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.

[Optimising the quality of the unit dose dispensing process through the implementation of the semi-automated Kardex system]. / Optimización de la calidad del proceso de dispensación de medicamentos en dosis unitaria mediante la implantación del sistema semiautomático Kardex.

OBJECTIVE: To evaluate the effect of the incorporation of the semi-automated Kardex medication storage and dispensing system on the quality of the filling process of medicine trolleys in unit doses. METHOD: The speed of filling medicine trolleys in unit doses using the Kardex system was analysed retrospectively (n = 33,946 dispensings) and compared with the manual filling system (n = 5,284 dispensings); different filling procedures were used and compared. For each filling system and procedure, we obtained information for the number of dispensings and the time spent carrying this out. The speed of the process was calculated as the number of dispensings per hour. In addition, the drugs contained in the Kardex system were checked and the correspondence between both the actual and the theoretical content was assessed. RESULTS: The speed of the trolley filling process, expressed as the number of dispensings per hour, increased from 394 with the manual system (filling trolleys individually, n = 5,284 dispensings) to 417, 540 and 592 with the Kardex system when trolleys were filled individually (n = 16,530 dispensings), or grouped in two (n = 10,369 dispensings) or in three (n = 7,047 dispensings) respectively, at the start of the filling process. The check of the contents in the Kardex system detected 36% of trays with differences in quantity, one tray with out of date medication and three trays which should in theory have been empty and contained medication. CONCLUSIONS: The Kardex system optimises the speed of trolley filling with regard to the manual system, provided that the trolleys are grouped at the time of starting the preparation. The check of the cabinet contents shows that possibilities of error exist, related to its handling, which can be minimised by incorporating bar codes into the system s replenishment process.

Optimización de la calidad del proceso de dispensación de medicamentos en dosis unitaria mediante la implantación del sistema semiautomático Kardex® / No disponible

Objetivo: Evaluar el impacto de la incorporación del sistema semiautomático del almacenaje y dispensación de medicamentos Kardex® sobre la calidad del proceso de llenado de carros de medicamentos en dosis unitaria. Método: Se analiza retrospectivamente la velocidad de llenado de carros de medicamentos en dosis unitaria utilizando el sistema Kardex® (n = 33.946 dispensaciones) comparativamente conel sistema de llenado manual (n = 5.284 dispensaciones); se utilizan y comparan diferentes procedimientos de llenado. Para cada sistema y procedimiento de llenado se obtiene el número de dispensaciones y el tiempo invertido en realizarlas y se calcula la velocidad de proceso expresada en número de dispensaciones por hora. También, se revisan los medicamentos contenidos en el Kardex® y se evalúa la concordancia entre el contenido real y teórico del mismo.Resultados: La velocidad del proceso de llenado de carros,expresada en número dispensaciones por hora, pasa de 394 con el sistema manual (llenado de carros individual, n = 5.284 dispensaciones)a 417, 540 y 592 con Kardex®, realizando el llenado individual (n = 16.530 dispensaciones), o agrupando los carros de2 en 2 (n = 10.369 dispensaciones) o de 3 en 3 (n = 7.047 dispensaciones), respectivamente, en el momento de iniciar el llenado.La revisión del contenido del Kardex® permite detectar un 36% de cubetas con diferencias en cantidad, una cubeta con (..) (AU)

Objective: To evaluate the effect of the incorporation of the semi-automated Kardex® medication storage and dispensing systemon the quality of the filling process of medicine trolleys in unitdoses.Method: The speed of filling medicine trolleys in unit dosesusing the Kardex® system was analysed retrospectively (n =33,946 dispensings) and compared with the manual filling system(n = 5,284 dispensings); different filling procedures were used and compared. For each filling system and procedure, we obtained information for the number of dispensings and the time spent carryingthis out. The speed of the process was calculated as the number of dispensings per hour. In addition, the drugs contained in the Kardex® system were checked and the correspondence between both the actual and the theoretical content was assessed. Results: The speed of the trolley filling process, expressed as the number of dispensings per hour, increased from 394 with the manual system (filling trolleys individually, n = 5,284 dispensings)to 417, 540 and 592 with the Kardex® system when trolleys were filled individually (n = 16,530 dispensings), or grouped in twos (n= 10,369 dispensings) or in threes (n = 7,047 dispensings)respectively, at the start of the filling process. The check of the contents in the Kardex® system detected 36% of trays with differences in quantity, one tray with out of date medication and threetrays which should in theory have been empty and contained (..) (AU)

[Perioperative management of chronic medications not related with surgical procedures]. / Manejo perioperatorio de la medicación crónica no relacionada con la cirugía.

