Population Pharmacokinetics of Vancomycin in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation (an ASAP ECMO Study)
Population Pharmacokinetics of Vancomycin in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation (an ASAP ECMO Study)
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DOI：
10.1128/aac.01377-21
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发表时间：
2022-01-01
影响因子：
4.9
通讯作者：
Roberts, Jason A.
中科院分区：
文献类型：
--
作者：
Cheng, Vesa;Abdul-Aziz, Mohd H.;Roberts, Jason A.
我们的研究旨在描述万古霉素在接受体外膜氧合（ECMO）的危重患者中的群体药代动力学（PK），包括接受联合肾替代治疗（RRT）的危重患者。给药模拟用于推荐最有效和安全的给药方案。使用Pmetrics上的群体PK方法测量和分析了系列万古霉素血浆浓度。最后的模型用于确定在稳态下达到400-700 mg.h/l的曲线下面积（AUC(0-24)）目标暴露的给药方案。22例患者入组，其中11例患者接受了RRT治疗。在非rrt患者中，中位肌酐清除率（CrCL）为75 ml/min，万古霉素的平均日剂量为25.5 mg/kg。万古霉素在两室模型中得到了很好的描述，CrCL、RRT的存在和总体重被发现是清除率和中心分布容积（V-c）的重要预测因子。万古霉素肾清除率和V-c平均值分别为3.20升/h和29.7升，而RRT组的清除率为0.15升/h。ECMO变量并没有改善最终的协变量模型。我们发现，推荐给未接受ECMO的危重成人患者的剂量方案可以安全有效地用于接受ECMO的危重成人患者。在肾功能正常的患者中，负荷剂量至少为25mg /kg，然后每12小时维持剂量为12.5- 20mg /kg，与97-98%的疗效概率和11-12%的毒性概率相关。治疗药物监测和减少剂量是有必要的患者肾功能损害和那些伴有RRT。
Our study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analyzed using a population PK approach on Pmetrics. The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC(0-24)) of 400-700 mg.h/liter at steady state. Twenty-two patients were enrolled, of which 11 patients received concomitant RRT. In the non-RRT patients, the median creatinine clearance (CrCL) was 75 ml/min and the mean daily dose of vancomycin was 25.5 mg/kg. Vancomycin was well described in a two-compartment model with CrCL, the presence of RRT, and total body weight found as significant predictors of clearance and central volume of distribution (V-c). The mean vancomycin renal clearance and V-c were 3.20 liters/h and 29.7 liters respectively, while the clearance for patients on RRT was 0.15 liters/h. ECMO variables did not improve the final covariate model. We found that recommended dosing regimens for critically ill adult patients not on ECMO can be safely and effectively used in those on ECMO. Loading doses of at least 25 mg/kg followed by maintenance doses of 12.5-20 mg/kg every 12 h are associated with a 97-98% probability of efficacy and 11-12% probability of toxicity, in patients with normal renal function. Therapeutic drug monitoring along with reductions in dosing are warranted for patients with renal impairment and those with concomitant RRT.