New Predictive Equations for Serum Ionized Calcium in Hospitalized Patients.

OBJECTIVE: To study a new and easy way to calculate equations to predict ionized calcium (Ca2+) for adult hospitalized patients with the usual laboratory and clinical parameters. SUBJECTS AND METHODS: This retrospective observational study was conducted in a third-level university hospital. An initial learning cohort (cohort L: 269 patients) was selected to derive the new equations. These equations were tested in a validation of another cohort (cohort V: 146 patients). Patients selected were hospitalized adults who had simultaneous determinations of Ca2+ and serum total calcium (CaTot). They were classified using their estimated glomerular filtration rate (GFRe) into normal function, moderate and severe kidney dysfunction. Demographic and biochemical parameters, in addition to comorbidities, were collected from hospital databases. Nine published equations to predict Ca2+ and 2 widely used equations to predict corrected CaTot were also selected to be compared to newer equations for accuracy in detecting serum calcium alterations. New equations were derived by a multiple linear-regression analysis from patients in cohort L. RESULTS: Three equations were derived containing the CaTot square root as the main independent variable. Equation 1: Ca2+ = 0.815 × CaTot(0.5). Equation 2: Ca2+ = 0.826 × CaTot(0.5) - 0.023 × renal function. Equation 3: Ca2+ = 0.813 × CaTot(0.5) - 0.006 × albumin(0.75) + 0.079. These equations performed better than published equations to predict Ca2+ when their error measures were analyzed in cohort V, even in special populations such as critically ill and very old patients. CONCLUSIONS: Three new equations predicting Ca2+ were derived requiring easily available clinical and laboratory parameters. They could be valuable in predicting hypocalcemia but are of limited use in hypercalcemia.

Design of a score to identify hospitalized patients at risk of drug-related problems.

PURPOSE: The potential impact of drug-related problems (DRP) on morbidity and mortality is a serious concern in hospitalized patients. This study aimed to design a risk score to identify patients most at risk of a DRP. METHODS: Data from patients admitted to a tertiary university hospital between January and August 2009 were used to design the risk score (training set). DRP were detected through a pharmacy warning system integrated in the computerized medical history. The variables associated with developing a DRP were identified through a binary multivariate logistic regression analysis and were used to compute the DRP risk score, which was subsequently validated in patients admitted between September and December 2009 (validation set). RESULTS: Of the 8713 patients included in the training set, at least one DRP was detected in 2425 (27.8%). Prescription of a higher number of drugs, higher comorbidity, advanced age, certain groups of the Anatomical Therapeutic Chemical classification system, and some major diagnostic categories were associated with risk of DRP. These variables were used to compute the DRP risk score. The area under the receiver operator characteristic curve was 0.778 (95%CI [0.768, 0.789]). Of the 4058 admissions included in the validation set, at least one DRP was detected in 876 (21.6%). The area under the receiver operator characteristic curve was 0.776 (95%CI [0.759, 0.792]). CONCLUSIONS: Knowledge of the variables associated with DRP could aid their early detection in at-risk patients. The use of an application that can be continually updated in daily clinical practice helps to optimize resources.

Comparison of two isocaloric parenteral nutrition regimens with different protein content - A propensity-score matched comparative study.

OBJECTIVE: this study aimed to assess the effects of two isocaloric parenteral nutrition (PN) regimens with different protein content and non-protein calorie to nitrogen ratio (NPCNR) on the evolution of nutritional parameters and outcomes in adult inpatients. METHODS: this was a retrospective quasi-experimental study performed in a 400-bed tertiary hospital. Adult inpatients were initially eligible if they had received ≥ 4 days of PN with NPCNR ≥ 100 or ≤ 90 in a period of three years. Patients were propensity-score matched to adjust for differences, resulting in two final cohorts: Cohort "Medium-P" included patients receiving PN with NCPCNR ≥ 100 and cohort "High-P", receiving PN with NCPCNR ≤ 90. The main variables were differences in plasma albumin, prealbumin, cholesterol, and lymphocyte count, days requiring PN, length of stay, and mortality at 90 days. RESULTS: 202 patients were finally recruited and divided into the two equal cohorts. Patients were mainly male (122; 60.4 %), surgical (149; 73.8 %), critically ill (100; 49.5 %), with high nutritional risk (141; 69.8 %) and with a neoplasm (145; 71.8 %). PN provided 25 kcal/kg/day, but protein intake was 0.25 g/kg/day higher in the "High-P" cohort. Baseline characteristics and biochemistry were not different between the two cohorts. The "High-P" cohort presented a smaller difference at the end of PN for lymphocytes, more days with hyperglycaemia, and more days requiring PN. The rest of variables did not differ. CONCLUSIONS: high doses of protein (lower NPCNR) did not present advantages compared to medium doses of protein (higher NPCNR) when providing isocaloric PN in adult inpatients.

