Vancomycin pharmacokinetics in critically ill patients receiving continuous venovenous haemodiafiltration (original) (raw)
Related papers
American Journal of Kidney Diseases, 1998
The clearance of vancomycin is significantly reduced in patients with acute, as well as, chronic renal failure. Although multiple-dosage regimen adjustment techniques have been proposed for these patients, there is little quantitative data to guide the individualization of vancomycin therapy in acute renal failure patients who are receiving continuous renal replacement therapy (CRRT). To determine appropriate vancomycin dosing strategies for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies in five stable hemodialysis patients with three hemofilters: an acrylonitrile copolymer 0.6 m 2 (AN69), polymethylmethacrylate 2.1 m 2 (PMMA), and polysulfone 0.65 m 2 (PS). Patients received 500 mg of vancomycin intravenously at least 12 hours before the start of the clearance study. The concentration of vancomycin in multiple plasma and dialysate/ultrafiltrate samples was determined by EMIT (Syva, Palo Alto, CA). The diffusional clearance and sieving coefficient (SC) of vancomycin were compared by a mixed-model repeated-measures analysis of variance (ANOVA) with filter and blood (Q B ), dialysate inflow (Q DI ), or ultrafiltration rate (Q UF ) as the main effects and patient as a random effect. Vancomycin was moderately protein bound in these patients; free fraction ranged from 49% to 83%. The SCs of the three filters were similar and significantly correlated with the free fraction of vancomycin (P ؍ 0.01; r 2 ؍ 0.465). Significant linear relationships were observed between the diffusional clearance of vancomycin and Q DI for all three filters: AN69 (slope ؍ 0.482; r 2 ؍ 0.880); PMMA (slope ؍ 0.853; r 2 ؍ 0.966); and PS (slope ؍ 0.658; r 2 ؍ 0.887). The slope of this relationship for the PMMA filter was significantly greater than that of the AN69 and PS filters. The clearance of vancomycin, urea, and creatinine, however, was essentially constant at all Q B s for all three filters. Thus, the clearance of vancomycin was not membrane dependent during CVVH. However, during CVVHD, membrane dependence of vancomycin clearance was noted at a Q DI greater than 16.7 mL/min; vancomycin clearance with PMMA at a Q DI of 25 mL/min was 66% and 43% greater than that with the AN69 and PS filters, respectively. CVVH (62% to 262%) and CVVHD (90% to 540%) can significantly augment the clearance of vancomycin in acute renal failure patients. Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH and CVVHD are proposed.
Vancomycin pharmacokinetics in acute renal failure: Preservation of nonrenal clearance
Clinical Pharmacology and Therapeutics, 1991
Introduction: The normal nonrenal clearance of vancomycin is reduced in patients with chronic renal failure (40 versus 6 mumin). The nonrenal clearance of vancomycin in patients with acute renal failure has not been characterized extensively. Purpose: To prospectively determine the pharmacokinetic profile of vancomycin in anuric patients with acute renal failure who are receiving continuous venovenous hemofiltration. Methoh: Vancomycin serum samples were obtained in 10 patients immediately before and 1 and 12 hours after a 1-hour infusion. Thirteen sets of data were obtained. Vancomycin concentration data were incorporated into a first-order, single-compartment model. Determinations for the area under the serum concentration-time curve were made by the trapezoidal rule.
Antimicrobial Agents and Chemotherapy, 2012
The vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (<30 ml/kg/h; n ؍ 10) or high (>30 ml/kg/h; n ؍ 77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough achievement occurred in only 32 (37%) patients. The primary endpoint of trough attainment significantly differed between HFR subgroups: 90% versus 30% in low-and high-HFR individuals, respectively (P < 0.001). Patients with subtherapeutic trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in those who achieved the trough goal. Irrespective of goal trough, an inverse correlation existed between HFR and serum vancomycin concentration (r ؍ ؊0.423; P < 0.001). In the subgroup of 14 methicillin-resistant Staphylococcus aureus (MRSA) patients, trough achievement was similar to the aggregate cohort (36%). Mortality at 28 days was unrelated to trough achievement in both the overall sample (P ؍ 0.516) and in culturepositive MRSA patients (P ؍ 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.
Critical care (London, England), 2014
IntroductionAchievement 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).MethodsThis 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 C...
BMC Anesthesiology, 2015
Background: Administration of vancomycin in critically ill patients needs close regulation. While subtherapeutical vancomycin serum concentration (VSC) is associated with increased mortality, accumulation is responsible for nephrotoxicity. Our study aimed to estimate the efficacy of a vancomycin-dosing protocol in reaching appropriate serum concentration in patients with and without kidney dysfunction. Methods: This was a retrospective study in critically ill patients treated with continuous infusion of vancomycin. Patients with creatinine clearance >50 ml/min (Group A) were compared to those with creatinine clearance ≤50 ml/min (Group B).
Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects
Clinical Pharmacology and Therapeutics, 1988
The renal handling of vancomycin is unknown. Previously reported studies have not achieved steady-state conditions with constant vancomycin concentrations. We measured systemic vancomycin clearance simultaneously with the renal clearances of vancomycin, creatinine, inufin, and para-aminohippurate in nine healthy subjects at steady-state serum vancomycin concentrations of 7 and 14 mg/L. For all steadystate observations the renal clearance of vancomycin was 89 ± 11 ml/min (mean ± SE), the clearance of inufin 105 ± 9 ml/min, the clearance of creatinine 117 ± 9 ml/min, and the clearance of paraaminohippuric acid 496 ± 41 ml/min. The systemic clearance of vancomycin was 131 ± 7 ml/min. The clearances of creatinine, inulin, and para-aminohippuric acid and the renal clearance of vancomycin were not statistically different at both steady-state vancomycin concentrations. The ratio of the renal clearance of vancomycin to the clearance of inulin was 0.89 ± 0.06 and to creatinine clearance 0.79 ± 0.05. Both ratios were independent of vancomycin concentration, urine flow rate, and filtration fraction. The systemic clearance of vancomycin was 10% greater at serum vancomycin concentrations of 14 mg/L than at 7 mg/L (p < 0.05) because of an increase in the nonrenal clearance. Therefore in healthy subjects, 30%
Pharmacokinetics of vancomycin in patients with various degrees of renal function
Antimicrobial Agents and Chemotherapy, 1984
The pharmacokinetics of vancomycin were characterized in 56 patients with different degrees of renal function after an intravenous dose of 18.4 + 4.7 mg kg-' (mean ± standard deviation). Seven subjects had a creatinine clearance (CLCR) of >60 ml min-' (group I), 13 had a CLCR of 10 to 60 ml min-1 (group II), and 36 had a CLCR of <10 ml min-l (group III). Serial serum samples (range, 3 to 8) were collected during the 168 h after drug administration. The serum concentration-time profile in all patients demonstrated monoexponential decay. The mean half-lives were 9.1, 32.3, and 146.7 h in groups I, II, and III, respectively. A significant decline in serum clearance (CLs) was also noted (62.7 to 28.3 to 4.87 ml min-' in groups I, II, and III, respectively). The steady-state volume of distribution varied from 0.72 to 0.90 liter kg-'. There was no significant relationship between the steady-state volume of distribution and CLCR. The observed relationship between CLs and CLCR (CLs = 3.66 + 0.689 CLCR; r = 0.8807) can be utilized to devise dosage schedules for patients with any degree of renal impairment. This relationship was utilized to develop a nomogram for initial and maintenance dosing of vancomycin.
International Journal of Antimicrobial Agents, 2014
This study aimed to describe the population pharmacokinetics of vancomycin in critically ill patients with refractory septic shock undergoing continuous venovenous high-volume haemofiltration (HVHF) and to define appropriate dosing for these patients. This was a prospective pharmacokinetic study in the ICU of a university hospital. Eight blood samples were taken over one vancomycin dosing interval. Samples were analysed by a validated liquid chromatography-tandem mass spectrometry assay. Non-linear mixed-effects modelling was used to describe the population pharmacokinetics. Dosing simulations were used to define therapeutic vancomycin doses for different HVHF settings. Nine patients were included (five male). The mean weight and SOFA score were 70 kg and 11, respectively. Mean HVHF settings were: blood flow rate, 240 mL/min; and haemofiltration exchange rate, 100 mL/kg/h. A linear two-compartment model with zero-order input adequately described the data. Mean parameter estimates were: clearance, 2.9 L/h; volume of distribution of central compartment (V 1 ), 11.8 L; volume of distribution of peripheral compartment (V 2 ), 18.0 L; and intercompartmental clearance, 9.3 L/h. HVHF intensity was strongly associated with vancomycin clearance (P < 0.05) and was a covariate in the final model. Simulations indicate that after a loading dose, vancomycin doses required for different HVHF intensities would be 750 mg every 12 h (q12 h) for 69 mL/kg/h, 1000 mg q12 h for 100 mL/kg/h and 1500 mg q12 h for 123 mL/kg/h. Continuous infusion would also be a valuable administration strategy. In conclusion, variable and much higher than standard vancomycin doses are required to achieve therapeutic concentrations during different HVHF settings.