Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration

STUDY OBJECTIVE High-dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high-dose CVVH. DESIGN Prospective clinical pharmacokinetic study. PATIENTS Ten adult patients with burns receiving I/C for a documented infection and requiring high-dose CVVH were studied. METHODS Blood and effluent samples for analysis of I/C concentrations were collected for up to 6 hours after the I/C infusion for calculation of I/C total CL (CLTotal), CL by CVVH (CLHF), half-life during CVVH, volume of distribution at steady state (Vd(ss)), and the percentage of drug eliminated by CVVH. RESULTS In this patient sample, the mean age was 50 +/- 17 years, total body surface area burns was 23 +/- 27%, and 80% were male. Nine patients were treated with high-dose CVVH for acute kidney injury and one patient for sepsis. The mean delivered CVVH dose was 52 +/- 14 ml/kg/hour (range 32-74 ml/kg/hr). The imipenem CLHF was 3.27 +/- 0.48 L/hour, which accounted for 23 +/- 4% of the CLTotal (14.74 +/- 4.75 L/hr). Cilastatin CLHF was 1.98 +/- 0.56 L/hour, which accounted for 45 +/- 19% of the CLTotal (5.16 + 2.44 L/hr). The imipenem and cilastatin half-lives were 1.77 +/- 0.38 hours and 4.21 +/- 2.31 hours, respectively. Imipenem and cilastatin Vd(ss) were 35.1 +/- 10.3 and 32.8 +/- 13.8 L, respectively. CONCLUSION Efficient removal of I/C by high-dose CVVH, a high overall clearance, and a high volume of distribution in burn intensive care unit patients undergoing this CRRT method warrant aggressive dosing to treat serious infections effectively depending on the infection site and/or pathogen.