Know the Drugs that Must be Redosed after Dialysis
Edward T. Horn PharmD
Acute renal failure is a common disease encountered in critically ill patients, with reported incidences of 5% to 10%. Hemodialysis and continuous venovenous hemodialysis (CVVHD) are commonly used in intensive care unit (ICU) patients to treat acute renal failure, and there are data to suggest that increasing the dose of dialysis can improve mortality outcomes in these patients. It is common sense that as the dose of dialysis is increased, clearance will increase, and therefore medications will need to be dosed more frequently. When considering this issue, one must evaluate various drug characteristics that will require more frequent dosing and close monitoring for therapeutic failure.
What to Do
When evaluating drug regimen adjustments in acute renal failure patients on hemodialysis or CVVHD, one must first consider whether or not the drug is significantly cleared through the kidneys. If the drug has less than 30% of its dose cleared renally, then dialysis is unlikely to play a significant role in its elimination. Other drug characteristics that play a significant role in determining the effect of dialysis on the need to redose a medication include protein binding, volume of distribution (Vd), molecular size, and molecular charge.
With respect to protein binding, only the unbound, or free, concentration is available to be dialyzed out of the blood. Drugs that are >80% bound are unlikely to be cleared by dialysis. Many physiologic derangements can influence drug binding, such as acidosis, uremia, hypoalbuminemia, and hyperbilirubinemia. Drug interactions can also cause displacement of bound drug through competition for binding sites (sulfamethoxazole and trimethoprim are classic culprits of this). While free drug is more available to exert its pharmacologic activity, it is also available to be cleared as well.
Volume of distribution can be considered synonymous with plasma protein binding in that only free drug available in the blood can be cleared by hemodialysis or CVVHD. Drugs with large volumes of distribution or increased lipophilicity or tissue binding will have relatively small concentrations in the serum compared with the
total-body concentration. In general, drugs with Vd >0.7 L/kg will be less likely to be effectively dialyzed with hemodialysis. This is because of the usual short duration of hemodialysis, which allows for a redistribution phenomenon to occur where drug from the tissues will distribute back to the serum after the cessation of hemodialysis. Clearance of these types of drugs will be increased with CVVHD because of the slow, continuous nature of this modality that allows for a continuous removal of drug from the serum. An example that illustrates this is the vancomycin dosing differences between hemodialysis and CVVHD. Vancomycin has a Vd of 0.7 L/kg and usually requires dosing once per week with regular hemodialysis schedules (4 hours per day, 3 times per week). With CVVHD, vancomycin doses are usually required every 36 to 48 hours.
total-body concentration. In general, drugs with Vd >0.7 L/kg will be less likely to be effectively dialyzed with hemodialysis. This is because of the usual short duration of hemodialysis, which allows for a redistribution phenomenon to occur where drug from the tissues will distribute back to the serum after the cessation of hemodialysis. Clearance of these types of drugs will be increased with CVVHD because of the slow, continuous nature of this modality that allows for a continuous removal of drug from the serum. An example that illustrates this is the vancomycin dosing differences between hemodialysis and CVVHD. Vancomycin has a Vd of 0.7 L/kg and usually requires dosing once per week with regular hemodialysis schedules (4 hours per day, 3 times per week). With CVVHD, vancomycin doses are usually required every 36 to 48 hours.
