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.

An inflammation-based prognostic score, the C-reactive protein/albumin ratio predicts the morbidity and mortality of patients on parenteral nutrition.

BACKGROUND: There is no "gold standard" score for predicting poor-nutrition-related outcomes. The objective of this study was to identify the optimal predictive score, based on inflammatory parameters, for the clinical outcomes of parenteral nutrition (PN). MATERIAL AND METHODS: This was a 4-year retrospective observational study of 460 patients treated with PN. C-reactive protein (CRP), prealbumin, albumin, CRP/prealbumin and CRP/albumin were studied as potential prognostic scores at the beginning of PN for clinical outcomes during PN. Three different statistical approaches were developed: 1) A univariate analysis of each of the 5 prognostic scores and 5 multivariate models for CRP/albumin and CRP/prealbumin to study their association with exitus, infection, sepsis, liver failure, renal impairment, cancer, intensive care unit stay, mechanical ventilation; 2) Univariate and multivariate survival analysis of PN length, intensive care unit (ICU) length of saty and days of mechanical ventilation vs CRP/albumin and CRP/prealbumin; 3) A ROC analysis of the prognostic accuracy of CRP/albumin and CRP/prealbumin over morbidity/mortality. RESULTS: 1) CRP, albumin and CRP/albumin gave more information about morbidity/mortality than prealbumin and CRP/prealbumin. CRP/albumin was statistically significant for exitus (OR 1.85; CI 95%: 1.00-3.45), infection (OR 2.15; CI 95%: 1.22-3.80), sepsis (OR 2.82; CI 95%: 1.69-4.70) and liver failure (OR 2.66; CI 95%: 1.55-4.58). CRP/prealbumin for sepsis was (OR 2.21; CI 95%: 1.34-3.64) and for liver failure (OR 2.04; CI 95%: 1.17-3.53); 2) CRP/albumin and CRP/prealbumin significantly predict PN duration, days in ICU and days on mechanical ventilation; 3) and are related to exitus, infection, sepsis and liver failure. CONCLUSION: The CRP/albumin score at the beginning of PN treatment has more prognostic capability than CRP/prealbumin, albumin or prealbumin. The systematic use of this score could help to identify those patients with higher risk.

[Intermediate syndrome after organophosphate poisoning despite continuous infusion of pralidoxime]. / Síndrome intermedio en el transcurso de una intoxicación por organofosforados a pesar de una infusión continua de pralidoxima.

Acute organophosphate poisoning leads to a cholinergic crisis secondary to an acetylcholine rise, developed by an acetylcholinesterase inhibition. In some cases, after the resolution of the initial cholinergic signs and symptoms, an intermediate syndrome occurs, characterized by a delayed development of proximal and diaphragmatic muscle paralysis. We describe a case of a 67-year-old man who developed an intermediate syndrome after oxydemeton-metryl ingestion in a suicide attempt, despite a continuous pralidoxime infusion. Several hypotheses have been developed to explain the aetiology of this intermediate syndrome (neuromuscular junction dysfunction, inadequate poisoning treatment, late beginning of the oxime administration, etc). Intermediate syndrome manifestation will depend on the organophosphate's organism persistence and its chemical structure, and also on the time elapsed between the poisoning and the antidote administration.

[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.

Parenteral fish oil and liver function tests in hospitalized adult patients receiving parenteral nutrition: A propensity score-matched analysis.

BACKGROUND & AIMS: Intravenous fat emulsions are associated with liver disease and there is some evidence that the administration of intravenous fish oil (FO) may be useful in reversing it. The aim of our study was to assess whether there are differences in the changes of liver function tests (LFTs) in hospitalized adult patients with parenteral nutrition (PN) with FO and vegetal lipids vs patients without FO. The secondary aim was to study the relationship between impaired LFT and FO. METHODS: This was a 4-year, propensity score-matched analysis including patients aged ≥18 years treated with PN for ≥10 days. The exclusion criteria were previous liver disease, biliary disorders or pancreatic cancer, and altered initial LFT values. Patients were classified into 2 groups: FO cohort (patients who received FO - in addition to vegetal oil - after the first week of PN) and the vegetal oil cohort (patients who received only vegetal oil). A propensity score matched cohort design was developed. Univariate analyses were used to study the changes in LFTs. To evaluate whether LFT alterations vary with FO administration, four stepwise multiple linear regression models were conducted. RESULTS: 52 patients were included, 52% men, median 66 (55-75) years and 69 kg (61.7-78.8), with 18.5 (14-31.8) days of PN treatment. Maximum FO supplementation was 23%. During the first week with PN (none of the groups receiving FO), gammaglutamyl transferase (GGT), alkaline phosphatase (AP) and total bilirubin (BIL) increased significantly. Comparing LFT values at seven days of PN with at the end of PN treatment, the univariate analysis showed a better response for the FO group. The group without FO showed a significant increase for GGT and AP. In multivariate models, the percentage of FO administered was associated with a decrease in GGT, B = -0.33 [CI 95% = -0.54/-0.12], in AP, B = -0.12 [CI 95% = -0.20/-0.03] and ALT, B = -0.12 [CI 95% = -0.21/-0.024]. CONCLUSIONS: Lipid composition plays a significant role in LFT alteration associated with PN, and FO intravenous lipid emulsions (ILEs) minimize disturbance of LFTs in hospitalized adult patients.

