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Chapter 112: Medication Dosing During Renal Replacement Therapy

Jun Makino; John M. Oropello

INTRODUCTION

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 112–1Factors to alter pharmacodynamics of critically ill patients.2
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Table 112–1 Factors to alter pharmacodynamics of critically ill patients.2
Factors Pharmacokinetic Change Response to Change
Fluid overload Increased volume of distribution Give a larger loading dose
Increased capillary permeability Increased volume of distribution Give a larger loading dose
Hypoalbuminemia Increased drug availability to exert pharmacologic effect or increased drug elimination Potential dosage adjustment for highly protein-bound drugs
Augmented renal clearance Increased drug elimination More frequent dosing interval
AKI Decreased drug elimination Adjust doses on drugs eliminated by the kidney
AKI requiring RRT Increased drug elimination Dose adjust as RRT modality chosen
Preserved nonrenal clearance in AKI Preserved drug elimination in face of AKI in selected drugs More frequent dosing interval
Increased cardiac output Increased drug elimination More frequent dosing interval
Impaired GI motility/reduced GI blood flow Decreased oral drug absorption Avoid oral medication

AKI, acute kidney injury; GI, gastrointestinal; RRT, renal replacement therapy.

Reproduced with permission from Scoville BA, Mueller BA: Medication dosing in critically ill patients with acute kidney injury treated with renal replacement therapy, Am J Kidney Dis. 2013 Mar;61(3):490-500.

Table 112–2Stepwise approach to adjust drug dosage regimens for patients with CKD and AKI.3
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Table 112–2 Stepwise approach to adjust drug dosage regimens for patients with CKD and AKI.3
Step1 Obtain history and relevant demographic/clinical information Assess demographic information, past medical history, current clinical, and laboratory data.
Step 2 Estimate GFR Use most appropriate tools based on age, body size, ethnicity, and concomitant disease status.
Step 3 Review current medications Is it really necessary or not?
Step 4 Calculate individualized treatment regimen Calculate dosage regimen based on pharmacokinetic characteristics of the drug and the patient’s volume status and eGFR or CLcr.
Step 5 Monitor Monitor ...

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