Influence of n-3 polyunsaturated fatty acids enriched lipid emulsions on nosocomial infections and clinical outcomes in critically ill patients: ICU lipids study.

OBJECTIVE: n-3 polyunsaturated fatty acids (contained in fish oil) have been shown to beneficially influence infection rate and clinical outcomes in surgical patients probably due to their immunomodulatory action. In contrast, study results of fish oil administration in critically ill patients are controversial. The aim of this study was to investigate the effects of n-3 polyunsaturated fatty acids on the prevalence of nosocomial infections and clinical outcomes in medical and surgical critically ill patients. DESIGN: Prospective, multicenter, randomized, comparative, double-blind study. SETTING: Seventeen Spanish ICUs during 4 years. SUBJECTS: A total of 159 medical and surgical intensive care patients with Acute Physiology and Chronic Health Evaluation II score more than or equal to 13, expected to require total parenteral nutrition for at least 5 days. INTERVENTIONS: Patients received total parenteral nutrition prepared either with a lipid emulsion containing 10% fish oil or a fish oil-free lipid emulsion. The prevalence of nosocomial infections was detected during 28 days of ICU stay. Patients were followed 6 months after discharge from the ICU for length of hospital stay, hospital mortality, and 6-month mortality. MEASUREMENTS AND MAIN RESULTS: The number of patients with nosocomial infections was significantly reduced in the fish oil-receiving group (21.0% vs 37.2%, p = 0.035) and the predicted time free of infection was prolonged (21 ± 2 vs 16 ± 2 d, p = 0.03). No significant differences were detected for ICU, hospital, and 6-month mortality. CONCLUSIONS: The results show that administration of n-3 polyunsaturated fatty acids reduces the risk of nosocomial infections and increases the predicted time free of infections in critically ill medical and surgical patients. The administration of n-3 polyunsaturated fatty acids was safe and well tolerated.

Diabetes-specific enteral nutrition formula in hyperglycemic, mechanically ventilated, critically ill patients: a prospective, open-label, blind-randomized, multicenter study.

INTRODUCTION: Although standard enteral nutrition is universally accepted, the use of disease-specific formulas for hyperglycemic patients is still controversial. This study examines whether a high-protein diabetes-specific formula reduces insulin needs, improves glycemic control and reduces ICU-acquired infection in critically ill, hyperglycemic patients on mechanical ventilation (MV). METHODS: This was a prospective, open-label, randomized (web-based, blinded) study conducted at nine Spanish ICUs. The patient groups established according to the high-protein formula received were: group A, new-generation diabetes-specific formula; group B, standard control formula; group C, control diabetes-specific formula. Inclusion criteria were: expected enteral nutrition ≥5 days, MV, baseline glucose >126 mg/dL on admission or >200 mg/dL in the first 48 h. Exclusion criteria were: APACHE II ≤10, insulin-dependent diabetes, renal or hepatic failure, treatment with corticosteroids, immunosuppressants or lipid-lowering drugs and body mass index ≥40 kg/m(2). The targeted glucose level was 110-150 mg/dL. Glycemic variability was calculated as the standard deviation, glycemic lability index and coefficient of variation. Acquired infections were recorded using published consensus criteria for critically ill patients. Data analysis was on an intention-to-treat basis. RESULTS: Over a 2-year period, 157 patients were consecutively enrolled (A 52, B 53 and C 52). Compared with the standard control formula, the new formula gave rise to lower insulin requirement (19.1 ± 13.1 vs. 23.7 ± 40.1 IU/day, p <0.05), plasma glucose (138.6 ± 39.1 vs. 146.1 ± 49.9 mg/dL, p <0.01) and capillary blood glucose (146.1 ± 45.8 vs. 155.3 ± 63.6 mg/dL, p <0.001). Compared with the control diabetes-specific formula, only capillary glucose levels were significantly reduced (146.1 ± 45.8 vs. 150.1 ± 41.9, p <0.01). Both specific formulas reduced capillary glucose on ICU day 1 (p <0.01), glucose variability in the first week (p <0.05), and incidences of ventilator-associated tracheobronchitis (p <0.01) or pneumonia (p <0.05) compared with the standard formula. No effects of the nutrition formula were produced on hospital stay or mortality. CONCLUSIONS: In these high-risk ICU patients, both diabetes-specific formulas lowered insulin requirements, improved glycemic control and reduced the risk of acquired infections relative to the standard formula. Compared with the control-specific formula, the new-generation formula also improved capillary glycemia. TRIAL REGISTRATION: Clinicaltrials.gov NCT1233726 .

