Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics

<jats:p>Augmented renal clearance (<jats:styled-content style="fixed-case">ARC</jats:styled-content>) has been reported in approximately 30–65% of patients in the intensive care unit (<jats:styled-content style="fixed-case">ICU</jats:styled-content>) despite the presence of a normal serum creatinine concentration. In certain <jats:styled-content style="fixed-case">ICU</jats:styled-content> patient populations (e.g., patients with sepsis or trauma), the incidence increases to roughly 50–85%. Risk factors for <jats:styled-content style="fixed-case">ARC</jats:styled-content> 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 <jats:styled-content style="fixed-case">II</jats:styled-content> (APACHE II) or modified Sequential Organ Failure Assessment (SOFA) score at <jats:styled-content style="fixed-case">ICU</jats:styled-content> admission. In addition, patient populations with the highest reported incidence of <jats:styled-content style="fixed-case">ARC</jats:styled-content> include those with major trauma, sepsis, traumatic brain injury, subarachnoid hemorrhage, and central nervous system infection. Due to the high incidence of <jats:styled-content style="fixed-case">ARC</jats:styled-content> in patients with a normal serum creatinine concentration, clinicians should consider screening <jats:styled-content style="fixed-case">ICU</jats:styled-content> patients deemed high risk by using the <jats:styled-content style="fixed-case">ARC</jats:styled-content> 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 <jats:styled-content style="fixed-case">ARC</jats:styled-content> and subtherapeutic antibiotic concentrations as well as literature suggesting worse clinical outcomes; thus, the risk of underdosing antibiotics in a patient with <jats:styled-content style="fixed-case">ARC</jats:styled-content> could increase the risk of treatment failure. This review examines strategies to overcome <jats:styled-content style="fixed-case">ARC</jats:styled-content> and summarizes current pharmacokinetic and pharmacodynamic literature in patients with <jats:styled-content style="fixed-case">ARC</jats:styled-content> in an effort to provide dosing guidance for this patient population.</jats:p>