Optimized meropenem dosage regimens using a pharmacokinetic/pharmacodynamic population approach in patients undergoing continuous venovenous haemodiafiltration with high-adsorbent membrane.

BACKGROUND: The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane. OBJECTIVES: To develop a PK/pharmacodynamic (PD) model for meropenem in critically ill sepsis patients undergoing continuous venovenous haemodiafiltration (CVVHDF) with the oXiris® membrane, and to design an optimal dosing regimen assessed according to the PTA. METHODS: A prospective, open-label, observational PK trial was performed (EUDRACT 2011-005902-30). We conducted PK studies (plasma and ultrafiltrate) for at least 24 h after concomitant administration of CVVHDF and meropenem 1 g q8h. We constructed a PK model using the non-linear mixed-effects approach (NONMEM 7.3). We evaluated the suitability of different dosage regimens using Monte Carlo simulations and calculated the PTA as the percentage of subjects achieving a given percentage of time above the MIC (fT>MIC). RESULTS: The PK of meropenem was best captured by a two-open-compartment model with zero-order input kinetics and first-order elimination. Extracorporeal CL was 7.78 L/h [relative standard error (RSE) 16.45 L/h] and central compartment V (Vc) was 24.9 L (RSE 13.73 L). Simulations showed that, for susceptible Pseudomonas aeruginosa isolates (EUCAST MIC ≤2 mg/L) and attainment of 100%fT>MIC, 500 mg q8h given as extended (EI) or continuous infusion (CI) would be sufficient. For a target of 100%fT>4×MIC, CI of 3000 mg q24h or 2000 mg q8h administered as EI or CI would be required. CONCLUSIONS: We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.

Current practice in continuous renal replacement therapy: An epidemiological multicenter study. / Manejo actual de las terapias continuas de reemplazo renal: Estudio epidemiológico multicéntrico.

OBJECTIVE: The aim of the study is to ascertain the most relevant aspects of the current management of renal replacement therapy (RRT) in critically ill patients, and to analyze renal function recovery and mortality in patients undergoing RRT. METHODS: A non-interventional three-month observational study was made in 2012, with a follow-up period of 90 days, in 21 centers in Catalonia (Spain). Demographic information, severity scores and clinical data were obtained, as well as RRT parameters. INCLUSION CRITERIA: patients aged ≥ 16 years admitted to Intensive Care Units (ICUs) and subjected to RRT. RESULTS: A total of 261 critically ill patients were recruited, of which 35% had renal dysfunction prior to admission. The main reason for starting RRT was oliguria; the most widely used RRT modality was hemodiafiltration; and the median prescribed dose at baseline was 35mL/kg/h. The median time of RRT onset from ICU admission was one day. The mortality rate at 30 and 90 days was 46% and 54%, respectively, and was associated to greater severity scores and a later onset of RRT. At discharge, 85% of the survivors had recovered renal function. CONCLUSIONS: Current practice in RRT in Catalonia abides with the current clinical practice guidelines. Mortality related to RRT is associated to later onset of such therapy. The renal function recovery rate at hospital discharge was 85% among the patients subjected to RRT.

Manejo actual de las terapias continuas de reemplazo renal: Estudio epidemiológico multicéntrico / Current practice in continuous renal replacement therapy: An epidemiological multicenter study

OBJETIVO: Determinar las características más relevantes del manejo actual de las terapias continuas de reemplazo renal (TRRC), así como analizar la evolución de la función renal y la mortalidad de los pacientes tratados con estas terapias. MÉTODOS: Estudio observacional sin intervención de 3meses de duración en 2012 con un periodo de seguimiento de 90 días, realizado en 21 hospitales de Cataluña, en que se registraron escalas de gravedad, datos demográficos, clínicos y de las TRRC. CRITERIOS DE INCLUSIÓN: pacientes de ≥16 años ingresados en cuidados intensivos (UCI) tratados con TRRC. RESULTADOS: Se seleccionó a 261 pacientes. Un 35% tenía disfunción renal previa al ingreso. El principal motivo para iniciar las TRRC fue la oliguria, la modalidad más empleada fue la hemodiafiltración y la mediana de dosis prescrita al inicio fue de 35mL/kg/h. La mediana de tiempo de inicio de la TRRC desde el ingreso en UCI fue de un día. La mortalidad a los 30 y 90 días fue de 46 y 54%, respectivamente, y se relacionó con peores valores en las escalas de gravedad y con un inicio más tardío de la TRRC. Al alta hospitalaria, un 85% de los supervivientes había recuperado la función renal. CONCLUSIONES: El manejo de las TRRC en Cataluña se adecua a los estándares recomendados por las guías actuales. La mortalidad asociada a las TRRC se relaciona con un inicio más tardío. Un 85% de los pacientes tratados con TRRC recuperan la función renal al alta hospitalaria

OBJECTIVE: The aim of the study is to ascertain the most relevant aspects of the current management of renal replacement therapy (RRT) in critically ill patients, and to analyze renal function recovery and mortality in patients undergoing RRT. METHODS: A non-interventional three-month observational study was made in 2012, with a follow-up period of 90 days, in 21 centers in Catalonia (Spain). Demographic information, severity scores and clinical data were obtained, as well as RRT parameters. Inclusion criteria: patients aged ≥ 16 years admitted to Intensive Care Units (ICUs) and subjected to RRT. Results A total of 261 critically ill patients were recruited, of which 35% had renal dysfunction prior to admission. The main reason for starting RRT was oliguria; the most widely used RRT modality was hemodiafiltration; and the median prescribed dose at baseline was 35mL/kg/h. The median time of RRT onset from ICU admission was one day. The mortality rate at 30 and 90 days was 46% and 54%, respectively, and was associated to greater severity scores and a later onset of RRT. At discharge, 85% of the survivors had recovered renal function. CONCLUSIONS: Current practice in RRT in Catalonia abides with the current clinical practice guidelines. Mortality related to RRT is associated to later onset of such therapy. The renal function recovery rate at hospital discharge was 85% among the patients subjected to RRT