Mette M. Berger

ESPEN Guidelines on Parenteral Nutrition: Intensive care

Nutritional support in the intensive care setting represents a challenge but it is fortunate that its delivery and monitoring can be followed closely. Enteral feeding guidelines have shown the evidence in favor of early delivery and the efficacy of use of the gastrointestinal tract. Parenteral nutrition (PN) represents an alternative or additional approach when other routes are not succeeding (not necessarily having failed completely) or when it is not possible or would be unsafe to use other routes. The main goal of PN is to deliver a nutrient mixture closely related to requirements safely and to avoid complications. This nutritional approach has been a subject of debate over the past decades. PN carries the considerable risk of overfeeding which can be as deleterious as underfeeding. Therefore the authors will present not only the evidence available regarding the indications for PN, its implementation, the energy required, its possible complementary use with enteral nutrition, but also the relative importance of the macro- and micronutrients in the formula proposed for the critically ill patient. Data on long-term survival (expressed as 6 month survival) will also be considered a relevant outcome measure. Since there is a wide range of interpretations regarding the content of PN and great diversity in its practice, our guidance will necessarily reflect these different views. The papers available are very heterogeneous in quality and methodology (amount of calories, nutrients, proportion of nutrients, patients, etc.) and the different meta-analyses have not always taken this into account. Use of exclusive PN or complementary PN can lead to confusion, calorie targets are rarely achieved, and different nutrients continue to be used in different proportions. The present guidelines are the result of the analysis of the available literature, and acknowledging these limitations, our recommendations are intentionally largely expressed as expert opinions.

Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial

BACKGROUND Enteral nutrition (EN) is recommended for patients in the intensive-care unit (ICU), but it does not consistently achieve nutritional goals. We assessed whether delivery of 100% of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition (SPN) could optimise clinical outcome. METHODS This randomised controlled trial was undertaken in two centres in Switzerland. We enrolled patients on day 3 of admission to the ICU who had received less than 60% of their energy target from EN, were expected to stay for longer than 5 days, and to survive for longer than 7 days. We calculated energy targets with indirect calorimetry on day 3, or if not possible, set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men, respectively. Patients were randomly assigned (1:1) by a computer-generated randomisation sequence to receive EN or SPN. The primary outcome was occurrence of nosocomial infection after cessation of intervention (day 8), measured until end of follow-up (day 28), analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00802503. FINDINGS We randomly assigned 153 patients to SPN and 152 to EN. 30 patients discontinued before the study end. Mean energy delivery between day 4 and 8 was 28 kcal/kg per day (SD 5) for the SPN group (103% [SD 18%] of energy target), compared with 20 kcal/kg per day (7) for the EN group (77% [27%]). Between days 9 and 28, 41 (27%) of 153 patients in the SPN group had a nosocomial infection compared with 58 (38%) of 152 patients in the EN group (hazard ratio 0·65, 95% CI 0·43-0·97; p=0·0338), and the SPN group had a lower mean number of nosocomial infections per patient (-0·42 [-0·79 to -0·05]; p=0·0248). INTERPRETATION Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient. FUNDING Foundation Nutrition 2000Plus, ICU Quality Funds, Baxter, and Fresenius Kabi.

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

ObjectiveCritical 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.MethodsWe 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.ResultsEleven 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.ConclusionsTrace 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.

Antioxidant supplementation in sepsis and systemic inflammatory response syndrome

Objective:Summarize the current knowledge about oxidative stress-related organ dysfunction in inflammatory and septic conditions, and its potential prevention and treatment by antioxidants in critically ill patients, focusing on naturally occurring antioxidants and clinical trials. Study Selection:PubMed, MEDLINE, and personal database search. Synthesis:Plasma concentrations of antioxidant micronutrients are depressed during critical illness and especially during sepsis. The causes of these low levels include losses with biological fluids, low intakes, dilution by resuscitation fluids, as well as systemic inflammatory response syndrome-mediated redistribution of micronutrients from plasma to tissues. Numerous clinical trials have been conducted, many of which have shown beneficial effects of supplementation. Interestingly, among the candidates, glutamine, glutathione, and selenium are linked with the potent glutathione peroxidase enzyme family at some stage of their synthesis and metabolism. Conclusions:Three antioxidant nutrients have demonstrated clinical benefits and reached level A evidence: a) selenium improves clinical outcome (infections, organ failure); b) glutamine reduces infectious complication in large-sized trials; and c) the association of eicosapentaenoic acid and micronutrients has significant anti-inflammatory effects. Other antioxidants are still on the clinical benchmark level, awaiting well-designed clinical trials.

