University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queenslandgrid.1003.2University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The grid.1003.2, Brisbane, Queensland, Australia.
Adult Intensive Care Services and Critical Care Research Group, The Prince Charles Hospital, Brisbane, Queensland, Australia.
Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0137721. doi: 10.1128/AAC.01377-21. Epub 2021 Oct 11.
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 . The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC) 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 (). The mean vancomycin renal clearance and 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. (This study is registered with the Australian New Zealand Clinical Trials Registry [ANZCTR] under number ACTRN12612000559819.).
我们的研究旨在描述接受体外膜氧合 (ECMO) 治疗的危重症患者（包括同时接受肾脏替代治疗 (RRT) 的患者）中万古霉素的群体药代动力学 (PK)。我们使用剂量模拟来推荐最大有效和安全的给药方案。使用群体 PK 方法对连续的万古霉素血浆浓度进行测量和分析。最终模型用于确定在稳态时达到 AUC 目标暴露 400-700mg·h/L 的给药方案。共纳入 22 例患者，其中 11 例患者同时接受 RRT。在非 RRT 患者中，中位数肌酐清除率 (CrCL) 为 75ml/min，万古霉素的平均日剂量为 25.5mg/kg。万古霉素在两室模型中得到了很好的描述，CrCL、RRT 的存在以及总体重被认为是清除率和中央分布容积的重要预测因素。万古霉素的平均肾清除率和分别为 3.20 升/小时和 29.7 升，而 RRT 患者的清除率为 0.15 升/小时。ECMO 变量并未改善最终协变量模型。我们发现，对于未接受 ECMO 的危重症成年患者，推荐的给药方案可安全有效地用于接受 ECMO 的患者。对于肾功能正常的患者，至少 25mg/kg 的负荷剂量，随后每 12 小时维持剂量 12.5-20mg/kg，可使疗效的概率达到 97-98%，毒性的概率达到 11-12%。对于肾功能受损的患者和同时接受 RRT 的患者，需要进行治疗药物监测并减少剂量。（本研究在澳大利亚和新西兰临床试验注册中心（ANZCTR）注册，注册号为 ACTRN12612000559819.）。
