是一种常用于烧伤患者的连续性肾脏替代治疗（CRRT）。然而，抗生素剂量是基于对评估CRRT方法差异很大的研究进行推断得出的。为了填补亚胺培南/西司他丁（I/C）这方面的知识空白，我们评估了接受高剂量CVVH的烧伤患者中I/C的全身清除率和体外清除率（CL）。
前瞻性临床药代动力学研究。
研究了10例因记录在案的感染接受I/C治疗且需要高剂量CVVH的成年烧伤患者。
在输注I/C后长达6小时内采集血液和流出液样本以分析I/C浓度，用于计算I/C的总清除率（CL）、CVVH清除率（CL）、CVVH期间的半衰期、稳态分布容积（Vd）以及CVVH清除的药物百分比。
在该患者样本中，平均年龄为50±17岁，全身烧伤面积为23±27%，80%为男性。9例患者因急性肾损伤接受高剂量CVVH治疗，1例患者因败血症接受治疗。平均给予的CVVH剂量为52±14 ml/kg/小时（范围32 - 74 ml/kg/小时）。亚胺培南的CL为3.27±0.48 L/小时，占总清除率（14.74±4.75 L/小时）的23±4%。西司他丁的CL为1.98±0.56 L/小时，占总清除率（5.16 + 2.44 L/小时）的45±19%。亚胺培南和西司他丁的半衰期分别为1.77±0.38小时和4.21±2.31小时。亚胺培南和西司他丁的Vd分别为35.1±10.3 L和32.8±13.8 L。
在接受这种CRRT方法的烧伤重症监护病房患者中，高剂量CVVH对I/C的有效清除、较高的总体清除率以及较大的分布容积，这就需要根据感染部位和/或病原体进行积极给药以有效治疗严重感染。
