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