title: Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients.
abstract: BACKGROUND
  Improved methods to optimize drug dosing in the critically ill are urgently needed. Traditional prescribing culture involves recognition of factors that mandate dose reduction (such as renal impairment), although optimizing drug exposure, through more frequent or augmented dosing, represents an evolving strategy. Elevated creatinine clearance (CLCR) has been associated with sub-therapeutic antibacterial concentrations in the critically ill, a concept termed augmented renal clearance (ARC). We aimed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients, while also examining demographic, physiological and illness severity characteristics that may help identify this phenomenon.
  
  
  METHODS
  This prospective observational study was performed in a 30-bed tertiary level, university affiliated, adult intensive care unit. Consecutive traumatized and septic critically ill patients, receiving antibacterial therapy, with a plasma creatinine concentration ≤110 μmol/L, were eligible for enrolment. Pulse contour analysis (Vigileo / Flo Trac system, Edwards Lifesciences, Irvine, CA, USA), was used to provide continuous cardiac index (CI) assessment over a single six-hour dosing interval. Urinary CLCR measures were obtained concurrently.
  
  
  RESULTS
  Seventy-one patients contributed data (sepsis n = 43, multi-trauma n = 28). Overall, 57.7% of the cohort manifested ARC, although there was a greater prevalence in trauma (85.7% versus 39.5%, P <0.001). In all patients, a weak correlation was noted between CI and CLCR (r = 0.346, P = 0.003). This was mostly driven by septic patients (r = 0.508, P = 0.001), as no correlation (r = -0.012, P = 0.951) was identified in trauma. Those manifesting ARC were younger (P <0.001), male (P = 0.012), with lower acute physiology and chronic health evaluation (APACHE) II (P= 0.008) and modified sequential organ failure assessment (SOFA) scores (P = 0.013), and higher cardiac indices (P = 0.013). In multivariate analysis, age ≤50 years, trauma, and a modified SOFA score ≤4, were identified as significant risk factors. These had greater utility in predicting ARC, compared with CI assessment alone.
  
  
  CONCLUSIONS
  Diagnosis, illness severity and age, are likely to significantly influence renal drug elimination in the critically ill, and must be regularly considered in future study design and daily prescribing practice.
authors: Andrew A
authors: AA
authors: Udy
authors: Jason A
authors: JA
authors: Roberts
authors: Andrew F
authors: AF
authors: Shorr
authors: Robert J
authors: RJ
authors: Boots
authors: Jeffrey
authors: J
authors: Lipman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood*; D005260:Female; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology*; D008875:Middle Aged; D009104:Multiple Trauma / Q000097:blood* / Q000175:diagnosis*; D010865:Pilot Projects; D011446:Prospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003404:Creatinine