Factors associated with all-cause mortality at 90 days in hospitalized adult patients who received parenteral nutrition.

Introduction: Objective: this study aimed to assess the main factors related to mortality in a cohort of hospitalized adult patients who required parenteral nutrition (PN) considering their characteristics, type of admission, procedures, nutritional data, and adverse events. Methods: a retrospective study was performed in a 400-bed university hospital. All adult inpatients that had received ≥ 4 days as first course of PN within 24 months were included. Patients with long-term (> 90 days) or home PN were excluded. The main variable was all-cause mortality at 90 days after the end of PN. Initial independent variables were anthropometric and demographic data, admission characteristics, severity, comorbidity, surgical/medical procedures, baseline biochemical parameters, nutritional risk, and other nutritional data, medications, and adverse events during PN. A Cox proportional hazards regression model was planned to analyze time-to-event data. Results: a total of 634 patients entered the study and 140 (22.1 %) died. Patients were mainly: surgical 471 (74.3 %), male 393 (62.0 %), and age 69.0 (67.8-70.1) years old. The survival time for the entire cohort was 74.0 (95 % CI: 71.6-76.6) days. The final model included 14 variables, with severity and comorbidity being the main ones, but including also anastomotic suture dehiscence, sepsis during PN, days with hyperglycemic events, use of potent opioids, failed attempts at enteral nutrition, and, as a protective one, energy provided in PN. Conclusions: the factors related to mortality in hospitalized adult patients who required PN were mainly severity and comorbidities, but several other important factors were also relevant and could be modified to maximize outcomes in these patients.

Introducción: Objetivo: valorar los factores relacionados con la mortalidad en una cohorte de pacientes adultos hospitalizados que recibieron nutrición parenteral (NP) atendiendo a sus características, procedimientos, parámetros nutricionales y complicaciones. Métodos: estudio retrospectivo realizado en un hospital universitario de 400 camas. Se incluyeron todos los pacientes adultos que recibieron ≥ 4 días de NP en un periodo de 24 meses. Se excluyeron los pacientes con NP de largo plazo (> 90 días) o NP domiciliaria. La variable principal fue la mortalidad por cualquier causa en los 90 días posteriores al fin de la NP. Las variables independientes iniciales fueron los datos antropométricos y demográficos, el tipo de ingreso, la gravedad, la comorbilidad, los procedimientos médicos/quirúrgicos, los parámetros bioquímicos, el riesgo nutricional, otros parámetros nutricionales, las medicaciones y los eventos adversos durante la NP. Se realizó un análisis de supervivencia por el modelo de los riesgos proporcionales de Cox. Resultados: en total, 634 pacientes entraron en el estudio, de los cuales 140 (22,1 %) murieron. Los pacientes fueron principalmente: quirúrgicos 471 (74,3 %), hombres 393 (62,0 %) y de 69,0 (67,8-70,1) años de edad. La supervivencia de toda la cohorte fue de 74,0 (IC 95 %: 71,6-76,6) días. El modelo final incluyó 14 variables. La gravedad y la comorbilidad fueron las principales, pero también resultaron incluidas la dehiscencia de la sutura, la sepsis, los días con hiperglucemia, los intentos fallidos de nutrición enteral, el uso de opiáceos potentes y, como protector, la energía administrada en la NP. Conclusión: los factores relacionados con la mortalidad en estos pacientes con NP fueron principalmente la gravedad y la comorbilidad, pero otros factores también fueron relevantes y podrían ser modificados para maximizar los resultados en salud.

Cohort Multicenter Study on the Role of Medications in Parenteral Nutrition-Related Alteration of Liver Function Tests in Adults.