Nutritional recommendations in hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation is a procedure necessitating the administration of high-dose chemoradiotherapy. This therapy may induce aggressive disruptions that can lead to special nutritional and metabolic conditions. These patients are at an increased risk for malnutrition in the phase before transplantation and afterward. Artificial nutrition, total parenteral nutrition in particular, is provided to patients undergoing hematopoietic stem cell transplantation to help minimize adverse nutritional consequences.

Liver dysfunction associated with artificial nutrition in critically ill patients.

INTRODUCTION: Liver dysfunction associated with artificial nutrition in critically ill patients is a complication that seems to be frequent, but it has not been assessed previously in a large cohort of critically ill patients. METHODS: We conducted a prospective cohort study of incidence in 40 intensive care units. Different liver dysfunction patterns were defined: (a) cholestasis: alkaline phosphatase of more than 280 IU/l, gamma-glutamyl-transferase of more than 50 IU/l, or bilirubin of more than 1.2 mg/dl; (b) liver necrosis: aspartate aminotransferase of more than 40 IU/l or alanine aminotransferase of more than 42 IU/l, plus bilirubin of more than 1.2 mg/dl or international normalized ratio of more than 1.4; and (c) mixed pattern: alkaline phosphatase of more than 280 IU/l or gamma-glutamyl-transferase of more than 50 IU/l, plus aspartate aminotransferase of more than 40 IU/l or alanine aminotransferase of more than 42 IU/l. RESULTS: Seven hundred and twenty-five of 3,409 patients received artificial nutrition: 303 received total parenteral nutrition (TPN) and 422 received enteral nutrition (EN). Twenty-three percent of patients developed liver dysfunction: 30% in the TPN group and 18% in the EN group. The univariate analysis showed an association between liver dysfunction and TPN (p < 0.001), Multiple Organ Dysfunction Score on admission (p < 0.001), sepsis (p < 0.001), early use of artificial nutrition (p < 0.03), and malnutrition (p < 0.01). In the multivariate analysis, liver dysfunction was associated with TPN (p < 0.001), sepsis (p < 0.02), early use of artificial nutrition (p < 0.03), and calculated energy requirements of more than 25 kcal/kg per day (p < 0.05). CONCLUSION: TPN, sepsis, and excessive calculated energy requirements appear as risk factors for developing liver dysfunction. Septic critically ill patients should not be fed with excessive caloric amounts, particularly when TPN is employed. Administering artificial nutrition in the first 24 hours after admission seems to have a protective effect.

[Eighth Jesús Culebras Lecture. Critical Care, nutrition and hyperglycemia: a close relationship]. / Octava Lección Jesús Culebras. Medicina Intensiva, nutrición e hiperglucemia: una relación muy estrecha.

Critically ill patients show a metabolic response to injury that affects carbohydrate metabolism, causing hyperglycemia and an increase in glycemic variability that makes the critically ill patient susceptible to infection, resulting in morbidity and mortality increase. Also, severe hypoglycemia was detected as a consequence of intensive insulin treatment that provokes deleterious effects in their clinical evolution, so a correct monitoring of plasma glucose would contribute to reduce morbidity and mortality. In critically ill patients, glucose metabolism is in allostasis stage as a consequence of metabolic stress, producing an increase in peripheral resistance to insulin that causes an imbalance with the pancreatic beta-cell function, increasing insulin secretion to maintain plasma glucose levels within normality ranges. Numerous studies have been published about treatments with insulin and glycemic variability, whereas there are very few about nutrometabolic treatment of hyperglycemia in critically ill patients. Of all of them we can conclude that it is always recommended to keep glucose levels under 180 mg/dl, and when possible, not over 150 mg/dl, establishing a lower range of 110-140 mg/dl. Moreover, tight glycemic control increases the risk of severe hypoglycemia (≤ 40 mg/dl) and its subsequent mortality, so we advise against it. Besides, glycemic variability has been independently associated with an increase of mortality in critically ill patients and, consequently, protocols should aim at avoiding it. Nutritional treatment with diabetes-specific diets not only improves hyperglycemic control and decreases insulin needs, but also decreases glycemic variability and could reduce the incidence of infectious complications. Therefore, they are recommended, at least during the first week of stay. Finally, diabetes seems to modulates the consequences of hyperglycemia in critically ill patients, so diabetic patients could benefit from a higher glycemic target than those without diabetes but with stress hyperglycemia.

