Acute Kidney Injury and Kidney Replacement Therapy in the Critically Ill Patient
ii.
Small substances (e.g., urea with an MW of 60 Da) are cleared more rapidly than larger
substances (e.g., drugs with an MW greater than 500 Da).
iii.
The ability of a drug to cross the dialysis filter during CVVHD is called the saturation
coefficient (SA). Equations exist for estimating the SA when published data are unavailable. It
can be calculated as SA = CE/Cp, where CE is the concentration in the effluent (spent dialysate)
fluid and Cp is the concentration in plasma. The CVVHD clearance can then be approximated
by Qd x SA, where Qd is the dialysate flow rate.
CVVHDF
Solute removal during CVVHDF is by diffusion and convection (i.e., both dialysate and
replacement fluids are used).
ii.
Clearances of small substances are about equal to the sum of the clearance from CVVH and
CVVHD separately. However, as MW increases, this correlation no longer holds true.
iii.
Clearance is estimated as CVVHDF = (QUF + Qd) x SA.
| d. | Prolonged intermittent KRT |
|---|
Limited literature is available to guide drug dosing during prolonged intermittent KRT
modalities such as SLED and EDD.
ii.
Extended dialytic therapies of 8-12 hours may alter drug dosing intervals. For example, drugs
with frequent dosing intervals (e.g., time-dependent antibiotics like ฮฒ-lactams) may need to be
administered more often during the run, given by extended infusion, or repeated/readministered
after the prolonged intermittent KRT treatment.
iii.
Solute removal during SLED/EDD is greater than that during CVVHD when estimated over the
same time interval because higher dialysis flow rates are used during SLED/EDD treatments.
iv.
General dosing considerations for SLED
| (a) | The duration of SLED and its flow rates (dialysate, blood) vary between studies and |
|---|
institutions, making a general approach to dosing problematic.
| (b) | In addition, little information is available to guide drug dosing. |
|---|---|
| (c) | Like IHD and continuous KRT, the most important factors determining drug removal are |
protein binding, water solubility, MW (less than 500 kDa), and Vd (less than 0.8โ1 L/kg);
however, attention should also be given to the timing of drug administration relative to the
prolonged intermittent KRT treatment.
Residual renal function may significantly contribute to drug clearance and requires consideration
when determining dosing.
In general, increased dosing for concentration-dependent antibiotics and extended infusion
for time-dependent antibiotics should be used in patients with preserved diuresis (greater
than 500 mL/d) compared with patients with anuria to achieve adequate pharmacokinetic/
pharmacodynamic targets.