Acute Kidney Injury and Kidney Replacement Therapy in the Critically Ill Patient

Sustained low-efficiency dialysis (SLED), sustained low-efficiency daily diafiltration (SLEDD-f),

extended daily dialysis (EDD), and accelerated veno-venous hemofiltration are all referred to as prolonged

intermittent renal replacement therapy and are considered hybrid modalities between intermittent and

continuous options.

blood-pump speeds (around 200 mL/min) and low dialysate flow rates (around 300 mL/min) for extended

periods: 6 to 12 hours per day versus 3 to 4 hours for IHD or 24 hours for continuous KRT.

Similar to continuous KRT, they allow for improved hemodynamic stability by producing gradual solute

and volume removal compared with IHD.

These therapies have certain advantages over continuous KRT. They produce high solute clearances, use

existing IHD machines, eliminate the need for external solutions, and allow “time away” when various

diagnostic and therapeutic procedures are needed, liberating health care workers from continuous

involvement with the circuit. Disadvantages include limited data on drug clearance and a period in

which solute and fluid management is paused (when off circuit).

Choosing a Mode

Data are conflicting regarding the renal replacement mode of choice for critically ill patients.

KRT; however, most studies are limited by design, patient characteristics, and crossover between

different modalities.

Drug dosing during continuous KRT and SLED is often unclear because this information is not included

in package inserts. Manufacturers are not required to study how these therapies alter clearance. General

dosing considerations for continuous KRT include:

For most medications, loading doses require no adjustment.

If a drug is normally cleared by the kidneys or is removed by other KRT modalities, continuous

KRT may significantly affect its removal.

When available, drug-specific literature should be used to determine dose and frequency to

minimize the likelihood of dosing errors. Continuous KRT may be interrupted for various reasons,

and if held for an extended time or beyond scheduled medication dosing frequencies, medication

dose adjustments may be required.

can more readily clear small and middle MW molecules, and flow rates are higher than previously

used. Collectively, these aspects would be expected to increase drug clearance and make historically

recommended doses insufficient when applied to modern practice.

With the many variables associated with continuous KRT delivery (e.g., modality, dialyzers,

circuit downtime, patient instability), therapeutic drug monitoring should be used, when available,

especially for drugs with a narrow therapeutic index.

drug elimination), and drug properties influence medication elimination. Effluent is any fluid leaving the

circuit and not returned to the patient. This is spent fluid and could be dialysate or an ultrafiltrate from

the blood.

Drug proprieties that influence removal during continuous KRT include protein binding, molecular

weight (MW), and volume of distribution (Vd). Drug charge (Gibbs-Donnan effect) is less important.

The ability of a drug to bind to plasma protein (i.e., albumin) greatly influences how it is removed by

continuous KRT. Removal is inversely proportional to the percent bound (i.e., the higher the percent

bound, the less removed). Protein binding affects removal for both convection and diffusion.