Immunonutrition in the intensive care unit. A systematic review and consensus statement.

OBJECTIVE: To systematically review the effects of enteral nutrition with pharmaconutrients-enriched diets in critically ill patients and to establish recommendations for their use. DATA SOURCES: Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION: Randomized clinical trials of critically ill patients treated with enteral nutrition comparing diets enriched with pharmaconutrients vs not enriched diets were included. Infectious complications and outcome variables (days on mechanical ventilation, ICU and hospital length of stay and mortality) were evaluated. Studies were classified in four subgroups according to the patient's primary diagnosis: surgical, trauma, burned or medical. DATA EXTRACTION: A group of experts in methodology performed data extraction and statistical processes. A global analysis of the studies was done and also a separate study for each subgroup. Results of the meta-analysis were discussed within a 'clinical group' of clinicians with experience in the nutritional support of ICU patients, in order to find agreement about recommendations for the use of pharmaconutrients-enriched diets in critically ill patients. RESULTS: Independent review of 267 articles identified 26 relevant primary studies. Global results indicate that there was a reduction in infection rate in the pharmaconutrition group, considering the appreciated lower incidence in abdominal abscesses (OR: 0.26, CI: 0.12-0.55) (P=0.005), nosocomial pneumonia (OR: 0.54, CI: 0.35-0.84) (P=0.007) and bacteremia (OR: 0.45, CI: 0.35-0.84) (P=0.0002). Also, patients treated with pharmaconutrition diets have a reduction in time on mechanical ventilation (mean 2.25 days, CI: 0.5-3.9) (P=0.009), ICU length of stay (mean reduction of 1.6 days, CI: 1.9-1.2) (P<0.0001) and hospital length of stay (mean reduction of 3.4 days, CI: 4.0-2.7) (P<0.0001). No effects were appreciated on mortality (OR: 1.10, CI: 0.85-1.42) (P=0.5). Nevertheless, the separate analysis for each subgroup showed that the reported beneficial effects were not the same for each patient population. Also, the clinician panel of experts identifies several problems in the published data about enteral pharmaconutrition in critically ill patients. In spite of the subgroup differences and of the problems detected, the clinician group considered that the appreciated results could support a Grade B recommendation for the use of these formulas in ICU patients. CONCLUSIONS: Considering the beneficial effects and the absence of detrimental ones, the use of diets enriched with pharmaconutrients could be recommended in ICU patients requiring enteral feeding. Nevertheless, more investigation is needed in this field in order to find the more appropriate population of patients that can benefit from this nutritional therapy.

Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study.

We investigated the effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity and mortality in critically ill patients who developed systemic inflammatory response syndrome after an acute event. Eleven intensive care units in tertiary-care hospitals participated in a prospective, randomized, single blind, multicenter trial. Eighty-four patients with systemic inflammatory response syndrome of any etiology were randomly allocated to receive a glutamine-enriched enteral diet or a control diet without glutamine.Most patients received the planned caloric intake. The number of infected patients was smaller in the glutamine group than in the control group (11 versus 17 patients, P < 0.05), with a relative risk of 0.5 (95% confidence interval = 0.3-0.9). The most frequent infection was nosocomial pneumonia, with 11 (33%) patients in the control group and 6 (14%) in the glutamine group. There were no differences with respect to other infections, mortality, or length of stay. Intestinal permeability as assessed by the lactulose-mannitol test was unchanged in both groups.Glutamine-enriched enteral diets can decrease nosocomial infections in patients with systemic inflammatory response syndrome.

[Management of parenteral nutrition in intensive care units in Spain]. / Manejo de la nutrición parenteral en las Unidades de Cuidados Intensivos en España.

