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The Impact of Capping Creatinine Clearance on Achieving Therapeutic Vancomycin Concentrations in Neurocritically Ill Patients with Traumatic Brain Injury

Abstract

Background

Traumatic brain injury (TBI) is associated with secondary complications, including infection, and patients with TBI often exhibit augmented renal clearance (ARC). This phenomenon has been associated with subtherapeutic levels of renally cleared drugs such as vancomycin, which is dosed based on body weight and creatinine clearance (CrCl). Many clinicians, however, cap CrCl at 120 mL/min/1.73 m2 when calculating vancomycin dosing regimens. We hypothesize that capping patient CrCl, as opposed to utilizing the non-capped CrCl, when determining vancomycin dosing schemes results in subtherapeutic serum trough concentrations in patients with TBI.

Methods

This was a retrospective study of adult patients with TBI admitted between April 2014 and December 2015 who received vancomycin. Population-based pharmacokinetic (PK) parameters using non-capped calculated CrCl and capped CrCl were compared with patient-specific PK parameters based on serum trough concentrations.

Results

Thirty-two patients with TBI were included in the study. ARC was suspected in 24 (75%) patients due to a median estimated CrCl at serum trough concentration of 167.3 (127.7–197.7) mL/min. The mean dosing regimen was 17.1 (13.2–19.2) mg/kg every 8 (8–8) h. There was no difference between the median measured trough concentration and predicted value using non-capped CrCl [10.4 (7.1–15.0) vs. 11.5 (7.8–13.7) mcg/mL; p = 0.7986]. The median measured trough concentration was significantly lower than the predicted trough concentration when calculated based on capping the CrCl at 120 mL/min/1.73 m2 [16.3 (15.3–22.0) vs. 11.5 (7.8–13.7) mcg/mL; p < 0.0001].

Conclusions

Patients with traumatic brain injury appeared to exhibit augmented renal clearance, leading to subtherapeutic vancomycin serum trough concentrations when doses were calculated using the traditional method of capping creatinine clearance at 120 mL/min/1.73 m2. Instead, utilizing patients’ non-capped creatinine clearance when determining a vancomycin dosing regimen is more accurate and provides a better estimation of vancomycin pharmacokinetics and could be applied to other renally excreted medications.

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Funding

No sources of support were provided for this research.

Author information

All authors provided substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; and final approval of the version to be published.

Correspondence to Denise H. Rhoney.

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Funding

No funding was received to carry out this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

This study received ethic approval by the Institutional Review Board at the University of North Carolina at Chapel Hill. This is included within the Methods and Materials section of the manuscript.

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Nelson, N.R., Morbitzer, K.A., Jordan, J.D. et al. The Impact of Capping Creatinine Clearance on Achieving Therapeutic Vancomycin Concentrations in Neurocritically Ill Patients with Traumatic Brain Injury. Neurocrit Care 30, 126–131 (2019). https://doi.org/10.1007/s12028-018-0583-z

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Keywords

  • Vancomycin
  • Creatinine clearance
  • Pharmacokinetics
  • Traumatic brain injury
  • Infection