Ensure proper medication dosing. Understand drug removal by dialysis on CRRT.
Very sick patient is admitted to the intensive care unit with sepsis. The patient is in septic shock and antibiotics including vancomycin and pressors are started. The creatinine rises, the urine output decreases, and the patient is diagnosed with AKI. The critical care provider starts hydrocortisone.
Nephrology is consulted to consider starting slow dialysis, CRRT.
CRRT
Paying attention to drug removal by dialysis is important.
The team wants to start total parenteral nutrition as well.
The nephrologist meets with the pharmacist to discuss TPN and drug removal by dialysis.
The determinants of drug removal by dialysis, during CRRT are drug-related (molecular weight, degree of protein binding, volume of distribution) and CRRT-related.
Higher effluent rates do correlate with increased drug clearance. Therefore, for therapeutic dosing in CRRT, some medications may need to be dosed higher to achieve a therapeutic effect.
Medications that are greater than 15,000 Da are not significantly cleared by standard high-flux membranes in any continuous renal replacement modality.
Discussion
Continuous Renal Replacement Therapy (CRRT) and Drug Removal by Dialysis
Overview of CRRT in End-Stage Kidney Disease
Patients with end-stage kidney disease (ESKD) undergoing continuous renal replacement therapy (CRRT) require careful medication management. This includes a thorough review of all medications and total parenteral nutrition (TPN) to ensure appropriate dosing.
CRRT can significantly remove certain medications, making it crucial to understand the factors influencing drug removal to maintain therapeutic drug levels and avoid subtherapeutic effects.
Determinants of Drug Removal by Dialysis
The removal of drugs during dialysis, CRRT, is influenced by both drug-related and CRRT-related factors.
Drug-related factors: Molecular weight Degree of protein binding Volume of distribution (Vd)
CRRT-related factors: Dialyzer characteristics (permeability and charge) Type of convective or diffusive modality used Pre-filter replacement fluid Effluent rates Residual kidney function
Impact of Dialyzer Characteristics Dialyzer characteristics play a significant role in drug clearance. Convective modalities clear larger drugs more effectively than diffusive modalities. Pre-filter replacement fluid can decrease drug clearance by diluting the drug concentration in the dialyzer. Higher effluent rates correlate with increased drug clearance.
Drug Size and Clearance The size of the drug is a critical factor in determining its clearance during CRRT: Drugs with a molecular weight <2000 Da are effectively removed by CVVH, CVVHD, and CVVHDF. Drugs >5000 Da are better cleared by convective modalities compared to diffusive modalities. Drugs >15,000 Da show minimal clearance with standard high-flux membranes in any CRRT modality.
Protein Binding and Volume of Distribution Only unbound drugs are removed by CRRT, which means: Highly protein-bound medications are poorly cleared. Drugs confined to the vascular compartment have a smaller volume of distribution (Vd) and are removed more efficiently. Drugs with a Vd > 2 L/kg are poorly removed because of greater extravascular distribution and tissue binding.
Conclusion
Understanding the factors that influence drug removal during CRRT is essential for optimizing medication dosing in patients with end-stage kidney disease. This includes considering drug characteristics, CRRT modalities, and patient-specific factors, such as residual renal function.
