title: The importance of empiric antibiotic dosing in critically ill trauma patients: Are we under-dosing based on augmented renal clearance and inaccurate renal clearance estimates?
abstract: An accurate assessment of creatinine clearance (CrCl) is essential when dosing medications in critically ill trauma patients. Trauma patients are known to experience augmented renal clearance (i.e., CrCl ≥130 mL/min), and the use of CrCl estimations may be inaccurate leading to under-/over-dosing of medications. As such, our Level I trauma center began using measured CrCl from timed urine collections to better assess CrCl. This study sought to determine the prevalence of augmented renal clearance and the accuracy of calculated CrCl in critically ill trauma patients.
  
  
  
  This observational study evaluated consecutive ICU trauma patients with a timed 12-hour urine collection for CrCl. Data abstracted were patient demographics, trauma-related factors, and CrCl. Augmented renal clearance was defined as measured CrCl ≥130 mL/min. Bias and accuracy were determined by comparing measured and estimated CrCl using the Cockcroft-Gault and other formulas. Bias was defined as measured minus calculated CrCl, and accuracy was calculated CrCl that was within 30% of measured.
  
  
  
  There were 65 patients with a mean age of 48 years, serum creatinine (SCr) of 0.8 ± 0.3 mg/dL, and injury severity score of 22 ± 14. The incidence of augmented renal clearance was 69% and was more common when age was <67 years and SCr <0.8 mg/dL. Calculated CrCl was significantly lower than measured (131 ± 45 mL/min vs. 169 ± 70 mL/min, p < 0.001) and only moderately correlated (r = 0.610, p < 0.001). Bias was 38 ± 56 mL/min, which was independent of age quartile (p = 0.731). Calculated CrCl was inaccurate in 33% of patients and trauma-related factors were not predictive.
  
  
  
  The prevalence of augmented renal clearance in critically ill trauma patients is high. Formulas used to estimate CrCl in this population are inaccurate and could lead to under-dosing of medications. Measured CrCl should be used in this setting to identify augmented renal clearance and allow for more accurate estimates of renal function.
  
  
  
  Prognostic/epidemiologic study, level III.
authors.affiliation: From Midwestern University, College of Pharmacy-Glendale (J.F.B.); and Honor Health-John C. Lincoln Medical Center (A.J.M., M.B., A.K.H., J.F.S., F.R.A-O., G.R.S., J.K.D.), Phoenix, Arizona.
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Barletta
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Mangram
authors.forename: Marilyn
authors.initials: M
authors.lastname: Byrne
authors.forename: Alexzandra K
authors.initials: AK
authors.lastname: Hollingworth
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Sucher
authors.forename: Francis R
authors.initials: FR
authors.lastname: Ali-Osman
authors.forename: Gina R
authors.initials: GR
authors.lastname: Shirah
authors.forename: James K
authors.initials: JK
authors.lastname: Dzandu
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003404:Creatinine / Q000378:metabolism; D016638:Critical Illness; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D007668:Kidney / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014947:Wounds and Injuries / Q000150:complications / Q000628:therapy*
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine