Abstract
BackgroundThe majority of patients with hemorrhagic stroke experience enhanced renal clearance or augmented renal clearance (ARC). The purpose of this study was to determine the impact of enhanced renal clearance or ARC on vancomycin pharmacokinetic (PK) parameters.MethodsThis was a post hoc analysis of a prospective study of adult patients with aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH) admitted to the neurosciences intensive care unit who received vancomycin. Creatinine clearance (CrCl) was measured and also estimated using the Cockcroft-Gault equation. Predicted PK parameters were compared with calculated PK parameters using serum peak and trough concentrations.ResultsSeventeen hemorrhagic stroke patients met inclusion criteria. All patients experienced enhanced renal clearance on the day that the vancomycin concentrations were obtained, and 12 patients (71%) experienced ARC. The mean calculated elimination rate constant was significantly higher than the predicted value (0.141 ± 0.02 vs. 0.087 ± 0.01 h−1; p = 0.004) and the mean calculated half-life was significantly lower than the predicted half-life (6.5 ± 0.9 vs. 8.7 ± 0.6 h; p = 0.03).ConclusionsPatients with hemorrhagic stroke and enhanced renal clearance displayed PK alterations favoring an increased elimination of vancomycin than expected. This may result in underexposure to vancomycin, leading to treatment failure.
Highlights
Patients with hemorrhagic stroke have high disability and mortality rates [1, 2]
It has been previously reported that the vast majority of patients with hemorrhagic stroke experience a hyperdynamic state resulting in enhanced renal clearance and/or augmented renal clearance (ARC) [10, 11] to our knowledge, no studies exist examining the impact of these changes in renal clearance on renally eliminated medication pharmacokinetic parameters in this patient population
(2019) 7:51 this study was to determine whether patients experiencing enhanced renal clearance or augmented renal clearance with hemorrhagic stroke had alterations in vancomycin pharmacokinetic parameters when compared with those predicted based on population-based equations
Summary
Patients with hemorrhagic stroke have high disability and mortality rates [1, 2]. In addition to the direct effects of the initial bleeding event and secondary neurologic complications, patients with hemorrhagic stroke are predisposed to medical complications that can have a negative impact on patient outcomes and increase cost of care [3,4,5].One of the most common medical complications that occur in patients with hemorrhagic stroke is infection [3, 6]. It has been previously reported that the vast majority of patients with hemorrhagic stroke experience a hyperdynamic state resulting in enhanced renal clearance (defined as a measured CrCl greater than that calculated based on standard equations) and/or augmented renal clearance (ARC) (defined as a measured CrCl greater than or equal to 130 mL/min/1.73 m2) [10, 11] to our knowledge, no studies exist examining the impact of these changes in renal clearance on renally eliminated medication pharmacokinetic parameters in this patient population. The purpose of this study was to determine the impact of enhanced renal clearance or ARC on vancomycin pharmacokinetic (PK) parameters
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