Chapter 112: Medication Dosing During Renal Replacement Therapy

The aim of drug dosing is to maintain pharmacokinetics (a similar peak, trough, or average steady-state drug concentration) to achieve a desired pharmacodynamic response without adverse side effects.¹ In critically ill patients receiving renal replacement therapy (RRT), however, determining appropriate drug dosing is challenging because pharmacodynamic target attainment is determined by a complex interplay between drug dosing, pharmacokinetic changes within the critically ill patient, and the type of RRT selected (Table 112–1).² A stepwise approach for patients with chronic kidney disease and acute kidney injury has been proposed (Table 112–2).³ For assessment of kidney function, estimation by equation is generally more accurate than measured creatinine clearance, given errors in urine collection.⁴ Therefore, the National Kidney Disease Education Program in the United States recommends estimation of the glomerular filtration rate from the Cockcroft and Gault equation for adults: urinary creatinine clearance = (140 – age [years]) × weight (kg) × 0.85 (for female)/serum creatinine (mg/dL) × 72 or the Schwartz equation for children.^5,6

Table 112–3 contains guidelines by the American College of Physicians for drug dosing in renal failure requiring RRT.⁷ There are a variety of RRTs including hemodialysis, continuous RRT, and peritoneal dialysis. When applying these or other guidelines it should be understood that dosing recommendations for one form of RRT usually cannot be applied to other forms of RRT.⁸ Dialysis filter type, surface area; the blood, dialysate, and ultrafiltration rates; and interruptions due to circuit clotting influence drug clearance and affect drug dosing.

Drug dosing studies in renal failure have not been conducted in most marketed drugs.^8,9 In addition, the evidence level is weak as most of these studies are small and also the dose of RRT is not uniform. Finally, technological advances in RRT over the last several years have resulted in greater drug clearances; consequently, drug dosing recommendations may be outdated. Therefore, the most effective dosing optimization strategy is to estimate renal function and begin dosing according to the guidelines, followed by closely monitoring drug levels (if possible) or the clinical response, and adjusting the dosing accordingly (Table 112–2).

Table 112–1 Factors to alter pharmacodynamics of critically ill patients.²