Fundació Privada Clínic per la Recerca Biomèdica, Barcelona, Spain Critical Care Department, Sabadell Hospital, University Institute Parc Taulí - Universitat Autònoma de Barcelona (UAB), Sabadell, Spain Universitat de Barcelona (UB), Barcelona, Spain
Critical Care Department, Sabadell Hospital, University Institute Parc Taulí - Universitat Autònoma de Barcelona (UAB), Sabadell, Spain Multidisciplinary Intensive Care Research Organization (MICRO), Critical Care Department, St James University Hospital, Trinity Centre for Health Sciences, Dublin, Ireland Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
J Antimicrob Chemother. 2016 Jun;71(6):1651-9. doi: 10.1093/jac/dkv503. Epub 2016 Feb 10.
This multicentre study aimed to describe the pharmacokinetics (PK) of piperacillin in critically ill patients with multiple organ dysfunction syndrome (MODS) receiving continuous venovenous haemodiafiltration (CVVHDF), to identify the sources of PK variability and evaluate different dosing regimens to develop recommendations based on clinical parameters.
Nineteen patients with MODS and CVVHDF receiving piperacillin/tazobactam were enrolled from three tertiary hospitals (95 plasma samples). Population PK modelling and Monte Carlo simulations were performed using NONMEM v7.3(®).
Patients' median age was 70 years (range 39-82), median weight was 80 kg (45-129), median APACHE II score at admission was 21 (13-33) and median SOFA score on the day of study was 11 (8-21). The final population PK model was characterized by CL (L/h) = 6.11 * weight (kg)/80 * CLMEMB. If membrane = 1.5 m(2) AN69ST, CLMEMB = 1; if membrane = 0.9 m(2) AN69, CLMEMB = 0.51. Monte Carlo simulations showed that: (i) to maintain unbound piperacillin concentrations above the MIC for the bacteria for 100% of dosing interval T (100%fuT>MIC), patients receiving CVVHDF with 1.5 m(2) AN69ST membranes required doses of 4000 mg q8h for the treatment of bacteria with a susceptibility to piperacillin close to the clinical breakpoint (MIC = 8-16 mg/L) (2000 mg q8h was sufficient for patients with CVVHDF using 0.9 m(2) AN69 membranes); and (ii) for the treatment of bacteria with high susceptibility to piperacillin (MIC <4 mg/L) or for the attainment of a more traditional pharmacodynamic target (50%fuT>MIC), 2000 mg q8h sufficed regardless of type of membrane and body weight.
Our results suggest that type of membrane and body weight should be considered for piperacillin dose titration in critically ill patients with MODS and CVVHDF requirement.
本多中心研究旨在描述接受连续静脉-静脉血液透析滤过（CVVHDF）的多器官功能障碍综合征（MODS）危重症患者哌拉西林的药代动力学（PK），确定 PK 变异性的来源，并评估不同的给药方案，以基于临床参数制定建议。
从三家三级医院（95 个血浆样本）招募了 19 名接受哌拉西林/他唑巴坦治疗的 MODS 合并 CVVHDF 的患者。使用 NONMEM v7.3(®) 进行群体 PK 建模和 Monte Carlo 模拟。
患者的中位年龄为 70 岁（范围 39-82），中位体重为 80kg（45-129），入院时的中位急性生理与慢性健康状况评分系统 II （APACHE II）评分为 21（13-33），研究当天的中位序贯器官衰竭评估（SOFA）评分为 11（8-21）。最终的群体 PK 模型的特点是 CL（L/h）=6.11*体重（kg）/80*CLMEMB。如果膜=1.5 m²AN69ST，则 CLMEMB=1；如果膜=0.9 m²AN69，则 CLMEMB=0.51。Monte Carlo 模拟显示：（i）为了使游离哌拉西林浓度在 100%的给药间隔 T（100%fuT>MIC）期间保持在针对细菌的 MIC 以上，接受 1.5 m²AN69ST 膜的 CVVHDF 治疗的患者需要 4000mg q8h 的剂量，以治疗对哌拉西林敏感性接近临床折点（MIC=8-16mg/L）的细菌（对于接受 0.9 m²AN69 膜的 CVVHDF 治疗的患者，2000mg q8h 就足够了）；（ii）对于治疗对哌拉西林高度敏感的细菌（MIC<4mg/L）或达到更传统的药效学目标（50%fuT>MIC），无论膜的类型和体重如何，2000mg q8h 就足够了。
我们的研究结果表明，在接受 CVVHDF 治疗的 MODS 危重症患者中，应考虑膜的类型和体重来调整哌拉西林的剂量。
