Can Piperacillin Dose Be Predicted by Renal Function in Intensive Care Unit Patients? Comparison of 3 Different...

Area of Science:

• Pharmacokinetics and Pharmacodynamics
• Critical Care Medicine
• Nephrology

Background:

• Augmented renal clearance in intensive care unit (ICU) patients is linked to piperacillin underexposure.
• Optimal piperacillin dosing strategies based on renal function in ICU settings remain unclear.
• Previous studies indicate a risk of inadequate piperacillin levels in critically ill patients.

Purpose of the Study:

• To evaluate the predictability of piperacillin underexposure and overexposure using different renal function formulas.
• To assess the adequacy of a standard piperacillin regimen in ICU patients with varying renal function.
• To determine theoretical piperacillin doses required for therapeutic concentrations across different renal clearance groups.

Main Methods:

• Retrospective analysis of piperacillin steady-state concentrations (Css) in 159 ICU patients receiving continuous infusion.
• Estimation of renal function using Cockcroft-Gault, MDRD, and CKD-EPI 2021 formulas.
• Receiver operating characteristic (ROC) curve analysis to assess the association between renal function formulas and piperacillin exposure.

Main Results:

• Cockcroft-Gault equation was a slightly better predictor of piperacillin underexposure (cutoff 128 mL/min) and overexposure (cutoff 81 mL/min).
• Piperacillin underexposure increased from 23% to 88% as creatinine clearance rose from 60-90 mL/min to >160 mL/min.
• Theoretical daily piperacillin dose increased significantly with renal function, but with substantial interindividual variability.

Conclusions:

• Progressive increases in daily piperacillin dosage are supported by renal function.
• Significant interindividual variability in piperacillin pharmacokinetics prevents robust a priori dosing recommendations.
• Therapeutic drug monitoring is essential for optimizing piperacillin therapy in ICU patients.