Browsing by Author "Roberts, JA"
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- A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearancePublication . Baptista, JP; Udy, AA; Sousa, E; Pimentel, J; Wang, L; Roberts, JA; Lipman, JINTRODUCTION: Increasingly, derived estimates of glomerular filtration, such as the modification of diet in renal disease (MDRD) equation and Cockcroft-Gault (CG) formula are being employed in the intensive care unit (ICU). To date, these estimates have not been rigorously validated in those with augmented clearances, resulting in potentially inaccurate drug prescription. METHODS: Post-hoc analysis of prospectively collected data in two tertiary level ICU's in Australia and Portugal. Patients with normal serum creatinine concentrations manifesting augmented renal clearance (ARC) (measured creatinine clearance (CLCR) > 130 ml/min/1.73 m2) were identified by chart review. Comparison between measured values and MDRD and CG estimates were then undertaken. Spearman correlation coefficients (rs) were calculated to determine goodness of fit, and precision and bias were assessed using Bland-Altman plots. RESULTS: Eighty-six patients were included in analysis. The median [IQR] measured CLCR was 162 [145-190] ml/min/1.73 m2, as compared to 135 [116-171], 93 [83-110], 124[102-154], and 108 [87-135] ml/min/1.73 m2 estimated by CG, modified CG, 4-variable MDRD and 6-variable MDRD formulae. All of the equations significantly under-estimated the measured value, with CG displaying the smallest bias (39 ml/min/1.73 m2). Although a moderate correlation was noted between CLCR and CG (rs = 0.26, P = 0.017) and 4-variable MDRD (rs = 0.22, P = 0.047), neither had acceptable precision for clinical application in this setting. CG estimates had the highest sensitivity for correctly identifying patients with ARC (62%). CONCLUSIONS: Derived estimates of GFR are inaccurate in the setting of ARC, and should be interpreted with caution by the physician. A measured CLCR should be performed to accurately guide drug dosing.
- Decreasing the time to achieve therapeutic vancomycin concentrations in critically ill patients: developing and testing of a dosing nomogramPublication . Baptista, JP; Roberts, JA; Sousa, E; Freitas, R; Deveza, N; Pimentel, JINTRODUCTION: Achievement of optimal vancomycin exposure is crucial to improve the management of patients with life-threatening infections caused by susceptible Gram-positive bacteria and is of particular concern in patients with augmented renal clearance (ARC). The aim of this study was to develop a dosing nomogram for the administration of vancomycin by continuous infusion for the first 24 hours of therapy based on the measured urinary creatinine clearance (8 h CLCR). METHODS: This single-center study included all critically ill patients treated with vancomycin over a 13-month period (group 1), in which we retrospectively assessed the correlation between vancomycin clearance and 8 h CLCR. This data was used to develop a formula for optimised drug dosing. The efficiency of this formula was prospectively evaluated in a second cohort of 25 consecutive critically ill patients (group 2). Vancomycin serum concentrations between 20 to 30 mg/L were considered adequate. ARC was defined as 8 h CLCR more than 130 ml/min/1.73 m(2). RESULTS: The incidence of ARC was 36% (n = 29/79) and 40% (10/25) in group 1 (n = 79) and 2 (n = 25), respectively. The mean serum vancomycin concentration on day 1 was 21.5 (6.4) and 24.5 (5.2) mg/L, for both groups respectively. On the treatment day, vancomycin plasma clearance was 5.12 (1.9) L/h in group 1 and correlated significantly with the 8 h CLCR (r(2) = 0.66; P < 0.001). The achievement of adequate vancomycin serum concentrations in group 2 was 84% (n = 21/25) versus 51% (n = 40/79) - P < 0.005. CONCLUSIONS: This new vancomycin nomogram enabled the achievement of adequate serum concentrations in 84% of the patients on the first day of treatment.