Meropenem Removal by CRRT
Approximately 25-50% of meropenem is removed by continuous renal replacement therapy, with significant variation depending on the specific CRRT modality used. 1
Removal Rates by CRRT Modality
The extent of meropenem removal varies substantially based on the type of CRRT:
CVVH (Continuous Venovenous Hemofiltration): Removes 25-50% of meropenem, with studies showing approximately 47% of the administered dose eliminated through hemofiltration 1, 2
CVVHDF (Continuous Venovenous Hemodiafiltration): Removes 13-53% of meropenem, demonstrating the widest variability among modalities 1
Hemofiltration clearance: Contributes approximately 22.0 ± 4.7 mL/min to total drug clearance, representing a substantial portion of overall elimination 2
Pharmacokinetic Impact of CRRT
The removal of meropenem by CRRT significantly alters its pharmacokinetic profile:
Half-life extension: Meropenem's half-life increases from approximately 1 hour in healthy volunteers to 5.3-8.7 hours in critically ill patients receiving CRRT 2, 3
Total body clearance: Ranges from 52.0 ± 8.4 mL/min in anuric patients on CVVH, with hemofiltration accounting for nearly half of this clearance 2
Volume of distribution: Approximately 12.4-15.7 L in septic patients, though this can increase substantially to 69.5 L in polytraumatized patients 4, 2
Critical Dosing Implications
Because hemofiltration contributes significantly to meropenem elimination, standard doses must be increased to avoid underdosing in patients receiving CRRT. 2
Key Dosing Considerations:
Residual diuresis matters more than CRRT intensity: Preserved residual kidney function (not CRRT flow rate) was identified as the primary modifier of meropenem clearance, with clearance increasing by 0.22 L/h for every 100 mL of residual diuresis per 24 hours 5
Extended infusion is recommended: The French Society of Pharmacology and Therapeutics recommends extended or continuous infusion of beta-lactams in critically ill patients to optimize pharmacodynamic targets 6
Therapeutic drug monitoring is essential: TDM should be performed in ICU patients undergoing renal replacement therapy due to considerable PK changes caused by CRRT 6
Common Pitfall to Avoid
The most critical error is assuming CRRT intensity (dialysate/ultrafiltrate flow rate) is the primary determinant of meropenem dosing requirements. CRRT intensity was NOT identified as a significant clearance modifier in population pharmacokinetic studies 5. Instead, residual diuresis is the key clinical parameter that should guide dose adjustments, making it an easy and inexpensive tool for dose titration 5.