Drug dosing considerations in continuous renal replacement therapy

Acute kidney injury (AKI) is a common complication in critically ill patients, which is associated with increased in-hospital mortality. Delivering effective antibiotics to treat patients with sepsis receiving continuous renal replacement therapy (RRT) is complicated by variability in pharmacokinetics, dialysis delivery, lack of primary literature, and therapeutic drug monitoring. Pharmacokinetic alterations include changes in absorption, distribution, protein binding (PB), metabolism, and renal elimination. Drug absorption may be significantly changed due to alterations in gastric pH, perfusion, gastrointestinal motility, and intestinal atrophy. Volume of distribution for hydrophilic drugs may be increased due to volume overload. Estimation of renal clearance is challenged by the effective delivery of RRT. Drug characteristics such as PB, volume of distribution, and molecular weight impact removal of the drug by RRT. The totality of these alterations leads to reduced exposure. Despite our best knowledge, therapeutic drug monitoring of patients receiving continuous RRT demonstrates wide variability in antimicrobial concentrations, highlighting the need for expanded monitoring of all drugs. This review article will focus on changes in drug pharmacokinetics in AKI and dosing considerations to attain antibiotic pharmacodynamic targets in critically ill patients receiving continuous RRT.