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Discrepancies between observed and predicted continuous venovenous hemofiltration removal of antimicrobial agents in critically ill patients and the effects on dosing

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Abstract

Objective

Drug dosing during continuous venovenous hemofiltration (CVVH) is based partly upon the CVVH clearance (ClCVVH) of the drug. ClCVVH is the product of the sieving coefficient (SC) and ultrafiltration rate (Quf). Although it has been suggested that the SC can be replaced by the fraction of a drug not bound to protein (Fup), the Fup values as reported in the literature may not reflect the protein binding in critically ill patients with renal failure. We compared the observed ClCVVH (SC × Quf) with the estimated ClCVVH (estimated FUP × Quf) and determined the effect on the maintenance dose multiplication factor (MDMF).

Design and setting

Clinical study in a mixed ICU in a university hospital.

Patients

45 oligoanuric patients on CVVH (2 l/h).

Interventions

Timed blood and ultrafiltrate samples.

Measurements and results

Amoxicillin, ceftazidime, ciprofloxacin, fluconazole, metronidazole, and vancomycin were easily filtered (mean SC > 0.7) but not flucloxacillin (mean SC 0.3). Predicted and observed ClCVVH corresponded only for fluconazole and metronidazole. The difference between observed and predicted MDMF was small for all drugs, with the exception of ceftazidime (mean 0.25, 95% CI −0.96 to 1.48) and vancomycin (0.05, −1.34 to 1.45). However, this difference was clinically relevant only for vancomycin, because of its narrow therapeutic index.

Conclusions

Dosing based on predicted CVVH removal provides an as reliable estimate than that based on observed CVVH removal except for those antibiotics that have both a narrow therapeutic index and a predominantly renal clearance (e.g., vancomycin).

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Authors and Affiliations

  1. Department of Intensive Care, Academic Medical Center, University of Amsterdam, 1100 DD, 22660, Amsterdam, Netherlands

    Catherine S. C. Bouman, Marcus J. Schultz & Margreeth B. Vroom

  2. Department of Clinical Pharmacy, Academic Medical Center, University of Amsterdam, 1100 DD, 22660, Amsterdam, Netherlands

    Hendrikus J. M. van Kan

  3. Department of Internal Medicine, Academic Medical Center, University of Amsterdam, 1100 DD, 22660, Amsterdam, Netherlands

    Richard P. Koopmans

  4. Department of Epidemiology, Academic Medical Center, University of Amsterdam, 1100 DD, 22660, Amsterdam, Netherlands

    Johanna C. Korevaar

  5. Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, 1100 DD, 22660, Amsterdam, Netherlands

    Marcus J. Schultz

Authors
  1. Catherine S. C. Bouman
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  2. Hendrikus J. M. van Kan
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  3. Richard P. Koopmans
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  4. Johanna C. Korevaar
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  5. Marcus J. Schultz
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  6. Margreeth B. Vroom
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Corresponding author

Correspondence to Catherine S. C. Bouman.

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Bouman, C.S.C., van Kan, H.J.M., Koopmans, R.P. et al. Discrepancies between observed and predicted continuous venovenous hemofiltration removal of antimicrobial agents in critically ill patients and the effects on dosing. Intensive Care Med 32, 2013–2019 (2006). https://doi.org/10.1007/s00134-006-0397-x

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  • DOI: https://doi.org/10.1007/s00134-006-0397-x

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