Pharmacokinetics of meropenem during continuous renal replacement therapy in critically ill patients

Introduction

Antibiotic dosing for patients with acute renal failure receiving continuous renal replacement therapy (CRRT) is a clinical challenge. The aim of this study was to investigate the pharmacokinetics of meropenem (M) during CRRT.

Methods

A prospective and multicenter study was conducted at seven hospitals. Fifteen critically ill patients undergoing either continuous venovenous hemofiltration (CVVHF) or hemodiafiltration (CVVHDF) were included. Serum and ultrafiltrate (UF) levels of M were determined by liquid chromatography. Blood samples were drawn 24 hours after starting CRRT at 08:00 a.m., 09:00 a.m., 10:00 a.m., 01:00 p.m., 06:00 p.m., 20:00 p.m. and 08:00 a.m. of the following day. CRRT clearance (Cl), total amount of M in the UF (MUF), percentage of the dose extracted by CRRT (EF) and the AUC (ng/hour/ml) were calculated.

Results

Nine patients were treated with CVVHDF and six with CVVHF. M (0.5 to 2 g) was administered every 6 to 12 h by i.v. infusion over 15 minutes. Data (mean and SD) concerning the dialysate flow rate (DF; ml/hour), blood flow rate (ml/minute) and the average UF rate (ml/ kg/hour) for CRRT techniques are shown in Table 1. Pharmacokinetic parameters for M are depicted in Table 2. No differences in either EF or M Cl between the two CRRT techniques were observed.

Table 1 Parameters of CRRT techniques

Table 2 Pharmacokinetic parameters for meropenem

Conclusion

A significant removal of M by CVVHF/CVVHDF was observed. Dose adjustment is necessary in critically ill patients receiving CRRT.