Pharmacokinetics of meropenem in intensive care patients receiving continuous renal replacement therapy

Introduction

This study was conducted to determine the appropriate dose of meropenem in critically ill patients with acute renal failure treated by continuous veno-venous haemofiltration (CVVH) or haemodiafiltration (CVVHDF) who require this antibiotic therapy.

Methods

Ten critically ill patients (7m, 3f, mean age 65 years (range: 51–77 years), mean weight 80 kg (range: 51–119 kg), mean APACHE II 27.7 (range: 21-37) were included. All patients were receiving CVVH (n = 5) (haemofiltration rate 1–2 l/h) or CVVHDF (n = 5) (haemofiltration rate 1–1.5 l/h: dialysis rate 1–1.5 l/h) using a polyacrylonitrile (AN69) hollow fibre 0.9 m² filter (Multiflow 100, Hospal). All patients received a meropenem dose of 1 g 12 hourly, intravenously over 5 min. Venous serum samples were taken pre-dose and 5, 15, 30, 60, 90, 120, 240, 360, 480 min post-dose on day 3 to approximate steady state conditions. Haemofiltrate was collected for determination of a sieving coefficient. Samples were analysed by high performance liquid chromatography.

Results

Sieving coefficient for meropenem with the AN69 filter was 0.93 ± 0.06 (n = 9) indicating free flow across the membrane. Mean (± SD) serum concentrations at pre-dose, 5, 15, 30, 60, 90, 120, 240, 360, 480 mins post-dose were: 7.6 (5.1), 90.9 (23.9), 66.0 (13.0), 53.9 (15.7), 40.0 (10.3), 39.0 (9.2), 31.0 (10.4), 21.1 (6.9), 17.2 (6.2), 13.8 (6.4) mg/l respectively. Actual pre-dose (C_trough), 5 min (C_peak) and 480 min levels are given below. Serum concentrations remained above the MIC₉₀ for Ps. aeruginosa (4 mg/l) in all patients for two-thirds of the dosage interval which is the target recommended for β-lactam antibiotics. A lower dose may not have been sufficient for all the patients.

Conclusion

A meropenem dose of 1 g 12 hourly is adequate in patients treated with CVVH or CVVHDF using an AN69 HF 0.9 m² filter.

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