Use of Subjective Global Assessment, Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 to evaluate the nutritional status of non-critically ill patients on parenteral nutrition.

OBJECTIVE: To evaluate the nutritional status of non-critically ill digestive surgery patients at the moment of parenteral nutrition initiation using three different nutritional test tools and to study their correlation. To study the association between the tests and the clinical and laboratory parameters used in the follow-up of PN treatment. METHODS: Prospective study over 4 months. Anthropometric and clinical variables were recorded. Results of Subjective Global Assessment; Patient-Generated Subjective Global Assessment; and Nutritional Risk Screening 2002 were compared applying kappa test. Relationship between the clinical and laboratory parameters with Subjective Global Assessment was studied by multinominal regression and with the other two tests by multiple linear regression models. Age and sex were included as adjustment variables. RESULTS: Malnutrition in 45 studied patients varied from 51% to 57%. Subjective Global Assessment correlated well with Patient-Generated Subjective Global Assessment and Nutritional Risk Screening 2002 (κ = 0531 p = 0.000). The test with the greatest correlation with the clinical and analytical variables was the Nutritional Risk Screening 2002. Worse nutritional state in this test was associated with worse results in albumin (B = -0.087; CI = -0.169/-0.005], prealbumin (B = -0.005; CI = [-0.011/-0.001]), C-reactive protein (B = 0.006;CI = [0.001/ 0.011]) and leukocytes (B = 0.134; CI = [0.031/0.237]) at the en of parenteral nutrition treatment. CONCLUSIONS: Half of the digestive surgery patients were at malnutritional risk at the moment of initiating parenteral nutrition. Nutritional Risk Screening 2002 was the test with best association with the parameters used in the clinical follow-up of parenteral nutrition treated patients.

Objetivo: Evaluar el estado nutricional de pacientes no críticos de cirugía digestiva, en el momento de iniciar la nutrición parenteral, utilizando tres tests de evaluación nutricional. Estudiar la correlación entre los tests y su asociación con los parámetros clínicos y de laboratorio utilizados para el seguimiento de estos pacientes. Métodos: Estudio prospectivo de 4 meses. Se recogen variables antropométricas y clínicas. Los resultados de Subjective Global Assessment, Patient-Generated Subjective Global Assessment y Nutritional Risk Screening 2002 se comparan mediante test kappa. La relación entre las variables clínicas y de laboratorio con Subjective Global Assessment se estudian con regresión multinominal; y con Patient-Generated Subjective Global Assessment y Nutritional Risk Screening mediante regresión lineal múltiple. Edad y sexo se introdujeron como variables de ajuste. Resultados: La desnutrición en 45 pacientes estudiados variaba entre el 51% y el 57%. Subjective Global Assessment correlacionaba bien con Patient-Generated Subjective Global Assessment y el Nutritional Risk Screening (= 0,531 p = 0,000). Nutritional Risk Screening 2002 mostró mejor asociación con variables clínicas y analíticas: peor estado nutricional en este test se asoció con peor comportamiento de albúmina (B = -0,087; CI = -0,169/-0,005]); prealbumina (B = -0,005; CI = [-0,011/ 0,001]), proteína C reactiva (B = 0,006;CI = [0,001/0,011]) y leucocitos (B = 0,134; CI = [0,031/0,237]) al final de la nutrición parenteral. Discusión: La mitad de los pacientes de cirugía digestiva presentan algún grado de desnutrición en el momento de iniciar la nutrición parenteral. El Nutritional Risk Screening 2002 se mostró como el test con mayor relación con las variables utilizadas en el seguimiento clínico de los pacientes con nutrición parenteral.

Liver function test alterations associated with parenteral nutrition in hospitalized adult patients: incidence and risk factors.

BACKGROUND: Parenteral nutrition-associated liver dysfunction can be progressive and irreversible, particularly in children and patients with long-term treatment. This study has assessed the incidence of abnormal liver function tests in hospitalized adults during short term parenteral nutrition (PN) and has investigated risk factors for developing alterations of each parameter. METHODS: A prospective cohort study of parenteral nutrition treated patients with preserved liver function at baseline. Variables examined included nutritional and clinical data and laboratory parameters. Determinations were performed before starting PN and weekly until liver function test alteration was observed. Risk factors were investigated by four stepwise forward logistical regressions. RESULTS: Eighty patients were included, 57.5% had liver function test alterations. PN mean duration was 15.9 (8-54) days. Mean days with PN and additional enteral/ oral nutrition were 1.5 (0-20). The following associations were found: gamma-glutamyl-transferase increased with soybean lipid intake and absolute diet; alkaline phosphatase increased with septic shock; alanine transaminase increased with septic shock, hyperglycemia and elevated creatinine; total bilirubin increased with septic shock, absolute diet, low prealbumin and glucose, and high creatinine. CONCLUSIONS: The incidence of altered liver function tests is high in adult hospitalized patients treated with short-term PN. However, the effect of nutritional factors in this alteration is low. Oral/enteral nutrition and reduction of soybean lipid supply can reduce increases in some liver function tests such as gamma-glutamyl-transferase and total bilirubin. The high association between all liver function tests and clinical systemic-hypermetabolic variables suggest the importance of specific nutritional strategies for this condition.