Space GlucoseControl system for blood glucose control in intensive care patients--a European multicentre observational study.

BACKGROUND: Glycaemia control (GC) remains an important therapeutic goal in critically ill patients. The enhanced Model Predictive Control (eMPC) algorithm, which models the behaviour of blood glucose (BG) and insulin sensitivity in individual ICU patients with variable blood samples, is an effective, clinically proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocols. eMPC has been integrated into the B.Braun Space GlucoseControl system (SGC), which allows direct data communication between pumps and microprocessor. The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU settings and with various nutritional protocols. METHODS: The study endpoints were the percentage of time the BG was within the target range 4.4 - 8.3 mmol.l(-1), the frequency of hypoglycaemic episodes, adherence to the advice of the SGC and BG measurement intervals. BG was monitored, and insulin was given as a continuous infusion according to the advice of the SGC. Nutritional management (enteral, parenteral or both) was carried out at the discretion of each centre. RESULTS: 17 centres from 9 European countries included a total of 508 patients, the median study time was 2.9 (1.9-6.1) days. The median (IQR) time-in-target was 83.0 (68.7-93.1) % of time with the mean proposed measurement interval 2.0 ± 0.5 hours. 99.6% of the SGC advices on insulin infusion rate were accepted by the user. Only 4 episodes (0.01% of all BG measurements) of severe hypoglycaemia <2.2 mmol.l(-1) in 4 patients occurred (0.8%; 95% CI 0.02-1.6%). CONCLUSION: Under routine conditions and under different nutritional protocols the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01523665.

The effect of L-alanyl-L-glutamine dipeptide supplemented total parenteral nutrition on infectious morbidity and insulin sensitivity in critically ill patients.

OBJECTIVE: The aim of this study was to assess the clinical efficacy of alanine-glutamine dipeptide-supplemented total parenteral nutrition defined by the occurrence of nosocomial infections. Secondary parameters included Sequential Organ Failure Assessment score, hyperglycemia and insulin needs, intensive care unit and hospital length of stay, and 6-month mortality. DESIGN: Multicenter, prospective, double-blind, randomized trial. SETTING: Twelve intensive care units at Spanish hospitals. PATIENTS: One hundred twenty-seven patients with Acute Physiology and Chronic Health Evaluation II score >12 and requiring parenteral nutrition for 5-9 days. INTERVENTION: Patients were randomized to receive an isonitrogenous and isocaloric total parenteral nutrition or alanine-glutamine dipeptide-supplemented total parenteral nutrition. Nutritional needs were calculated: 0.25 g N/kg(-1)/d(-1) and 25 kcal/kg(-1)/d(-1). The study group received 0.5 g/kg(-1)/d(-1) of glutamine dipeptide and the control total parenteral nutrition group a similar amount of amino acids. Hyperglycemia was controlled applying an intensive insulin protocol with a target glycemia of 140 mg/dL. MEASUREMENTS AND MAIN RESULTS: The two groups did not differ at inclusion for the type and severity of injury or the presence of sepsis or septic shock. Caloric intake was similar in both groups. Preprotocol analysis showed that treated patients with alanine-glutamine dipeptide-supplemented total parenteral nutrition had lesser nosocomial pneumonia, 8.04 vs. 29.25 episodes-‰ days of mechanical ventilation (p = .02), and urinary tract infections, 2.5 vs. 16.7 episodes-‰ days of urinary catheter (p = .04). Intensive care unit, hospital, and 6-month survival were not different. Mean plasmatic glycemia was 149 ± 46 mg/dL in the alanine-glutamine dipeptide-supplemented total parenteral nutrition group and 155 ± 51 mg/dL in the control total parenteral nutrition group (p < .04), and mean hourly insulin dose was 4.3 ± 3.3 IU in the alanine-glutamine dipeptide-supplemented total parenteral nutrition group and 4.7 ± 3.7 IU in control total parenteral nutrition group (p < .001). Multivariate analysis showed a 54% reduction of the amount of insulin for the same levels of glycemia in the alanine-glutamine dipeptide-supplemented total parenteral nutrition group. CONCLUSIONS: Total parenteral nutrition supplemented with alanine-glutamine in intensive care unit patients is associated with a reduced rate of infectious complications and better glycemic control.

Caloric intake and liver dysfunction in critically ill patients.

PURPOSE OF REVIEW: Despite increasing evidence that critically ill patients have lower energy requirements than expected, most guidelines continue to recommend elevated caloric requirements in these patients, particularly in septic patients. This practice leads to liver dysfunction when artificial nutrition is employed and worsens the prognosis of these patients. This review is focused on recent developments in the pathogenesis of artificial nutrition associated liver dysfunction in critically ill patients. RECENT FINDINGS: The liver plays a pivotal role in managing nutritional substrates, and it is involved in the inflammatory response to injury and sepsis. The landmark phenomenon is insulin resistance and changes in the metabolic fates of glucose and fat. Glucose and lipids can act as toxics synergistically with inflammation to induce liver dysfunction. There are experimental evidences that insulin resistance in critically ill patients can share the same biochemical mechanisms and metabolic fates involved in insulin resistance of type 2 diabetes mellitus and metabolic syndrome. Furthermore, steatosis is also a common feature in both clinical pictures SUMMARY: The pathogenesis of artificial nutrition associated with liver dysfunction is related to overfeeding and sepsis with a pathophysiology, similar to metabolic syndrome and type 2 diabetes. Changing nutritional strategies and adding new drugs will prevent, in part, liver dysfunction in these patients.

