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 ( CL T otal ), CL by CVVH ( CL HF ), 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 CL HF was 3.27 ± 0.48 L/hour, which accounted for 23 ± 4% of the CL T otal (14.74 ± 4.75 L/hr). Cilastatin CL HF was 1.98 ± 0.56 L/hour, which accounted for 45 ± 19% of the CL T otal (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.