title: Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics.
abstract: Augmented renal clearance (ARC) has been reported in approximately 30-65% of patients in the intensive care unit (ICU) despite the presence of a normal serum creatinine concentration. In certain ICU patient populations (e.g., patients with sepsis or trauma), the incidence increases to roughly 50-85%. Risk factors for ARC include the following: age younger than 50-55 years, male sex, higher diastolic blood pressure, fewer comorbidities, and a lower Acute Physiology and Chronic Health Evaluation II (APACHE II) or modified Sequential Organ Failure Assessment (SOFA) score at ICU admission. In addition, patient populations with the highest reported incidence of ARC include those with major trauma, sepsis, traumatic brain injury, subarachnoid hemorrhage, and central nervous system infection. Due to the high incidence of ARC in patients with a normal serum creatinine concentration, clinicians should consider screening ICU patients deemed high risk by using the ARC scoring system or the identification and assessment algorithm provided in this review. In addition, an 8-hour continuous urine collection should be considered to assess a measured creatinine clearance for evaluating the necessity of medication dosage adjustments. There is a clear association between ARC and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with ARC could increase the risk of treatment failure. This review examines strategies to overcome ARC and summarizes current pharmacokinetic and pharmacodynamic literature in patients with ARC in an effort to provide dosing guidance for this patient population.
authors.affiliation: Department of Pharmacy, Baptist Memorial Hospital - Memphis, Memphis, Tennessee.
authors.forename: Athena L V
authors.initials: AL
authors.lastname: Hobbs
authors.affiliation: Innovative Delivery Solutions, Cardinal Health, Houston, Texas.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Shea
authors.affiliation: Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Roberts
authors.affiliation: Department of Pharmacy, Seton Healthcare Family, Austin, Texas.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Daley
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003404:Creatinine / Q000652:urine; D016638:Critical Illness; D004334:Drug Administration Schedule; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D000077287:Levetiracetam; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives; D011725:Pyridines / Q000008:administration & dosage; D065667:Renal Elimination / Q000502:physiology*; D012307:Risk Factors; D013844:Thiazoles / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D011725:Pyridines; D013844:Thiazoles; D000077287:Levetiracetam; D003404:Creatinine; C552171:edoxaban; D010889:Piracetam
keywords: antibiotics; augmented renal clearance; creatinine clearance; critically ill; hyperfiltration; pharmacodynamic dosing; pharmacokinetics