The correct management of chronic medications not related with surgical procedures in the perioperative period has a relevant place because each year millions of patients around the world undergo surgical procedures. For this reason the assistencial team should be aware of the importance of continuate or discontinuate determinate drugs during perioperative period because some of them are considered an important risk factor in the development of complications. The key is to differentiate necessary from unnecessary medication. This is a complex aspect, little studied, which difficult clinical decisions and favours the coexistence of several trends of clinical practice. The purpose of this review is to describe the factors that determinate the continuity or suspension of chronic medications which are not related with surgery in the perioperative period and to provide practice recommendations in lights of available publications.

Manejo perioperatorio de la medicación crónica no relacionada con la cirugía / Perioperative management of chronic medications not related with surgical procedures

El correcto manejo de la medicación crónica no relacionada con la cirugía adquiere un papel relevante ya que en todo el mundo millones de pacientes se someten año tras año a intervenciones quirúrgicas. El equipo asistencial debe tener presente la importancia de continuar o suprimir determinados fármacos durante el perioperatorio ya que algunos de ellos se consideran un factor de riesgo en el desarrollo de complicaciones. La cuestión fundamental es diferenciar la medicación necesaria de la innecesaria, o bien perjudicial. Éste es un aspecto complejo y todavía poco estudiado lo cual dificulta en algunos casos la toma de decisiones y conlleva a la coexistencia de diversas tendencias de práctica clínica. En este trabajo se revisan los aspectos que condicionan la suspensión o continuidad de la medicación crónica que no está relacionada con la cirugía y se proporcionan recomendaciones prácticas para el manejo de la misma en base a la bibliografía disponible (AU)

[Caloric overload in critically ill patients treated with parenteral nutrition]. / Sobrecarga calórica en el paciente crítico tratado con nutrición parenteral.

OBJECTIVE: To assess the degree of hypernutrition of critically-ill patients under treatment with parenteral nutrition (PN) in a multi-purpose intensive care unit (ICU). SCOPE: Patients under treatment with parenteral nutrition in a multi-purpose intensive care unit. Prospective study lasting four months. INTERVENTION: The amounts of the daily dose of glucose, lipids and nitrogen were calculated in PN, enteral nutrition (EN), dextrose solution (DS) and propofol. The daily dose of glucose and lipid administered intravenously (i.v.) was assessed with respect to the recommended value (4-5 mg/kg/min and 1.5 g/kg/day, respectively) and with respect to the dose prescribed in the PN regime The total daily calorie intake (i.v. plus EN) was assessed with respect to the recommended value (25-35 kcal/kg/day). RESULTS: The study involved 30 patients totalling 488 days with PN. The total daily dose of i.v. lipids (PN plus propofol) exceeded the recommended value on 23.2% of the days with propofol (13 of 56) and on 3.7% of the days without propofol (16 of 432). The total daily dose of i.v. dextrose did not exceed any day the maximum metabolization threshold. On 28.2% of the days with EN and 39.6% of the days without EN, the total daily dose of i.v. dextrose exceeded the PN regimen. Similarly, on 41% of the days with propofol, the total daily dose of i.v. lipids exceeded the PN regimen. The total calorie intake (i.v. plus EN) exceeded the recommended value on 46.9% of the days with EN (51 of 109) and on 5% of the days without EN (19 of 379). CONCLUSION: The glucose of dextrose solution and the propofol lipid are not routinely discounted from the PN regime. A trend towards hypernutrition of the critically-ill patient is shown, especially on days with simultaneous treatment with PN and EN.

Sobrecarga calórica en el paciente crítico tratado con nutrición parenteral / Caloric overload in critically-ill patients treated with parenteral nutrition

Objetivo: Evaluar el grado de hipernutrición del paciente crítico en tratamiento con nutrición parenteral (NP) en una unidad de cuidados intensivos (UCI) polivalente. Ámbito: Pacientes en tratamiento con NP en una UCI polivalente. Estudio prospectivo de cuatro meses de duración. Intervención: Se cuantificó la dosis diaria de glucosa, lípido y nitrógeno procedente de la NP, la nutrición enteral (NE), el suero glucosado (SG) y el propofol. Se valoró la dosis diaria de glucosa y lípido administrado por vía intravenosa (IV) respecto al valor recomendado (4-5 mg/kg/min y 1,5 g/kg/día, respectivamente) y respecto a la dosis prescrita en la pauta de NP. Se evalúo el aporte calórico total diario (IV más NE) respecto al valor recomendado (25-35 kcal/kg/día).Resultados: Se estudiaron 30 pacientes que totalizaron 488 días con NP. La dosis diaria total de lípido IV (NP más propofol) superó el valor recomendado el 23,2 por ciento de los días con propofol (13 de 56) y el 3,7 por ciento de los días sin propofol (16 de 432). La dosis diaria total de glucosa IV no superó ningún día el umbral máximo de metabolización. El 28,2 por ciento de los días con NE y el 39,6 por ciento de los días sin NE la dosis diaria total de glucosa IV superó la pauta de NP. Igualmente el 41 por ciento de los días con propofol la dosis diaria total de lípido IV superó la pauta de NP. El aporte calórico total (IV más NE) sobrepasó el valor recomendado el 46,9 por ciento de los días con NE (51 de 109) y el 5 por ciento de los días sin NE (19 de 379).Conclusión: La glucosa procedente del SG y el lípido del propofol no se descuentan de forma rutinaria de la pauta de NP. Se demuestra una tendencia a sobrenutrir al paciente crítico, especialmente los días en tratamiento simultáneo con NP y NE (AU)