Lactate and glucose metabolism in severe sepsis and cardiogenic shock

Objective:To evaluate the relative importance of increased lactate production as opposed to decreased utilization in hyperlactatemic patients, as well as their relation to glucose metabolism. Design:Prospective observational study. Setting:Surgical intensive care unit of a university hospital. Patients:Seven patients with severe sepsis or septic shock, seven patients with cardiogenic shock, and seven healthy volunteers. Interventions:13C-labeled sodium lactate was infused at 10 &mgr;mol/kg/min and then at 20 &mgr;mol/kg/min over 120 mins each. 2H-labeled glucose was infused throughout. Measurements and Main Results:Baseline arterial lactate was higher in septic (3.2 ± 2.6) and cardiogenic shock patients (2.8 ± 0.4) than in healthy volunteers (0.9 ± 0.20 mmol/L, p < .05). Lactate clearance, computed using pharmacokinetic calculations, was similar in septic, cardiogenic shock, and controls, respectively: 10.8 ± 5.4, 9.6 ± 2.1, and 12.0 ± 2.6 mL/kg/min. Endogenous lactate production was determined as the initial lactate concentration multiplied by lactate clearance. It was markedly enhanced in the patients (septic 26.2 ± 10.5; cardiogenic shock 26.6 ± 5.1) compared with controls (11.2 ± 2.7 &mgr;mol/kg/min, p < .01). 13C-lactate oxidation (septic 54 ± 25; cardiogenic shock 43 ± 16; controls 65 ± 15% of a lactate load of 10 &mgr;mol/kg/min) and transformation of 13C-lactate into 13C-glucose were not different (respectively, 15 ± 15, 9 ± 18, and 10 ± 7%). Endogenous glucose production was markedly increased in the patients (septic 14.8 ± 1.8; cardiogenic shock 15.0 ± 1.5) compared with controls (7.2 ± 1.1 &mgr;mol/kg/min, p < .01) and was not influenced by lactate infusion. Conclusions:In patients suffering from septic or cardiogenic shock, hyperlactatemia was mainly related to increased production, whereas lactate clearance was similar to healthy subjects. Increased lactate production was concomitant to hyperglycemia and increased glucose turnover, suggesting that the latter substantially influences lactate metabolism during critical illness.

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients

IntroductionOxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress.MethodsWe conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 μg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo.ResultsTwo hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 ± 3.2 versus -4.2 ± 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045).ConclusionThe AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation.Trials RegistrationClinical Trials.gov RCT Register: NCT00515736.

Metabolic and nutritional support of critically ill patients: consensus and controversies

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients.

Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials.

IntroductionNosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia.MethodsTwo consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 μg/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20.ResultsThe patients, 42 ± 15 years old, were burned on 46% ± 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 ± 1.2 to 2.0 ± 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023).ConclusionEnhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.

Cutaneous copper and zinc losses in burns

To measure the exudative cutaneous copper (Cu) and zinc (Zn) losses in burns, 10 patients, aged 36 +/- 9 years (mean +/- s.d.) with burns covering 33 +/- 10 per cent of the total body surface area, were studied from the first postburn day (D1) until D7. All intakes and losses were analysed for Cu, Zn and nitrogen (N) content. Cutaneous losses were extracted from textiles surrounding the patients. Urinary excretions were 0.12 +/- 0.06mg/24h for Cu, 0.9 +/- 0.6mg/24h for Zn, and 14.1 +/- 4.4g/24h for N. Mean daily exudative losses through wound seepage from D1 to D7 were 4.7 +/- 2.1mg/24h for Cu, 27.1 +/- 14.4mg/24h for Zn, and 8.7 +/- 3.8g/24h for N. The cumulated mean losses over 7 days were 37mg for Cu, and 212mg for Zn, representing respectively 20-40 per cent and 5-10 per cent of normal body content. Serum Cu and Zn levels were strongly depressed. The urinary Cu/N ratios correlated with clinical improvement. We conclude that the exudative Cu and Zn losses during the first week postburn contribute significantly to the increased nutrient requirements in burns.

ESPEN endorsed recommendations: nutritional therapy in major burns.

BACKGROUND & AIMS Nutrition therapy is a cornerstone of burn care from the early resuscitation phase until the end of rehabilitation. While several aspects of nutrition therapy are similar in major burns and other critical care conditions, the patho-physiology of burn injury with its major endocrine, inflammatory, metabolic and immune alterations requires some specific nutritional interventions. The present text developed by the French speaking societies, is updated to provide evidenced-based recommendations for clinical practice. METHODS A group of burn specialists used the GRADE methodology (Grade of Recommendation, Assessment, Development and Evaluation) to evaluate human burn clinical trials between 1979 and 2011. The resulting recommendations, strong suggestions or suggestions were then rated by the non-burn specialized experts according to their agreement (strong, moderate or weak). RESULTS Eight major recommendations were made. Strong recommendations were made regarding, 1) early enteral feeding, 2) the elevated protein requirements (1.5-2 g/kg in adults, 3 g/kg in children), 3) the limitation of glucose delivery to a maximum of 55% of energy and 5 mg/kg/h associated with moderate blood glucose (target ≤ 8 mmol/l) control by means of continuous infusion, 4) to associated trace element and vitamin substitution early on, and 5) to use non-nutritional strategies to attenuate hypermetabolism by pharmacological (propranolol, oxandrolone) and physical tools (early surgery and thermo-neutral room) during the first weeks after injury. Suggestion were made in absence of indirect calorimetry, to use of the Toronto equation (Schoffield in children) for energy requirement determination (risk of overfeeding), and to maintain fat administration ≤ 30% of total energy delivery. CONCLUSION The nutritional therapy in major burns has evidence-based specificities that contribute to improve clinical outcome.