Continuous Hemofiltration

The procedures for the CVVH study were similar to those described in our previous ex vivo studies [14, 15]. The CL_TM of urea and rezafungin were evaluated with different blood flow rates, Q_uf and hemodiafilters (Table ​(Table1).1). In a closed-loop system, the formed ultrafiltrate was returned to the blood as a post-filter replacement fluid downstream from the post-hemodiafilter blood sampling port. Figure ​Figure11 shows the schematic of the ex vivo post-filter replacement CVVH system. Pre- and post-hemodiafilter blood samples and ultrafiltrate samples were always collected concurrently. Samples were collected after 12 min when ultrafiltration rate was operated at 1 L/h. Then, ultrafiltration rate was changed to 2 L/h. Samples from these 3 ports were collected after 6 min when ultrafiltration rate was operated at 2 L/h. Lastly, ultrafiltration rate was changed to 3 L/h and samples were collected after 4 min. These sampling times were chosen to allow sufficient time for the ultrafiltrate to reflect the rezafungin concentrations arising from each of the different ultrafiltrate rates. Six experiments were conducted for each hemodiafilter, and new hemodiafilters and CRRT apparatus were used for each experiment. Sieving coefficient (S_C) and CL_TM for post-filter replacement were calculated as follows [15]:

Schematic representation of the ex vivo post-filter replacement CVVH system.

Q_b, Q_uf, and types of hemodiafilters that were used for CVVH ex vivo study

Q_b, blood flow rate; Q_uf, ultrafiltration rate.

where C_uf = concentration in the ultrafiltrate

C_a = concentration of solute in the pre-filter

C_v = concentration of solute in the post-filter

where S_C = observed sieving coefficient

Q_uf = ultrafiltration rate.