Optimization of meropenem and piperacillin dosing during continuous renal replacement therapy (CRRT) interruption and liberation in critically ill patients: an in silico sub-study from the SMARRT Study
Authors' conclusion
Our study provides recommendations for meropenem and piperacillin during CRRT interruptions and liberation.
Study context
- Population
- Critically ill patients receiving CRRT, with interruptions or liberation, across CRRT intensities and urine outputs
- Participants
- 300 SMARRT models
- Comparison
- Meropenem and piperacillin dosing regimens during 6-h and 24-h CRRT interruptions and CRRT liberation
- Primary endpoint
- Probability of target attainment (PTA): unbound concentrations above MIC (2-8 mg/L meropenem; 16-64 mg/L piperacillin); toxicity thresholds >45 mg/L and >160 mg/L; regimens with PTA >90% and toxicity risk <15% selected
Methodological detailsin silico sub-study of the SMARRT study, validated population pharmacokinetic models
- In silico sub-study of the SMARRT study
- Validated population pharmacokinetic models
Primary result
As reported in the abstract
Dosing during 6-h interruptions
- Anuric, CRRT 1.5-2.5 L/h: maintain dose if total daily dose ≤3 g (meropenem) or ≤8 g (piperacillin)
- Anuric, CRRT >2.5 L/h: maintain dose up to 4 g (meropenem) and 12 g (piperacillin)
- With urine output (≥500 mL/24h meropenem, ≥100 mL/24h piperacillin): meropenem 4 g/24h at 1.5 - 2.5 L/h and 6 g/24h at >2.5 L/h; piperacillin 12 g/24h at 1.5-3.5 L/h
- Higher daily doses should be withheld
Further findings
CRRT liberation
- Adjust antimicrobials to therapeutic target and infusion regimen
- Continuous infusion gave best exposure, ≥90% probability of target attainment (PTA) with meropenem 1.5-3 g/24 h and piperacillin 6-8 g/24 h, reducing toxicity risk
Original publication
Optimization of meropenem and piperacillin dosing during CRRT interruption and liberation in critically ill patients: an in silico sub-study from the SMARRT Study. Anaesth Crit Care Pain Med. Published 24 September 2026. doi:10.
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