接受体外膜肺氧合治疗患者伏立康唑暴露情况的大型回顾性评估
A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation.
作者信息
Van Daele Ruth, Bekkers Britt, Lindfors Mattias, Broman Lars Mikael, Schauwvlieghe Alexander, Rijnders Bart, Hunfeld Nicole G M, Juffermans Nicole P, Taccone Fabio Silvio, Coimbra Sousa Carlos Antônio, Jacquet Luc-Marie, Laterre Pierre-François, Nulens Eric, Grootaert Veerle, Lyster Haifa, Reed Anna, Patel Brijesh, Meersseman Philippe, Debaveye Yves, Wauters Joost, Vandenbriele Christophe, Spriet Isabel
机构信息
Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium.
Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium.
出版信息
Microorganisms. 2021 Jul 20;9(7):1543. doi: 10.3390/microorganisms9071543.
BACKGROUND
Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population.
METHODS
Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit's binding sites over time.
RESULTS
Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO ( = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2-4.7) mg/L under ECMO and 2.5 (1.4-3.9) mg/L without ECMO ( = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure.
CONCLUSIONS
No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.
背景
伏立康唑是侵袭性肺曲霉病的一线治疗药物之一。体外膜肺氧合（ECMO）的使用可能会显著影响药物浓度。我们旨在评估ECMO对大量患者群体中伏立康唑暴露的影响。
方法
本回顾性研究纳入了来自四个国家八个中心在ECMO支持期间接受伏立康唑治疗的重症患者。在ECMO期间以及ECMO治疗前后收集伏立康唑浓度。进行多变量分析以评估ECMO对伏立康唑暴露的影响，并评估随着时间推移回路结合位点可能饱和的影响。
结果
分析了69例患者和337个样本（ECMO期间190个，ECMO治疗前后147个）。在ECMO期间56%的样本和无ECMO时39%的样本中观察到治疗浓度低于2mg/L（P=0.80）。对于相似的每日剂量，ECMO下的中位谷浓度为2.4（1.2 - 4.7）mg/L，无ECMO时为2.5（1.4 - 3.9）mg/L（P=0.58）。观察到广泛的个体间和个体内变异性。ECMO和ECMO的平方天数（饱和度）均未作为伏立康唑暴露的显著协变量保留。
结论
未观察到ECMO对伏立康唑暴露有显著影响。很大一部分患者的伏立康唑浓度低于治疗浓度。
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