BACKGROUND: Our objective was to assess in non-critically-ill adult inpatients receiving parenteral nutrition (PN) the risk of developing liver function test (LFT) alterations when receiving concomitant possibly hepatotoxic medications or others reported to improve LFTs during PN. METHODS: A multicenter retrospective analysis of prospectively collected data was performed on patients receiving PN. Two groups were recruited: group LALT (patients with any LFT alterations during PN), and group NOLALT (patients without such alterations). Exclusion criteria were previous sepsis, shock, renal failure, hyperglycemia, LFT alteration, or biliopancreatic surgical procedures. Medications were classified into 2 categories: medications reported to improve LFTs during PN (n = 8) and possibly hepatotoxic medications (n = 54), including a subgroup of possibly highly hepatotoxic medications (n = 30). RESULTS: The study included 200 patients, 136 (68.0%) in the LALT group. The groups differed in the number of patients requiring surgical intervention ≤7 days before PN (LALT, 94 [69.1%]; NOLALT, 29 [45.3%]; P < .002) and those receiving possibly hepatotoxic medications (LALT, 126 [92.6%]; NOLALT, 45 [70.3%]; P < .001). Variables in the final Cox regression model were possibly hepatotoxic medications, odds ratio (OR) 3.310 (1.678-6.530); surgical intervention prior to PN, OR 1.861 (1.277-2.711); baseline triglyceridemia, OR 1.005 (1.001-1.009); and creatinine, OR 1.861 (1.043-3.323). CONCLUSIONS: Patients who received PN and concomitantly possibly hepatotoxic medications had a 3-fold risk of developing LFT alterations. Medications reported to improve LFTs had no effect. The use of possibly hepatotoxic medications during PN was associated with LFT alterations.

Successful dexrazoxane treatment of a potentially severe extravasation of concentrated doxorubicin.

Dexrazoxane is now authorized for the treatment of anthracycline extravasations. Several clinical cases of doxorubicin extravasation treated with dexrazoxane have been reported to date, but detailed cases have not been published. We report a case of a successful dexrazoxane treatment for a potentially severe extravasation of concentrated doxorubicin. We also describe objective outcome of this treatment, drug tolerance to dexrazoxane and long follow-up. A 29-year-old man diagnosed with Hodgkin's lymphoma was prescribed a regimen including 90 mg of doxorubicin in a 50 ml infusion using a reduced occlusion infusion pump. After this infusion, the patient complained of pain around the site of injection and presented a 10x6-cm swollen area with erythema and inflammation. A significant portion of doxorubicin was extravasated. Dexrazoxane was prescribed as an antidote. Side effects of dexrazoxane were restricted to reversible hematological toxicity, nausea, and vomiting. The next day, the inflammation of the extravasation area was reduced. On day 7, a painless mild induration in the extravasated area was the only remaining sign of the extravasation. On day 40, an arm nuclear magnetic resonance image showed no focal injuries. At 6-month follow-up, the patient has no sequelae. The two risk factors that could have increased the severity of the extravasation are the use of an infusion pump and the high drug concentration. Dexrazoxane proved to be effective and moderately well tolerated. A dexrazoxane stock in oncological facilities could help to promptly handle emergencies like this. Anthracyclines can be administered using reduced occlusion infusion pumps, but it seems preferable to always administer a free-running infusion to minimize accidents like this one.

[Stability: a factor to consider in antibiotic-lock solutions]. / La estabilidad como factor para considerar en las soluciones de sellado antibiótico.

Antibiotic-lock therapy (ALT) has been related to a reduction in the need for catheter withdrawal in patients with catheter-related infection. The stability of the antimicrobial solutions used in ALT has not been sufficiently investigated. A systematic literature review was performed to identify articles including studies on the stability of ALT solutions. Nine studies fulfilled the inclusion criteria requiring specific drug determination techniques, and no apparent drug alterations were observed. The main microorganisms studied were Staphylococcus spp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antibiotics included cefazolin, ceftazidime, ciprofloxacin, colistin, gentamicin, ticarcillin/clavulanate, and vancomycin in solution, administered alone or in combinations, with or without heparin. All solutions were fairly stable except for ciprofloxacin at a concentration of 10mg/mL. Few studies applied strict criteria to assess the stability of antibiotic solutions used in ALT; hence, the currently available data are limited. Therefore, it seems advisable to include appropriate stability studies in further research on the use of ALT.

[Differentiating clinical characteristics in bacteriemia caused by Enterococcus faecalis or Enterococcus faecium]. / Características clínicas diferenciales entre las bacteriemias por Enterococcus faecalis y Enterococcus faecium.