INTRODUCTION AND OBJECTIVES: some relevant aspects related to parenteral nutrition in the Spanish ICUs are still unclear. These aspects include: caloric and protein intake, total volume, glycemic control, the type of lipid emulsion used or the comparison of different formulations. Our objective is to know the clinical practice patterns of artificial nutrition therapeutics, particularly of parenteral nutrition in the Spanish ICUs. MATERIAL AND METHODS: twelve representative ICU's participated in a nutrition survey from January to March 2012. The survey was divided in two sections: A) Management of artificial nutritional support in critically ill patients and B) Assessment of a new parenteral nutrition formulation adapted to critically ill patients. The following information was collected: percentage of patients receiving artificial nutrition; availability of enteral formulations; types of lipid emulsions; calories, amino acids and lipids supplied; addition of glutamine, vitamins and trace elements; management of volume and hyperglycemia; and comparative data between patients receiving the new formulation vs. standard formulations: glycemic control, assessment of hepatic function and infectious complications as well as the intake of total calories, proteins, volume and insulin supplied. RESULTS: The average number of hospital beds and ICU beds is 780 and 25 respectively; the average number of patients admitted in the ICU is 950 per year. 49% were medical patients, 31% surgical patients and 20% trauma patients. 59.75% of patients required artificial nutrition (AN), of which, 58.7% required enteral nutrition (EN), 16% total parenteral nutrition (TPN); and 25.3% suplementary parenteral nutrition (SPN). When EN was contraindicated, 83.3% of patients were started on early TPN (24 hours) and if EN was not sufficient, 66.7% were started on SPN within 48 hours. Regarding prescribers usual practice, 50% tried to reduce volume of PN and 100% of them had an insulin infusion protocol. 39% of prescribers recommended high-protein, low-volume and low-glucose TPN; 42% prescribe TPN with SMOF (soybean, MCT, olive and fish oil); and 33% with OOBE (olive oil based emulsion) as lipid emulsion. 92% added glutamine. 60% considered that the new formulation may be indicated for sepsis, trauma, burn patients and MOF (multiple organ failure) and the 30% would use it as a routine therapy at the time of admission. 40% considered that insulin requirements were reduced; 50% claimed better volume management and 60% highlighted the protein/volume ratio. Attending to patient outcome, patients receiving the specific formulation have less affected hepatic function, higher protein intake and lower volume infusion but no significant differences were observed and they required less insulin dosage (p = 0.07). CONCLUSIONS: In the twelve ICUs included in the survey, the clinical practice patterns related to parenteral nutrition management are adapted to the guidelines of scientific societies such as the Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC), the Spanish Society of Parenteral and Enteral Nutrition (SENPE) and the European Society for Clinical Nutrition and Metabolism (ESPEN). The new formulations designed for critically ill patients may be indicated for these conditions.

Introducción y objetivos: No se sabe con exactitud aspectos de relevancia en nutrición parenteral como aportes calórico-proteicos, volumen total, control de glucemia, tipo de emulsión lipídica o comparación de diferentes fórmulas, en las UCIs españolas. Planteamos como objetivo conocer los patrones de práctica clínica habitual en la terapéutica con nutrición artificial, fundamentalmente parenteral, en dichas UCIs. Material y métodos: Participaron doce UCIs representativas, de enero a marzo de dos mil doce, para la realización de una encuesta nutricional. La encuesta se dividió en dos apartados : A) Manejo del soporte nutricional artificial en el paciente grave y B) Valoración de una nueva fórmula de nutrición parenteral adaptada al paciente grave. Se recogió: porcentaje de pacientes con nutrición artificial; disponibilidad de fórmulas enterales; tipos de emulsiones lipídicas; calorías, aminoácidos y lípidos aportados; adición de glutamina, vitaminas y oligoelementos; manejo del volumen y de la hiperglucemia y datos comparativos de pacientes con la nueva formulación frente a fórmulas de uso habitual: control glucémico, afectación hepática y complicaciones infecciosas, así como aportes de calorías totales, proteínas, volumen e insulina administrada. Resultados: La media de camas hospitalarias es de 780 y de UCI de 25, con una media de ingresos de 950 pacientes/año. Un 49% son pacientes médicos, 31% quirúrgicos y 20% traumatológicos. El 59,75% precisaron nutrición artificial (NA). De ellos, 58,7% nutrición enteral (NE), 16% nutrición parenteral total (NPT) y 25,3% nutrición parenteral complementaria (NPC). Ante NE contraindicada, el 83,3% inicia NPT precoz (24 horas) y ante NE insuficiente el 66,7% inicia NPC en 48 horas. En relación con la práctica habitual de los prescriptores, un 50% intenta reducción de volumen y el 100% dispone de protocolo de infusión de insulina. Un 39% recomiendan NPT hiperproteica, baja en volumen y en glucosa, el 42% con SMOF (Soja, MCT, Oliva, Pescado) y el 33% con EBAO (Emulsiones Basadas en Aceite de Oliva) como emulsión lipídica. El 92% adiciona glutamina. Un 60% considera que la nueva fórmula puede estar indicada en sepsis, trauma, quemados y FMO (Fracaso Multiorgánico) y un 30% la utilizaría de rutina al ingreso. Un 40% considera que disminuye las necesidades de insulina, 50% un mejor manejo del volumen y un 60% destaca la relación proteínas/volumen. Evolutivamente, los pacientes con fórmula específica tienen menor afectación hepática, mayor aporte proteico y menor aporte de volumen, sin diferencias significativas, y precisaron menos dosis de insulina (p = 0,07). Conclusiones: En las doce UCIs seleccionadas, los patrones de práctica clínica en el manejo de la nutrición parenteral se adaptan a las recomendaciones de sociedades científicas como la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC), Sociedad Española de Nutrición Parenteral y Enteral (SENPE) y European Society for Clinical Nutrition and Metabolism (ESPEN). Las nuevas fórmulas diseñadas para el paciente grave pueden tener indicaciones en estas patologías.