Nutritrauma: A Key Concept for Minimising the Harmful Effects of the Administration of Medical Nutrition Therapy.

Critically ill patients often require life support measures such as mechanical ventilation or haemodialysis. Despite the essential role of nutrition in patients' recovery, the inappropriate use of medical nutrition therapy can have deleterious effects, as is the case with the use of respiratory, circulatory, or renal support. To increase awareness and to monitor the effects of inappropriate medical nutrition therapy, we propose to introduce the concept of nutritrauma in clinical practice, defined as metabolic adverse events related to the inappropriate administration of medical nutrition therapy or inadequate nutritional monitoring.

Lipids in the intensive care unit: Recommendations from the ESPEN Expert Group.

This article summarizes the presentations given at an ESPEN Workshop on "Lipids in the ICU" held in Tel Aviv, Israel in November 2014 and subsequent discussions and updates. Lipids are an important component of enteral and parenteral nutrition support and provide essential fatty acids, a concentrated source of calories and building blocks for cell membranes. Whilst linoleic acid-rich vegetable oil-based enteral and parenteral nutrition is still widely used, newer lipid components such as medium-chain triglycerides and olive oil are safe and well tolerated. Fish oil (FO)-enriched enteral and parenteral nutrition appears to be well tolerated and confers additional clinical benefits, particularly in surgical patients, due to its anti-inflammatory and immune-modulating effects. Whilst the evidence base is not conclusive, there appears to be a potential for FO-enriched nutrition, particularly administered peri-operatively, to reduce the rate of complications and intensive care unit (ICU) and hospital stay in surgical ICU patients. The evidence for FO-enriched nutrition in non-surgical ICU patients is less clear regarding its clinical benefits and additional, well-designed large-scale clinical trials need to be conducted in this area. The ESPEN Expert Group supports the use of olive oil and FO in nutrition support in surgical and non-surgical ICU patients but considers that further research is required to provide a more robust evidence base.

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.

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.

Safety and metabolic tolerance of a concentrated long-chain triglyceride lipid emulsion in critically ill septic and trauma patients.

BACKGROUND: A concentrated fat emulsion (Intralipid 30%) with a phospholipid/triglyceride ratio of 0.04 was tested for clinical tolerance and metabolic effects in the short-term parenteral nutrition of septic and trauma critically ill patients and compared with Intralipid 20% (phospholipid/triglyceride ratio of 0.06). METHODS: This was a prospective, randomized, multicenter study in the intensive care units in 10 university hospitals, including 90 adult patients in 2 groups: 55 septic and 35 trauma patients. Patients in each group were randomly divided into 2 subgroups according to the fat emulsions administered (1.4 g/kg per day) as part of the calories for at least 6 days of continuous total parenteral nutrition (TPN). One subgroup was treated with 30% long-chain triglycerides (phospholipid/ triglyceride ratio: 0.04) and the other with 20% long-chain triglycerides (phospholipid/triglyceride ratio: 0.06). The parenteral nutrition formula was isocaloric and isonitrogenous with 0.25 g of nitrogen/kg per day and 40% of the nonprotein calories as fat. Clinical tolerance was assessed during the study. At baseline and after 3 and 6 days of TPN, the following biochemical parameters were measured: prealbumin, retinol-binding protein, serum albumin, hematologic, hepatic and renal function variables, triglycerides, phospholipids, total and free cholesterol, nonesterified cholesterol, nonesterified fatty acids, and lipoproteins. RESULTS: At baseline, no differences in age, gender, severity of the condition [Acute Physiology and Chronic Health Evaluation (APACHE II) score], or clinical chemistry were found between the subgroups. The levels of plasma proteins studied and the renal, hematologic, or hepatic function variables did not vary during the study period. Total cholesterol increased significantly, owing to esterified cholesterol, with 20% long-chain triglyceride in septic patients (baseline: 2.1 +/- 0.8 mmol/L, day 6: 2.8 +/- 0.6 mmol/L, p = .026). In septic patients receiving 20% long-chain triglycerides, plasma triglycerides had a similar behavior (baseline: 1.4 +/- 0.6 mmol/L, day 3: 2.2 +/- 0.8 mmol/L, p < .05). The very-low-density lipoprotein content of cholesterol, triglycerides, and phospholipids showed a tendency to decrease in septic patients treated with 30% long-chain triglycerides (NS). None of the emulsions induced the synthesis of lipoprotein X. CONCLUSIONS: Our results indicate that while both fat emulsions used in the TPN of critically ill patients are clinically safe, the 30% long-chain triglyceride fat emulsion with a phospholipid/triglyceride ratio of 0.04 causes fewer lipid metabolic disturbances.

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.