INTRODUCTION: Enterococci are responsible for severe infections, such as endocarditis and bacteremia. During recent decades, enterococcal infections have grown in importance because of the increasing number of cases. Knowledge of the factors predisposing to acquisition of infection by E. faecalis or E. faecium may be useful to improve the empirical treatment. METHODS: Retrospective study of patients diagnosed with enterococcal bacteremia and hospitalized over a 7-year period (January 2000-December 2006), analyzing demographic data, clinical and microbiological characteristics, antibiotic exposure, treatment, and outcome. To identify the predisposing factors for isolation of E. faecalis or E. faecium in a clinical specimen, we performed univariate comparisons between the 2 groups, and subsequently, multivariate logistic regression analysis. RESULTS: A total of 228 episodes of bacteremia were recorded, 168 caused by E. faecalis and 60 by E. faecium. All E. faecalis isolates were susceptible to ampicillin, but only 25% of E. faecium were ampicillin-susceptible. There was only 1 vancomycin-resistant isolate. The variables independently associated with acquisition of E. faecium bacteriemia were surgical ward admission (odds ratio [OR], 4.223; P=.001), >5 days of previous treatment with cephalosporins (OR, 2.564; P=.013), >5 days of carbapenems (OR, 2.652; P=.027), previous administration of penicillins (OR, 2.008; P=0.044), SAPS score >30 at admission (OR, 3.530; P=0.001), and hepatobiliary disease as a comorbid condition (OR, 3.754; P<0.001), CONCLUSION: Because of the differing susceptibility patterns of the enterococcal species studied, it is essential to know the factors predisposing to acquisition of infection by one or the other species to initiate adequate empirical treatment.

Propensity-Score Matched Comparative Study on Effects of Intravenous Human Serum Albumin Administration in Critically Ill Adult Patients Receiving Parenteral Nutrition.

BACKGROUND: The objective of this study was to assess the effect of intravenous human serum albumin administration (IV HSA) on nutrition markers, including non-serum-albumin plasma protein levels, in adult critically ill patients receiving parenteral nutrition (PN). METHODS: This was a retrospective study of prospectively collected data. Patients included in an initial cohort were patients who initiated IV HSA within 24 hours of start of PN. A second cohort who did not received IV HSA during PN was manually selected, matching several variables. Subsequently, both cohorts were propensity-score matched, resulting in 2 final cohorts: the cohort receiving IV HSA (ALB) and the cohort not receiving IV HSA (NOALB). RESULTS: A total of 42 patients, 21 in each cohort, entered the study. Both cohorts were similar in demographics, anthropometrics, comorbidities, diagnoses, PN composition, and severity of the disease, biochemistry, and nutrition markers. Patients in the ALB cohort received IV HSA at a dose of 30.0 g/day during 5 days. The ALB cohort presented higher values of final serum albumin level and serum albumin level change from baseline, but also presented lower values of final non-serum-albumin plasma protein levels and their change and lower final prealbumin. In addition, bilirubin in the ALB cohort increased, whereas it decreased in the NOALB cohort. CONCLUSION: Patients receiving IV HSA and PN for several days increased serum albumin level, but decreased non-serum-albumin plasma protein levels. In addition, bilirubin clearance could be slightly impaired in these patients.

Multicenter study of parenteral nutrition in non-critically ill elderly patients compared to younger patients - Study IAIOS-PN (Incidence and Assessment of Iatrogenesis in Older Subjects receiving Parenteral Nutrition).

OBJECTIVE: this study assessed the incidence of hyperglycemia, hypertriglyceridemia, and liver function test (LFT) alterations among patients older and younger than 65 years receiving parenteral nutrition (PN). A secondary objective was to compare the incidence of any of these three events. MATERIAL AND METHODS: inclusion criteria were non-critically ill adult inpatients receiving PN for ≥ 7 days in 15 hospitals in Spain. Exclusion criteria were hyperglycemia, hypertriglyceridemia, LFT alterations, sepsis, shock, pancreatic/hepatobiliary surgery, renal failure, diabetes mellitus (DM) type 1, insulin-treated DM type 2, acute DM complications, or obesity prior to PN. Patients were classified into groups YOUNG (aged 35-64) and OLD (aged 65-95). RESULTS: this study recruited 200 patients. Group YOUNG included 63 (31.5%) patients and OLD, 137 (68.5%). Hyperglycemia appeared in 37 (18.5%) patients, eight (12.7%) in group YOUNG and 29 (21.2%) in group OLD (p = 0.174). Hypertriglyceridemia appeared in only one (0.7%) patient. LFT alterations appeared in 141 (70.5%) patients, 44 (69.8%) in group YOUNG and 97 (70.8%) in group OLD (p = 1.000). The model for hyperglycemia included DM type 2, previous surgical procedure, and use of hyperglycemia-inducing medications. The model for LFT alteration included previous surgical procedure, amount of lipids and amino acids, medications causing LFT alterations and a trend for age group. The model for any event included surgical procedure, DM type 2, and medications causing alterations. CONCLUSION: patients of ≥ 65 years receiving PN had similar incidences of hyperglycemia, hypertriglyceridemia, and LFT alterations as younger patients. Additionally, older patients had trends toward lower LFT alterations.

