Does the cytokine adsorber CytoSorb® reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study,Annals of Intensive Care

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Does the cytokine adsorber CytoSorb® reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study
Annals of Intensive Care ( IF 5.7 ) Pub Date : 2022-05-23 , DOI: 10.1186/s13613-022-01017-5
Christina Scharf ₁ , Ferdinand Weinelt _{2,

3} , Ines Schroeder ₁ , Michael Paal ₄ , Michael Weigand ₄ , Michael Zoller ₁ , Michael Irlbeck ₁ , Charlotte Kloft ₂ , Josef Briegel ₁ , Uwe Liebchen _{1,

2}

Affiliation

Background

Hemadsorption of cytokines is used in critically ill patients with sepsis or septic shock. Concerns have been raised that the cytokine adsorber CytoSorb^® unintentionally adsorbs vancomycin. This study aimed to quantify vancomycin elimination by CytoSorb^®.

Methods

Critically ill patients with sepsis or septic shock receiving continuous renal replacement therapy and CytoSorb^® treatment during a prospective observational study were included in the analysis. Vancomycin pharmacokinetics was characterized using population pharmacokinetic modeling. Adsorption of vancomycin by the CytoSorb^® was investigated as linear or saturable process. The final model was used to derive dosing recommendations based on stochastic simulations.

Results

20 CytoSorb^® treatments in 7 patients (160 serum samples/24 during CytoSorb^®-treatment, all continuous infusion) were included in the study. A classical one-compartment model, including effluent flow rate of the continuous hemodialysis as linear covariate on clearance, best described the measured concentrations (without CytoSorb^®). Significant adsorption with a linear decrease during CytoSorb^® treatment was identified (p < 0.0001) and revealed a maximum increase in vancomycin clearance of 291% (initially after CytoSorb^® installation) and a maximum adsorption capacity of 572 mg. For a representative patient of our cohort a reduction of the area under the curve (AUC) by 93 mg/L*24 h during CytoSorb^® treatment was observed. The additional administration of 500 mg vancomycin over 2 h during CytoSorb^® attenuated the effect and revealed a negligible reduction of the AUC by 4 mg/L*24 h.

Conclusion

We recommend the infusion of 500 mg vancomycin over 2 h during CytoSorb^® treatment to avoid subtherapeutic concentrations.

Trial registration NCT03985605. Registered 14 June 2019, https://clinicaltrials.gov/ct2/show/NCT03985605

中文翻译：

细胞因子吸附剂 CytoSorb® 是否会降低脓毒症或感染性休克重症患者的万古霉素暴露量？一项前瞻性观察研究

背景

细胞因子的血液吸附用于脓毒症或脓毒性休克的重症患者。有人担心细胞因子吸附剂 CytoSorb ^®会无意中吸附万古霉素。本研究旨在量化 CytoSorb ^®对万古霉素的消除作用。

方法

^{在一项前瞻性观察研究中接受连续肾脏替代治疗和 CytoSorb ®}治疗的败血症或感染性休克重症患者被纳入分析。使用群体药代动力学模型表征万古霉素药代动力学。CytoSorb® 对万古霉素的吸附^作为线性或饱和过程进行了研究。最终模型用于根据随机模拟得出剂量建议。

结果

7 名患者的20 次 CytoSorb ^®治疗（160 份血清样本/24 在 CytoSorb ^®治疗期间，所有持续输注）被纳入研究。经典的单室模型，包括连续血液透析的流出物流速作为清除率的线性协变量，最好地描述了测量的浓度（没有 CytoSorb ^®）。^{发现在 CytoSorb ®}处理期间具有线性下降的显着吸附（p < 0.0001）并显示万古霉素清除率的最大增加为 291%（最初在 CytoSorb ^®安装后）和 572 mg 的最大吸附容量。对于我们队列的代表性患者，CytoSorb 期间曲线下面积 (AUC) 减少了 93 mg/L*24 h^®治疗进行了观察。^{在 CytoSorb ®}期间在 2 小时内额外给予 500 mg 万古霉素减弱了效果，并显示 AUC 减少了 4 mg/L*24 小时，可以忽略不计。