Meropenem Dosing in CRRT
For critically ill patients on CRRT, administer meropenem 1 gram every 8 hours as a 3-hour extended infusion, with dose adjustments based on residual diuresis and pathogen MIC. 1, 2
Standard Dosing Approach
Initial Dosing for Most CRRT Patients
- Start with 1 gram every 8 hours infused over 3 hours for patients with oligoanuria (minimal residual urine output) 3
- This regimen achieves adequate pharmacodynamic targets (40% time above MIC) for susceptible organisms with MIC ≤2 mg/L 2, 3
- The 3-hour extended infusion is superior to 30-minute bolus dosing for optimizing time-dependent killing of beta-lactams 4, 1
Impact of Residual Diuresis
- Residual diuresis is the most important clinical parameter affecting meropenem clearance, more so than CRRT intensity 2
- Patients with preserved diuresis (>500 mL/24h) have significantly higher clearance and require more aggressive dosing 2
- For patients with residual diuresis >500 mL/24h treating organisms with MIC 2-4 mg/L: increase to 500 mg every 6 hours as 3-hour infusion 2
- CRRT dose (25-50 mL/kg/h) has minimal clinical impact on meropenem clearance 3
Alternative Dosing Strategies
Continuous Infusion Protocol
- Loading dose: 500 mg IV over 30 minutes, followed by 2-4 grams per 24 hours as continuous infusion 3, 5
- Achieves steady-state concentrations of 18-24 mg/L, maintaining consistent drug levels above MIC 5
- Particularly useful for organisms with MIC ≤0.5 mg/L in non-trauma patients 3
- Comparable AUC to intermittent dosing (227 vs 233 mg/L*h) but with more stable concentrations 5
Trauma Patients Require Special Consideration
- Trauma patients have dramatically higher volume of distribution (69.5 L vs 15.7 L in septic patients) and increased clearance 6, 3
- For trauma patients on CRRT: 3-4 grams per 24 hours as continuous infusion for organisms with MIC ≤0.5 mg/L 3
- Avoid meropenem in trauma patients for organisms with MIC ≥8 mg/L, as required doses become excessive 6
High MIC Organisms (≥8 mg/L)
When Treating Resistant Pathogens
- Administer 2 grams every 8 hours as 3-hour extended infusion for organisms with MIC ≥8 mg/L 1
- Target 100% time above MIC rather than standard 40% target for resistant organisms 2, 3
- Consider meropenem-vaborbactam or alternative agents for carbapenem-resistant organisms 1
- Meropenem monotherapy may be inadequate for MIC ≥8 mg/L in polytrauma patients even with dose escalation 6
Therapeutic Drug Monitoring
When and What to Monitor
- Perform TDM at 24-48 hours after treatment initiation and after any dosing changes 4, 1
- For intermittent dosing: measure trough concentrations (target >4-8 mg/L for MIC 2 mg/L) 4
- For continuous infusion: measure steady-state concentrations (target 4-5 times the MIC) 1
- Repeat TDM with significant changes in clinical status, fluid balance, or residual renal function 4, 1
Avoiding Toxicity
- Monitor for trough concentrations >45 mg/L, which increase seizure risk 3
- Risk of toxicity is low with standard dosing but increases with continuous high-dose infusions 3
Pharmacokinetic Considerations
Key PK Parameters in CRRT
- Half-life extends from 1 hour (healthy volunteers) to 5-7 hours in CRRT patients 7, 5
- CRRT removes 13-53% of meropenem depending on modality (CVVHDF removes more than CVVHF) 7
- Peak concentrations after 1 gram IV range 18-45 mg/L in CRRT patients vs 53-62 mg/L in healthy volunteers 7
- Total body clearance averages 3.7 L/h in oligoanuric patients, increasing by 0.22 L/h per 100 mL residual diuresis 2
Common Pitfall to Avoid
- Do not rely solely on CRRT prescription to guide dosing—the actual delivered CRRT dose often differs from prescribed, and residual renal function is more clinically relevant 2, 3
- Underdosing is the primary risk given meropenem's excellent tolerability profile 7
- Reassess if clinical response is inadequate after 48-72 hours despite adequate source control 1