Antimicrobial dosing in patients with acute kidney injury requiring renal
replacement therapies is challenging. Generally, renal replacement therapy is either
diffusive or convective. The most commonly used modalities are: Intermittent
Hemodialysis (IHD), Continuous Renal Replacement Therapy - CRRT (continuous
venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD),
and continuous venovenous hemodiafiltration (CVVHDF)), Prolonged Intermittent
Renal Replacement Therapies (PIRRT), and Peritoneal Dialysis (PD). Several factors
affect the transport of the drugs in these dialysis modalities, such as; the drug’s
molecular weight, membrane properties (high-flux or low-flux), protein binding, blood
flow rate, and dialysate flow rate, and dialyzer surface area. The Food and Drug
Administration (FDA) does not mandate manufacturers to provide dosing in different
renal replacement therapy modalities, which overwhelmingly complicate the dosing
strategies of antimicrobials in this population. Furthermore, different CRRT modalities
complicate the dosing with variable prescriptions in which the blood flow rate,
dialysate flow rate, and effluent flow rate might significantly differ based on patients'
needs. Additionally, extrapolation of pharmacokinetics (PK) from normal patient
population and extending it to patients utilizing RRT is a questionable practice. In
addition, the situation gets more complicated when those patients require
extracorporeal membrane oxygenation (ECMO). Predicting the plasma concentrations
of drugs during ECMO is difficult because many factors simultaneously impact the PK
and because inconsistent results have been obtained in PK studies and the significant
heterogeneity of data including medical and surgical patients or patients under
venovenous and venoarterial ECMO in variable proportion. In conclusion, dosing of
antimicrobials in patients receiving RRT or ECMO would require comprehensive
understanding of the antimicrobials’ PK/PD as well as thorough understanding of the
RRT and ECMO techniques and their effects on PK/PD.
