What is the estimated creatinine clearance for dosing medication in a patient on Continuous Renal Replacement Therapy (CRRT)?

Estimated Creatinine Clearance for Medication Dosing in Patients on CRRT

For medication dosing in patients receiving continuous renal replacement therapy (CRRT), use an estimated creatinine clearance of 10-15 mL/min as the baseline assumption, then add the effluent flow rate (QE) to calculate total drug clearance. 1, 2

Practical Dosing Framework

Step 1: Establish Baseline Nonrenal Clearance

• Assume the patient's residual renal clearance is negligible (effectively zero) when on CRRT 2
• Use a creatinine clearance equivalent of 10-15 mL/min to represent the patient's nonrenal (hepatic and other) clearance pathways 1
• This baseline reflects the systemic clearance observed in patients with creatinine clearance <15 mL/min who are not yet on dialysis 2

Step 2: Add CRRT-Specific Clearance

• Calculate extracorporeal clearance (CLCRRT) as: free fraction (fu) × effluent flow rate (QE) 2
• For most low-molecular-weight drugs (similar to cefiderocol at 752 Da), the free fraction is completely filtered regardless of CRRT modality 2
• Total drug clearance = nonrenal clearance (10-15 mL/min equivalent) + (fu × QE) 2

Step 3: Match to Standard Dosing Categories

For practical medication dosing adjustments, patients on CRRT typically fall into these categories:

• Low-intensity CRRT (QE <10 mL/kg/h): Dose as CrCl <15 mL/min 1
• Standard-intensity CRRT (QE 15-25 mL/kg/h): Dose as CrCl 15-30 mL/min 1
• High-intensity CRRT (QE >25 mL/kg/h): Dose as CrCl 30-50 mL/min 1

Critical Considerations

Why Not Use Serum Creatinine Alone

• Serum creatinine is unreliable during CRRT because it reflects both residual renal function (minimal) and CRRT clearance, creating an artificial steady state 1
• Using a Cr cutoff of 1.5 mg/dL fails to identify 40% of patients at risk for drug accumulation 3
• Creatinine clearance calculations (Cockcroft-Gault or Mawer equations) are invalid during active CRRT because they assume stable renal function, which does not exist 4

Drug-Specific Adjustments

• For renally eliminated drugs: Use the total clearance calculation (baseline + CRRT clearance) 2
• For hepatically metabolized drugs: Minimal adjustment needed beyond baseline nonrenal clearance 2
• For drugs with narrow therapeutic windows (vancomycin, aminoglycosides): Therapeutic drug monitoring is essential regardless of calculated clearance 5

Common Pitfalls to Avoid

• Do not use standard CrCl estimation formulas (Cockcroft-Gault, MDRD) during active CRRT—these overestimate actual clearance 4
• Do not assume CRRT provides consistent clearance—interruptions for procedures, filter clotting, and downtime reduce effective clearance 1
• Do not ignore effluent flow rate changes—increasing QE from 15 to 25 mL/kg/h significantly increases drug clearance 1, 2
• Do not dose based on pre-CRRT creatinine values—these become irrelevant once CRRT begins 1

Monitoring Strategy

• Measure trough levels for drugs with established therapeutic ranges (vancomycin target trough 15-20 mg/L for serious infections) 5
• Reassess dosing if CRRT intensity changes by more than 5 mL/kg/h 2
• Consider supplemental dosing after filter changes for highly protein-bound drugs that may adsorb to new filters 2

Practical Example: Vancomycin Dosing

• Loading dose: 25-30 mg/kg (regardless of CRRT) to achieve rapid therapeutic levels 5
• Maintenance dosing on standard CRRT (20-25 mL/kg/h):
  • Dose as CrCl 15-30 mL/min: approximately 1 gram every 48 hours 5
  • Adjust based on trough levels measured 30 minutes before next dose 5
• For high-intensity CRRT (>25 mL/kg/h): May require 1 gram every 24-36 hours 5

1, 2