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Abstract

Introduction: Sustained low-efficiency dialysis (SLED) is an alternative to other chronic renal replacement therapy (CRRT) modalities for critically ill patients unable to tolerate intermittent hemodialysis. Limited information is available to guide vancomycin dosing during SLED in critically ill patients and this lack of information may lead to treatment failures or toxicity. Hypothesis: To determine the pharmacokinetics and clearance of vancomycin during SLED administered to critically ill ICU patients. Methods: This study was a prospective evaluation of vancomycin pharmacokinetics in patients?19 years of age, with urine output < 200 ml/day and receiving SLED for at least 8 hours. Following informed consent, plasma samples were collected at baseline and 1, 2, 4 and 8 hours after the administration of a vancomycin infusion, and post-SLED therapy at 0.5, 1, 3, 8, and 24 hours. Dialysate samples were also collected at the same intervals of plasma samples during SLED. Plasma and dialysate samples were frozen and analyzed by HPLC. Pharmacokinetic calculations were determined using WinNonlin and parameters obtained during SLED were compared to post-SLED data. Results: A total of seven patients (5 male/2 female, age 59 ± 9 years, APACHE II 27.6 ± 107) were enrolled. During SLED, vancomycin was rapidly removed with a half-life of 13.0 ± 4.9h, Ke 0.0599 1/h, and clearance 66.1 ± 22.7 ml/min compared to a half-life exceeding 150 hours and clearance < 10 ml/min while not on SLED. Following a change in dialysis technique, the latter five patients experienced an even more rapid clearance of 77.6 ± 13.9 ml/min. Conclusions: Vancomycin is rapidly cleared during SLED with an estimated clearance of 66.1 and 77.6 ml/min respectively. To prevent under dosing of vancomycin during SLED, an estimated Clcr of 75 ml/min should be used with frequent measurement of plasma concentrations.