Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial.

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48-96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient.

OBJECTIVE: Critical illness is associated with the generation of oxygen free radicals and low endogenous antioxidant capacity leading to a condition of oxidative stress. We investigated whether supplementing critically ill patients with antioxidants, trace elements, and vitamins improves their survival. METHODS: We searched four bibliographic databases from 1980 to 2003 and included studies that were randomized, reported clinically important endpoints in critically ill patients, and compared various trace elements and vitamins to placebo. RESULTS: Eleven articles met the inclusion criteria. When the results of all the trials were aggregated, overall antioxidants were associated with a significant reduction in mortality [Risk Ratio (RR) 0.65, 95% confidence intervals (CI) 0.44-0.97, p=0.03] but had no effect on infectious complications. Studies that utilized a single trace element were associated with a significant reduction in mortality [RR 0.52, 95% CI 0.27-0.98, p=0.04] whereas combined antioxidants had no effect. Studies using parenteral antioxidants were associated with a significant reduction in mortality [RR 0.56, 95% CI 0.34-0,92, p=0.02] whereas studies of enteral antioxidants were not. Selenium supplementation (alone and in combination with other antioxidants) may be associated with a reduction in mortality [RR 0.59, 95% CI 0.32-1.08, p=0.09] while nonselenium antioxidants had no effect on mortality. CONCLUSIONS: Trace elements and vitamins that support antioxidant function, particularly high-dose parenteral selenium either alone or in combination with other antioxidants, are safe and may be associated with a reduction in mortality in critically ill patients.

Is glutamine deficiency the link between inflammation, malnutrition, and fatigue in cancer patients?

PURPOSE: Evaluation of potential associations between plasma glutamine levels and the incidence of cancer related fatigue, physical performance, poor nutritional status, and inflammation in patients with solid tumors. STUDY DESIGN: Mono-center cross-sectional study recruiting 100 (34 women) consecutive patients (September 2009-March 2011; ≥18 y) with solid tumors and causal tumor therapy. METHODOLOGY: Fasting venous blood was harvested for routine clinical chemistry, amino acid (HPLC) and inflammation marker analyses. Clinical assessments included global, physical, affective and cognitive fatigue (questionnaire) and Karnofsky performance status. Nutritional status was evaluated using bioelectrical impedance analysis, the Prognostic Inflammatory and Nutritional Index and plasma protein levels. Regression analyses were performed to correlate continuous variables with plasma glutamine (95% confidence intervals). RESULTS: Nutritional status was impaired in 19% of the patients. Average plasma glutamine concentration (574.0 ± 189.6 µmol/L) was within normal range but decreased with impaired physical function. Plasma glutamine was linked to the ratio extracellular to body cell mass (p < 0.044), CRP (p < 0.001), physical (p = 0.014), affective (p = 0.041), and global fatigue (p = 0.030). Markers of inflammation increased with low physical performance. CONCLUSIONS: The data support our working hypothesis that in cancer patients systemic inflammation maintains a catabolic situation leading to malnutrition symptoms and glutamine deprivation, the latter being associated with cancer related fatigue.

Survey on structure and performance of nutrition-support teams in Germany.

BACKGROUND & AIMS: Interdisciplinary nutrition-support teams (NSTs) can improve the efficacy of clinical nutrition. The purpose of this survey was to investigate the prevalence, and structure of German NSTs. METHOD: Hospitals in Germany with more that 250 beds were screened for the existence of NSTs. Eligible NSTs were interviewed about structural characteristics, administration of clinical nutrition and quality control in a face-to-face manner using a standardised questionnaire. RESULTS: A total of 47 NSTs existed in Germany revealing a prevalence of 5.6%. Their main activities were creating nutritional regimens (100%), education (98%) and monitoring nutrition therapy (96%). Twenty-two of NST-physicians (50%) had a specific education as compared to 20.9% NST-nurses and 24% NST-dietitians. Only 12.7% of physicians and 17% of dieticians in comparison to 55.3% of nurses received funding support. Improvement of clinical nutrition by means of increased use of enteral nutrition and special diets was indicated by 72%, 23%, respectively. Some NSTs indicated a reduction of complications (38.3%) and cost-saving (34%) since their establishment. CONCLUSIONS: There is a low prevalence of interdisciplinary NSTs in Germany. Standards of practice, development of guidelines in clinical nutrition and better documentation in NSTs are necessary. Special efforts should be aimed at education of NST members and financing of teams.

Intravenous free and dipeptide-bound glutamine maintains intestinal microcirculation in experimental endotoxemia.

OBJECTIVE: The administration of glutamine (Gln), which is depleted in critical illness, is associated with an improvement of gut metabolism, structure, and function. The aim of the present study was to evaluate the effects of intravenous Gln and its galenic formulation, l-alanyl-l-glutamine dipeptide (AlaGln), on the intestinal microcirculation during experimental endotoxemia using intravital fluorescence microscopy. Gln or AlaGln administration was performed as pretreatment or post-treatment, respectively. To identify further the underlying mechanisms, amino acid levels were studied. METHODS: Sixty male Lewis rats were randomly divided into six groups (n = 10/group): control, LPS (lipopolysaccharide 5 mg/kg intravenously), Gln/LPS (LPS animals pretreated with Gln 0.75 g/kg Gln intravenously), AlaGln/LPS (LPS animals pretreated with AlaGln intravenously, 0.75 g/kg Gln content), LPS/Gln (LPS animals post-treated with Gln 0.75 g/kg intravenously), and LPS/AlaGln (LPS animals post-treated with AlaGln intravenously, 0.75 g/kg Gln content). Two hours after the endotoxin challenge, the microcirculation of the terminal ileum was studied using intravital fluorescence microscopy. Blood samples were drawn at the beginning, during, and the end of the experiment to determine the amino acid levels. RESULTS: The Gln and AlaGln pre- and post-treatment, respectively, prevented the LPS-induced decrease in the functional capillary density of the intestinal muscular and mucosal layers (P < 0.05). The number of adherent leukocytes in the submucosal venules was significantly attenuated after the Gln and AlaGln pre- and post-treatment (P < 0.05). CONCLUSION: The Gln and AlaGln administrations improved the intestinal microcirculation by increasing the functional capillary density of the intestinal wall and decreasing the submucosal leukocyte activation.

REducing Deaths due to OXidative Stress (The REDOXS Study): Rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients.

Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2 x 2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.