Over-increased creatinine renal clearance in septic patients and implications for vancomycin optimization

Abstract

Introduction: The hyperdynamic stage occurring in sepsis may be responsible for an increase in renal blood flow that may lead to increased elimination of some drugs, namely vancomycin. The aim of this study was to evaluate the effects of 24-hour creatinine clearance (CrCL) higher than 130 ml/min/1.73 m 2 on vancomycin serum levels, and to identify an accurate marker of this condition. Methods: This study was carried out in a multipurpose ICU, on 120 critical septic patients, 36% with septic shock (42 patients), 67 men (72.5%), average age 56 +/- 21 years, average APACHE II score and Simplified Acute Physiology Score (SAPS) II of 17.2 and 42.2, respectively. We studied 120 consecutive vancomycin treatments (continuous perfusion) and we assessed therapeutic levels (20 to 30 mug/ml) on days 1, 2 and 3 (V1, V2 and V3). Patients were divided into two groups according to CrCL: G1 2 (n = 77); G2 >130 ml/min/1.73 m 2 (n = 43). Both groups had similar vancomycin dosage on day 0 (47.7/46.6 mg/kg; P = 0.26). Results: Average age, APACHE II score and SAPS II were 62.6/44 years, 18.8/14.2 and 45/36.9, respectively, for G1 and G2 (P <0.05). Average CrCL in G1: 76.7 ml/min/1.73 m 2; average CrCL in G2: 176 ml/min/1.73 m 2 (P <0.05). Serum proteins and albumin were, respectively, 5.26/5.64 g/dl and 2.84/3.17 g/dl (P <0.05), and urinary creatinine (UCr), urinary urea and 24-hour urine output were 34.6/71 mg/dl, 437/625 mg/dl and 2,450/ 2,846 ml, respectively (P <0.05). V1, V2 and V3 were 20/14.3, 24.3/17.6 and 26.5/20.3 mug/ml, respectively, for G1 and G2 (P <0.05 on each day). The correlations between V1 and CrCL were -0.47 (G1) and -0.33 (G2), both with P <0.05. The area under the curve (AUC) of the receiving operating curves of UCr, urinary urea and blood urea nitrogen (BUN) as markers of high clearance status (>130) were 0.85 (95% CI = 0.77 to 0.91), 0.72 (95% CI = 0.63 to 0.80) and 0.66 (95% CI = 0.55 to 0.73), respectively, and this area was maximal for a subgroup of patients (76 patients) without shock (AUC: 0.9; 95% CI = 0.81 to 0.96 for UCr). Best cutoff point for UCr: > 58mg/dl; for BUN: <17 mg/dl. Conclusions: Over-increased CrCL identifies a subgroup of younger patients, with lower severity scores and high incidence of subtherapeutic vancomycin concentrations on the first 3 days - especially on day 1 (39/43 patients; 90.7%). A UCr concentration above 58 mg/dl can be a sensitive (70%) and specific (87%) marker of this condition. The addition of BUN <17 mg/dl as a second marker increases specificity to 97.4%.