Objective: To assess the degree of hypernutrition of critically-ill patients under treatment with parenteral nutrition (PN) in a multi-purpose intensive care unit (ICU). Scope: Patients under treatment with parenteral nutrition in a multi-purpose intensive care unit. Prospective study lasting four months. Intervention. The amounts of the daily dose of glucose, lipids and nitrogen were calculated in PN, enteral nutrition (EN), dextrose solution (DS) and propofol. The daily dose of glucose and lipid administered intravenously (IV) was assessed with respect to the recommended value (4-5 mg/kg/min and 1.5 g/kg/day, respectively) and with respect to the dose prescribed in the PN regime The total daily calorie intake (IV plus EN) was assessed with respect to the recommended value (25-35 kcal/kg/day). Results: The study involved 30 patients totalling 488 days with PN. The total daily dose of IV lipids (PN plus propofol) exceeded the recommended value on 23.2% of the days with propofol (13 of 56) and on 3.7% of the days without propofol (16 of 432). The total daily dose of IV dextrose did not exceed any day the maximum metabolization threshold. On 28.2% of the days with EN and 39.6% of the days without EN, the total daily dose of IV dextrose exceeded the PN regimen. Similarly, on 41% of the days with propofol, the total daily dose of IV lipids exceeded the PN regimen. The total calorie intake (IV plus EN) exceeded the recommended value on 46.9% of the days with EN (51 of 109) and on 5% of the days without EN (19 of 379). Conclusion: The glucose of dextrose solution and the propofol lipid are not routinely discounted from the PN regime. A trend towards hypernutrition of the criticallyill patient is shown, especially on days with simultaneous treatment with PN and EN (AU)

[Quality of the home parenteral nutrition program: 14 years of experience at a general university hospital]. / Calidad del programa de nutrición parenteral a domicilio: 14 años de experiencia en un hospital general universitario.

The quality of home parenteral nutrition (NPD in its Spanish acronym) depends on the frequency and type of complication associated with NPD treatment and the likelihood of survival. The present study assesses the quality of the NPD programme in place in our hospital in terms of survival, infections and mechanical complications. A retrospective study was carried out into the clinical follow-up data of all the patients (n = 24) included in our NPD programme since its start in 1985 until 1998 (14 years). An estimate is made for: a) the annual index of infectious complications (IAC in its Spanish acronym), b) the annual index of mechanical complications (MAC in its Spanish acronym) and c) the likelihood of survival by means of the Kaplan-Meier method. The quality specifications adopted are those of the literature reflecting the current provision of NPD programmes and the survival values of patients undergoing dialysis for chronic kidney failure. The most frequent pathology in our context is benign (70.8%), distributed as follows: small bowel syndrome of ischaemic origin (45.8%), small bowel syndrome of non-ischaemic origin (12.5%) and idiopathic intestinal pseudo-obstruction (12.5%). The patients with benign pathologies present a higher survival rate than patients with neoplastic disease (95% in the fifth year of treatment versus 45% at twenty months), with a statistically significant difference. The annual index of infectious complications is 0.6 (median value of the 14 years studied). Similarly, the annual indices of obstructions and thromboses are 0.11 and 0.0095, respectively. In our opinion, the quality of the NPD programme in place at our hospital is highly satisfactory because both the survival rate and the annual indices of mechanical and infectious complications are acceptable with regard to the programmes in place in the international sphere. In addition, in terms of survival, NPD seems slightly more effective than dialysis for chronic kidney disease.