Effect of an enteral diet enriched with eicosapentaenoic acid, gamma-linolenic acid and anti-oxidants on the outcome of mechanically ventilated, critically ill, septic patients.

BACKGROUND & AIMS: To assess the effect of an enteral diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and anti-oxidants on the incidence of organ dysfunction and nosocomial infections in septic patients with acute lung injury or acute respiratory distress syndrome (ARDS) compared with a standard enteral diet. METHODS: This prospective, randomized, open-label study was performed in 11 Spanish intensive care units (ICU). Adult patients with sepsis and acute lung injury or ARDS were randomly allocated to receive either an EPA-GLA diet or a control diet. RESULTS: Of the 198 patients that were eligible, 160 were randomized and 132 were studied. Patient demographics, APACHE II and SOFA scores, and nutritional variables on admission were similar between the EPA-GLA diet and control diet groups. The EPA-GLA diet group showed a trend toward a decreased SOFA score, but it was not significant. No differences were observed in the PaO(2)/FiO(2) ratio or the days on mechanical ventilation between the groups. Incidence of infections was similar in the groups. The control group stayed longer in the ICU than the EPA-GLA diet group (16 vs. 18; p = 0.02). CONCLUSIONS: A diet enriched with EPA, GLA, and anti-oxidants does not improve gas exchange or decrease the incidence of novel organ failures in critically ill septic patients with acute lung injury or ARDS. Patients treated with the EPA-GLA diet stayed in the ICU for less time, but we did not find any differences in infectious complications.

Multicenter, prospective, randomized, single-blind study comparing the efficacy and gastrointestinal complications of early jejunal feeding with early gastric feeding in critically ill patients.

OBJECTIVE: To compare the incidence of enteral nutrition-related gastrointestinal complications, the efficacy of diet administration, and the incidence of nosocomial pneumonia in patients fed in the stomach or in the jejunum. DESIGN: Prospective, randomized multicenter study. SETTING: Intensive care units (ICUs) in 11 teaching hospitals. PATIENTS: Critically ill patients who could receive early enteral nutrition more than 5 days. INTERVENTIONS: Enteral nutrition was started in the first 36 hrs after admission. One group was fed with a nasogastric tube (GEN group) and the other in the jejunum through a dual-lumen nasogastrojejunal tube (JEN group). MEASUREMENTS AND MAIN RESULTS: Gastrointestinal complications were previously defined. The efficacy of diet administration was calculated using the volume ratio (expressed as the ratio between administered and prescribed volumes). Nosocomial pneumonia was defined according the Centers for Disease Control and Prevention's definitions. One hundred ten patients were included (GEN: 51, JEN: 50). Both groups were comparable in age, gender, Acute Physiology and Chronic Health Evaluation II, and Multiple Organ Dysfunction Score. There were no differences in feeding duration, ICU length of stay, or mortality (43% vs. 38%). The JEN group had lesser gastrointestinal complications (57% vs. 24%, p <.001), mainly because of a lesser incidence of increased gastric residuals (49% vs. 2%, p <.001). Volume ratio was similar in both groups. A post hoc analysis showed that the JEN group had a higher volume ratio at day 7 than the GEN group (68% vs. 82%, p <.03) in patients from ICUs with previous experience in jejunal feeding. Both groups had a similar incidence of nosocomial pneumonia (40% vs. 32%). CONCLUSIONS: Gastrointestinal complications are less frequent in ICU patients fed in the jejunum. Nevertheless, it seems to be a necessary learning curve to achieve better results with a postpyloric access. Early enteral nutrition using a nasojejunal route seems not to be an efficacious measure to decrease nosocomial pneumonia in critically ill patients.