Comparison of adsorption of selected antibiotics on the filters in continuous renal replacement therapy circuits: in vitro studies

Abstract

The aim of this study was to assess the adsorption of selected antibiotics: vancomycin, gentamicin, ciprofloxacine and tigecycline in an experimental continuous veno-venous hemofiltration circuit with the use of both polyethyleneimine-treated polyacrylonitrile (PAN) and the polysulfone (PS) filter membranes. The crystalloid fluid dosed with one of antibiotic was pumped from a reservoir through a hemofiltration circuit (with PAN or PS membrane) and back to reservoir. All ultrafiltrate was also returned to the reservoir. During the procedures samples were collected from the post-hemofilter port at 5, 15, 30, 45, 60, 90, and 120 min. To determine spontaneous degradation of the antimicrobials, an additional bag with each study drug was prepared, which was not attached to the hemofiltration circuit. The samples from these bags were used as controls. In the case of vancomycin, gentamycin and tigecycline there was a statistically significant decrease in the drug concentration in the hemofiltration circuit in comparison to the control for PAN membrane (P < 0.05, P < 0.001, P < 0.001, respectively). In the case of ciprofloxacine adsorption was reversible and the drug concentrations increase to achieve the initial level for both membranes. Our studies indicated that a large portion of the administered dose of antibiotics may be adsorbed on a PAN membrane. In the case of gentamicin and tigecycline this amount is sufficiently big (over 90% of the administered dose) to be of clinical importance. In turn, adsorption on PS membranes is clearly lower (up to 10%) and may be clinically unimportant.

Pharmacokinetics and dialytic clearance of apixaban during in vitro continuous renal replacement therapy

“…Albeit the use of modern, highly biocompatible hemofilters has often made drug adsorption negligible compared to the effect of filtration, it is critical to evaluate this component of removal from the circuit especially for moderately water soluble, lipophilic drugs like apixaban. Given that peak adsorption almost always occurs within the first 5–30 min of CRRT [ 66 , 80 , 81 ], our 180 min experiments allowed ample time for the deposition of blood proteins to the hemofilter and circuit in order to assess the reversibility or saturation point of apixaban adsorption [ 82 ]. We observed degrees of filter adsorption high enough to potentially effect drug dosing during CRRT in addition to filtration, particularly for the HF1400 filter, which necessitated filter-specific dosing recommendations as displayed in Table 5 .…”

Pharmacokinetics and Dialytic Clearance of Apixaban During In Vitro Continuous Renal Replacement Therapy

“…Albeit the use of modern, highly biocompatible hemo lters has often made drug adsorption negligible compared to the effect of ltration, it is critical to evaluate this component of removal from the circuit especially for moderately water soluble, lipophilic drugs like apixaban. Given that peak adsorption almost always occurs within the rst 5-30 minutes of CRRT [66,80,81], our 180 minute experiments allowed ample time for the deposition of blood proteins to the hemo lter and circuit in order to assess the reversibility or saturation point of apixaban adsorption [82]. We observed degrees of lter adsorption high enough to potentially effect drug dosing during CRRT in addition to ltration, particularly for the HF1400 lter, which necessitated lter-speci c dosing recommendations as displayed in Table 5.…”

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy

“…Among these membranes, polyacrylonitrile membranes have a hydrogen structure made of acrylonitrile/methallyl sulfonate copolymers, could absorb a large amount of proteins (Michikoshi et al, 2019). Compared with polysulfone, polyacrylonitrile filter membranes absorbed a large portion of the administered dose of antibiotics, such as gentamicin and tigecycline (Onichimowski et al, 2020a). Additionally, the surface area of the CRRT filters significantly increased from 0.6-0.9 to 1.2-1.5 m 2 over the past few years (Onichimowski et al, 2020a).…”

“…Compared with polysulfone, polyacrylonitrile filter membranes absorbed a large portion of the administered dose of antibiotics, such as gentamicin and tigecycline (Onichimowski et al, 2020a). Additionally, the surface area of the CRRT filters significantly increased from 0.6-0.9 to 1.2-1.5 m 2 over the past few years (Onichimowski et al, 2020a). A recent study demonstrated that patients receiving CVVHDF with 1.5 m 2 AN69ST membranes required higher piperacillin/tazobactam doses than 0.9 m 2 membranes (Ulldemolins et al, 2016).…”