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    A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics

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    Author
    Roberts, DM; Liu, X; Roberts, JA; Nair, P; Cole, L; Roberts, MS; Lipman, J; Bellomo, R
    Date
    2015-03-13
    Source Title
    Critical Care (UK)
    Publisher
    BIOMED CENTRAL LTD
    University of Melbourne Author/s
    Bellomo, Rinaldo
    Affiliation
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    Roberts, D. M., Liu, X., Roberts, J. A., Nair, P., Cole, L., Roberts, M. S., Lipman, J. & Bellomo, R. (2015). A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics. CRITICAL CARE, 19 (1), https://doi.org/10.1186/s13054-015-0818-8.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/258034
    DOI
    10.1186/s13054-015-0818-8
    Abstract
    INTRODUCTION: Continuous renal replacement therapy (CRRT) may alter antibiotic pharmacokinetics and increase the risk of incorrect dosing. In a nested cohort within a large randomized controlled trial, we assessed the effect of higher (40 mL/kg per hour) and lower (25 mL/kg per hour) intensity CRRT on antibiotic pharmacokinetics. METHODS: We collected serial blood samples to measure ciprofloxacin, meropenem, piperacillin-tazobactam, and vancomycin levels. We calculated extracorporeal clearance (CL), systemic CL, and volume of distribution (Vd) by non-linear mixed-effects modelling. We assessed the influence of CRRT intensity and other patient factors on antibiotic pharmacokinetics. RESULTS: We studied 24 patients who provided 179 pairs of samples. Extracorporeal CL increased with higher-intensity CRRT but the increase was significant for vancomycin only (mean 28 versus 22 mL/minute; P = 0.0003). At any given prescribed CRRT effluent rate, extracorporeal CL of individual antibiotics varied widely, and the effluent-to-plasma concentration ratio decreased with increasing effluent flow. Overall, systemic CL varied to a greater extent than Vd, particularly for meropenem, piperacillin, and tazobactam, and large intra-individual differences were also observed. CRRT dose did not influence overall (systemic) CL, Vd, or half-life. The proportion of systemic CL due to CRRT varied widely and was high in some cases. CONCLUSIONS: In patients receiving CRRT, there is great variability in antibiotic pharmacokinetics, which complicates an empiric approach to dosing and suggests the need for therapeutic drug monitoring. More research is required to investigate the apparent relative decrease in clearance at higher CRRT effluent rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT00221013. Registered 14 September 2005.

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