In this episode, I’ll discuss an article about enhanced renal clearance in patients with hemorrhagic stroke.
Lead author: Kathryn Morbitzer
Published in Critical Care Medicine March 2019
Augmented or enhanced renal clearance is a phenomenon in some critically ill patients whereby their kidney function becomes supranormal. Awareness of clinicians to the possibility of augmented renal clearance in critically ill patients is growing. Augmented renal clearance is well-documented in trauma patients, especially those under the age of 50. The authors of this study sought to evaluate augmented renal clearance over time in patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage.
The study was of a prospective, observational design and took place in a neurosciences ICU in a tertiary care academic medical center. Patients had an admission diagnosis of aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage. To detect augmented or enhanced renal clearance the authors measured creatinine clearance via 8-hour urine collection and compared this measured creatinine clearance to creatinine clearance calculated by the Cockcroft-Gault equation and estimated glomerular filtration rate calculated by the Modification of Diet in Renal Diseases equation.
Important inclusion criteria was that patients had no evidence of renal dysfunction (admission serum creatinine < 1.5 mg/dL), and no history of chronic kidney disease.
Enhanced renal clearance was defined as a measured creatinine clearance greater than the calculated creatinine clearance via Cockcroft-Gault and estimated glomerular filtration rate via Modification of Diet in Renal Disease. Augmented renal clearance was defined by a measured creatinine clearance greater than or equal to 130 mL/min/1.73 m2.
A total of 80 patients were enrolled, 50 with aneurysmal subarachnoid hemorrhage patients and 30 with intracerebral hemorrhage. Patients with aneurysmal subarachnoid hemorrhage had significantly higher mean measured creatinine clearance compared with the Cockcroft-Gault equation and Modification of Diet in Renal Disease equation.
All but 3 of the patients with aneurysmal subarachnoid hemorrhage experienced augmented renal clearance on at least 1 day in the ICU.
In patients with intracerebral hemorrhage, there also was a higher mean measured creatinine clearance via Cockcroft-Gault equation and Modification of Diet in Renal Disease equation.
Half of the patients with intracerebral hemorrhage experienced augmented renal clearance on at least 1 day in the ICU.
The authors concluded:
A substantial group of patients with aneurysmal subarachnoid hemorrhage or intracerebral hemorrhage experienced enhanced renal clearance, which may be otherwise unknown to clinicians. Enhanced renal clearance may lead to increased renal solute elimination over what is expected, resulting in subtherapeutic renally eliminated drug concentrations. This may result in underexposure to critical medications, leading to treatment failure and other medical complications.
A significant difference between this study and that of others examining augmented renal clearance is the age of the study participants. The mean age in the SAH group was 57 years, and the mean age in the ICH group was 70 years. This greatly expands the universe of patients who could possibly develop augmented renal clearance. A previously published weighted scoring system for augmented renal clearance will only output a positive score in patients less than 50 years of age. You can use a calculator for this scoring system at pharmacyjoe.com/arc.
The primary class of medications that are of concern in critically ill patients with augmented renal clearance are antibiotics.
Antibiotic dose recommendations are based on pharmacodynamic dose-finding studies in patients with ARC and generally involve using higher doses and extended infusions such as:
– Piperacillin-tazobactam 4.5 g over 4 hours every 6 hours
– Meropenem 2 g over 3 hours every 8 hours
– Cefepime 2 g over 3 hours every 6 hours
For antibiotics that allow therapeutic drug monitoring such as vancomycin and aminoglycosides, the recommended dosing is at the high end of usual dose ranges (vanco 25–30mg/kg loading dose, then 15–20 mg/kg every 8–12 hrs or gentamicin 7mg/kg/day) with adjustments as drug levels require.
With the finding of augmented renal clearance in neurocritical patients, an additional medication of concern may be levetiracetam, although there are no specific recommendations on how to adjust levetiracetam dosing in the setting of augmented renal clearance.
A detailed, practical review of augmented renal clearance is available to members of my Hospital Pharmacy Academy. To get immediate access to this and many more resources to help you in your practice go to pharmacyjoe.com/academy.
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