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

Abstract

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

Vancomycin and Gentamicin Removal with the HA380 Cartridge during Experimental Hemoadsorption

“…A prospective observational study in seven patients with septic shock demonstrated significant adsorption of vancomycin by a resin adsorber cartridge, with a linear decrease during HA with the CytoSorb ® cartridge [6]. The authors proposed an additional 500 mg dose of vancomycin over 2 h at the initiation of HA to compensate for removal by the procedure.…”

Antithrombotic drug removal with hemoadsorption during off-pump coronary artery bypass grafting

“…On the other hand, albumin or coagulation factors are not removed, however, certain drugs, e.g. vancomycin are removed [ 8 ]. A detailed list of adsorbed substances is given in Scheier et al and for specific drugs, therapeutic drug monitoring is recommended [ 9 ].…”

Hemoperfusion in the intensive care unit

“…Evidence assessing the pharmacokinetic behavior of antibiotics typically used in patients undergoing hemoperfusion is limited, and only a few data exist coming from small and heterogeneous studies [67][68][69][70][71][72]. Due to the critical importance of optimal antimicrobial treatment in sepsis, it seems crucial to understand and compensate for such extracorporeal loss during Fig.…”

“…Consequently, additional extra doses of antimicrobials must be administered within the first few hours of initiation of hemoperfusion to maintain a clinically adequate steady-state serum concentration. A recent prospective observational study, designed to quantify the adsorption of vancomycin (as a continuous infusion with a preceding loading dose over 2 h) by CytoSorb ® , demonstrated significant adsorption of vancomycin with a linear decrease during CytoSorb ® treatment [69]. A total of 160 vancomycin serum samples from 7 patients with septic shock were included in the analysis and 15% of the samples were collected during CytoSorb ® treatment.…”