Calidad del programa de nutrición parenteral a domicilio 14 años de experiencia en un hospital general universitario / Quality of home parenteral nutrition programme: 14 years's experience at a general teaching hospital

La calidad del tratamiento con nutrición parenteral a domicilio (NPD) depende de la frecuencia y tipo de complicaciones asociadas al mismo, así como de la probabilidad de supervivencia. En este trabajo se evalúa la calidad del programa de NPD existente en nuestro hospital en términos de supervivencia, complicaciones infecciosas y complicaciones mecánicas. Se realiza un estudio retrospectivo de los datos del seguimiento clínico de todos los pacientes (n = 24) incluidos en el programa de NPD de nuestro centro desde su inicio en 1985 hasta 1998 (14 años). Se estiman: a) el índice anual de complicaciones infecciosas (IAC), b) el índice anual de complicaciones mecánicas (MAC) y c) la probabilidad de supervivencia mediante el método de Kaplan-Meier. Se toman como especificaciones de calidad los datos bibliográficos que reflejan la prestación actual de los programas de NPD existentes y los valores de supervivencia de los pacientes en diálisis por fracaso renal crónico. La patología más frecuente en nuestro medio es la benigna (70,8 por ciento) distribuyéndose como sigue: síndrome de intestino corto de origen isquémico (45,8 por ciento), síndrome de intestino corto de causa no isquémica (12,5 por ciento) y seudoobstrucción intestinal idiopática (12,5 por ciento). Los pacientes con patología benigna presentan una supervivencia más alta que los pacientes con enfermedad neoplásica (95 por ciento al quinto año de tratamiento frente a 45 por ciento a los 20 meses), siendo la diferencia estadísticamente significativa. El índice anual de complicaciones infecciosas es 0,6 (valor mediano de los 14 años estudiados). De igual modo los índices anuales de obstrucciones y trombosis son 0,11 y 0,0095, respectivamente. En nuestra opinión la calidad del programa de NPD existente en nuestro hospital es muy satisfactoria porque tanto la proporción de supervivencia como los índices anuales de complicaciones infecciosas y mecánicas son aceptables respecto a la prestación de los programas existentes a nivel internacional. Además, en términos de supervivencia la NPD resulta ligeramente más efectiva que la diálisis por fracaso renal crónico (AU)

The quality of home parenteral nutrition (NPD in its Spanish acronym) depends on the frequency and type of complication associated with NPD treatment and the likelihood of survival. The present study assesses the quality of the NPD programme in place in our hospital in terms of survival, infections and mechanical complications. A retrospective study was carried out into the clinical follow-up data of all the patients (n = 24) included in our NPD programme since its start in 1985 until 1998 (14 years). An estimate is made for: a) the annual index of infectious complications (IAC in its Spanish acronym), b) the annual index of mechanical complications (MAC in its Spanish acronym) and c) the likelihood of survival by means of the Kaplan-Meier method. The quality specifications adopted are those of the literature reflecting the current provision of NPD programmes and the survival values of patients undergoing dialysis for chronic kidney failure. The most frequent pathology in our context is benign (70.8%), distributed as follows: small bowel syndrome of ischaemic origin (45.8% ), small bowel syndrome of non-ischaemic origin (12.5%) and idiopathic intestinal pseudo-obstruction (12.5%). The patients with benign pathologies present a higher survival rate than patients with neoplasic disease (95% in the fifth year of treatment versus 45% at twenty months), with a statistically significant difference. The annual index of infectious complications is 0.6 (median value of the 14 years studied). Similarly, the annual indices of obstructions and thromboses are 0.11 and 0.0095, respectively. In our opinion, the quality of the NPD programme in place at our hospital is highly satisfactory because both the survival rate and the annual indices of mechanical and infectious complications are acceptable with regard to the programmes in place in the international sphere. In addition, in terms of survival, NPD seems slightly more effective than dialysis for chronic kidney disease (AU)

[Clinical application of the biological variability data of the thyroid hormones]. / Aplicación clínica de los datos de variabilidad biológica de las hormonas tiroideas.

BACKGROUND: The selection of laboratory tests with greater effectiveness for identifying patients with thyroid disorders (sensitivity) from non affected subjects (specificity) is, at present, under discussion. The study of biological variation can contribute to point out the laboratory tests with greater effectiveness. METHODS: Total blood was collected daily for five consecutive days from 25 healthy volunteers, which maintaining their usual life style all over the period. RESULTS: The biological coefficients of variation--within and between--subject, the individuality indexes and the critical differences between consecutive results are estimated. The effect of pulsatility over the results obtained is also discussed. CONCLUSIONS: The most effective laboratory test for the diagnosis of thyroid disorders is TSH, with the precaution of doing a second analysis if the first result falls close to either the lower or higher reference range limits. The best laboratory tests for the monitoring of hypo- and hyperthyroidism are total T4 and free T4, in which a critical difference between consecutive results higher than 15% indicates a significant change in the patient status.