Pharmacokinetics and pharmacodynamics in extracorporeal renal replacement therapy

Intermittent hemodialysis, continuous hemofiltration and prolonged daily dialysis are used for renal replacement therapy in the intensive care units. Independent of the replacement modality, antibiotic therapy must start with a high loading dose. Dose adjustment to the kidneys must follow 48x202f;h later to prevent toxic accumulation. Dose recommendations on product labels are often underdosed. On continuous hemofiltration, meanwhile many intensivists administer a normal standard dose because the high filtration rate corresponds to a half-normal glomerular filtration rate. After intermittent hemodialysis, a dose similar to the loading dose will be needed. On day off dialysis, the maintenance dose must be adjusted to the failing kidney function. Immediately after prolonged daily dialysis, a loading dose should be given; with twice daily dosing the maintenance dose needs to be adjusted to kidney function. Therapeutic drug monitoring is recommended for gentamicin, vancomycin, piperacillin, meropenem and voriconazole. Due to pharmacodynamic reasons, the target concentration corresponds to the concentration producing the half-maximum effect. Accordingly, the target concentration is the normal peak for concentration-dependent action with bolus dosing. The target is the average steady-state concentration for antibiotics with time-dependent action and continuous infusion.