Effects unrelated to anti-inflammation of lipid emulsions containing fish oil in parenteral nutrition for adult patients.

Several reviews and meta-analyses on modulated inflammatory and immunologic responses after the administration of omega-3 polyunsaturated fatty acids (PUFAs) in different diseases and conditions have been published. However, omega-3 PUFAs exert several other actions which are not directly related to immunologic or inflammatory responses. The aim of this paper was to review the effects which are not directly related to immunologic and inflammatory responses of intravenous lipid emulsions (IVLEs) containing fish oil (FO) in parenteral nutrition (PN) for adult patients. IVLEs containing FO could have a role in the prevention of alterations in liver enzyme tests (LETs) or PN-associated liver disease (PNALD). Studies using FO doses of ≥ 0.150 mg/kg/day or IVLEs with high FO concentration reported more positive results than those with lower doses. Once PNALD was developed, the use of IVLEs exclusively composed of FO at doses of 0.25-1 g of FO/kg/day for several weeks could attenuate or even eradicate cholestasis and liver alteration. IVLEs containing FO seemed to have faster blood clearance, and this could be beneficial for some patients. Some studies also suggested a possible improvement of respiratory function by the administration of these IVLEs. In general, IVLEs containing FO were safe. Their use did not increase oxidative stress but, in contrast, increased plasma tocopherol content. They did not alter insulin sensitivity or glycemic control, and studies have found no relevant clinical effect on platelet aggregation or hemostasis. In conclusion, the use of IVLEs containing FO in PN may be beneficial with regard to older IVLEs, in addition to the modulation of systemic inflammation response.

New Strategy to Reduce Hypertriglyceridemia During Parenteral Nutrition While Maintaining Energy Intake.

BACKGROUND: Hypertriglyceridemia is a frequent metabolic complication associated with fat administration in parenteral nutrition (PN). No clear guidelines have been published on how to proceed once hypertriglyceridemia has been detected. A new strategy could be to substitute the initial fat emulsion with another emulsion with faster clearance. Our objective was to determine the effectiveness in reducing triglyceridemia values, maintaining the caloric intake, and improving nutrition parameters in patients who had moderate hypertriglyceridemia during PN when an olive oil-based fat emulsion (OOFE) was substituted with a multiple-source oil fat emulsion (MOFE). We also assessed the safety of this substitution in hepatic and glycemic profiles. MATERIALS AND METHODS: We performed a retrospective, observational study that included 38 adult patients to whom OOFE in PN was substituted with MOFE when moderate hypertriglyceridemia (≥250-400 mg/dL) was detected. RESULTS: Triglyceridemia values decreased in 36 (94.7%) patients. The mean reduction was 71 (88-22) mg/dL. Fat load was slightly reduced after substitution (-0.14 [-0.23 to 0] g/kg/d; P < .001), but total caloric intake increased from 22.5 (19.7-25.1) to 23.1 (19.8-26.8) kcal/kg/d (P = .053). After substitution, nutrition parameters improved, liver parameters remained unchanged, and insulin requirements increased. CONCLUSION: The substitution of OOFE with MOFE in patients with moderate hypertriglyceridemia during PN resulted in a reduction in triglyceridemia values of about 70 mg/dL. That allowed maintaining the caloric intake and improved nutrition parameters without affecting the hepatic profile. For some patients, insulin requirements increased moderately.

[Estimation of hospital costs of colorectal cancer in Catalonia (Spain)]. / Estimación del coste hospitalario del cáncer colorrectal en Cataluña.

OBJECTIVE: To assess the hospital cost associated with colorectal cancer (CRC) treatment by stage at diagnosis, type of cost and disease phase in a public hospital. METHODS: A retrospective analysis was conducted of the hospital costs associated with a cohort of 699 patients diagnosed with CRC and treated for this disease between 2000 and 2006 in a teaching hospital and who had a 5-year follow-up from the time of diagnosis. Data were collected from clinical-administrative databases. Mean costs per patient were analysed by stage at diagnosis, cost type and disease phase. RESULTS: The mean cost per patient ranged from 6,573 Euros for patients with a diagnosis of CRC in situ to 36,894 € in those diagnosed in stage III. The main cost components were surgery-inpatient care (59.2%) and chemotherapy (19.4%). Advanced disease stages were associated with a decrease in the relative weight of surgical and inpatient care costs and an increase in chemotherapy costs. CONCLUSIONS: This study provides the costs of CRC treatment based on clinical practice, with chemotherapy and surgery accounting for the major cost components. This cost analysis is a baseline study that will provide a useful source of information for future studies on cost-effectiveness and on the budget impact of different therapeutic innovations in Spain.