Does the cytokine adsorber CytoSorb^® reduce vancomycin exposure in critically ill patients with sepsis or septic shock? a prospective observational study

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