Explore the vast range of titles available.

Background Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone). Methods In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery. Results In total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p  < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed. Conclusions Provision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated—potentially focusing on the more poorly EN-fed surgical ICU setting. Trial registration NCT01206166

Background Malnutrition in critically ill adults in the intensive care unit (ICU) is associated with a significantly elevated risk of mortality. Adequate nutrition therapy is crucial to optimise outcomes. Currently, there is a paucity of such data in Latin America. Our aims were to characterise current clinical nutrition practices in the ICU setting in Latin America and evaluate whether current practices meet caloric and protein requirements in critically ill patients receiving nutrition therapy. Methods We conducted a cross-sectional, retrospective, observational study in eight Latin American countries (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Panama, and Peru). Eligible patients were critically ill adults hospitalised in the ICU and receiving enteral nutrition (EN) and/or parenteral nutrition (PN) on the Screening Day and the previous day (day −1). Caloric and protein balance on day –1, nutritional status, and prescribed nutrition therapy were recorded. Multivariable logistic regression analysis was performed to identify independent predictors of reaching daily caloric and protein targets. Results The analysis included 1053 patients from 116 hospitals. Evaluation of nutritional status showed that 74.1% of patients had suspected/moderate or severe malnutrition according to the Subjective Global Assessment. Prescribed nutrition therapy included EN alone (79.9%), PN alone (9.4%), and EN + PN (10.7%). Caloric intake met >90% of the daily target in 59.7% of patients on day –1; a caloric deficit was present in 40.3%, with a mean (±SD) daily caloric deficit of –688.8 ± 455.2 kcal. Multivariable logistic regression analysis showed that combined administration of EN + PN was associated with a statistically significant increase in the probability of meeting >90% of daily caloric and protein targets compared with EN alone (odds ratio, 1.56; 95% confidence interval, 1.02–2.39; p  = 0.038). Conclusions In the ICU setting in Latin America, malnutrition was highly prevalent and caloric intake failed to meet targeted energy delivery in 40% of critically ill adults receiving nutrition therapy. Supplemental administration of PN was associated with improved energy and protein delivery; however, PN use was low. Collectively, these findings suggest an opportunity for more effective utilisation of supplemental PN in critically ill adults who fail to receive adequate nutrition from EN alone.

Background As compared to withholding parenteral nutrition (PN) until one week after intensive care unit (ICU) admission, Early PN prolonged ICU dependency in the EPaNIC randomized controlled trial (RCT). The Refeeding RCT showed improved outcome by temporary macronutrient restriction in ICU patients developing refeeding hypophosphatemia, defined as a phosphate decrease of > 0.16 mmol/L to levels < 0.65 mmol/L. We hypothesized that early phosphate changes may identify critically ill patients who are harmed by Early PN, and that dynamic phosphate changes are more discriminative than an absolute threshold for hypophosphatemia. Methods In this secondary analysis of the EPaNIC RCT, we studied whether absolute hypophosphatemia (AHP; < 0.65 mmol/L on the second ICU-day), relative hypophosphatemia (RHP; > 0.16 mmol/L decrease over the first 2 ICU-days), or a combination of both (CHP) interacted with the randomized nutritional strategy for its impact on outcome, adjusted for risk factors. In case of significant interaction, we studied whether the respective change could be predicted by baseline characteristics. Results Of 3520 patients with available phosphate measurements, AHP developed in 9.1%, RHP in 23.7%, and CHP in 5.3% of patients. RHP, but not AHP or CHP, interacted with the randomized intervention for its impact on outcome ( p  = 0.01). In RHP patients, Early PN independently associated with a lower likelihood of an earlier discharge alive from ICU (adjusted HR 0.75 [0.65–0.87]). In patients without RHP, Early PN did not significantly associate with this outcome (adjusted HR 0.93 [0.86–1.00]). Development of RHP was only poorly predicted by admission characteristics (adjusted pseudo R-squared = 1.7%). Conclusion Development of RHP may identify patients who are particularly harmed by early PN. Future studies should prospectively validate the potential of including RHP in a ready-to-feed indicator.

The provision of nutritional support for patients in intensive care units (ICUs) varies widely both within and between institutions. We tested the hypothesis that evidence-based algorithms to improve nutritional support in the ICU would improve patient outcomes. A cluster-randomized controlled trial was performed in the ICUs of 11 community and 3 teaching hospitals between October 1997 and September 1998. Hospital ICUs were stratified by hospital type and randomized to the intervention or control arm. Patients at least 16 years of age with an expected ICU stay of at least 48 hours were enrolled in the study (n = 499). Evidence-based recommendations were introduced in the 7 intervention hospitals by means of in-service education sessions, reminders (local dietitian, posters) and academic detailing that stressed early institution of nutritional support, preferably enteral. Two hospitals crossed over and were excluded from the primary analysis. Compared with the patients in the control hospitals (n = 214), the patients in the intervention hospitals (n = 248) received significantly more days of enteral nutrition (6.7 v. 5.4 per 10 patient-days; p = 0.042), had a significantly shorter mean stay in hospital (25 v. 35 days; p = 0.003) and showed a trend toward reduced mortality (27% v. 37%; p = 0.058). The mean stay in the ICU did not differ between the control and intervention groups (10.9 v. 11.8 days; p = 0.7). Implementation of evidence-based recommendations improved the provision of nutritional support and was associated with improved clinical outcomes.

Undernourishment has been associated with poor outcomes of critical illness in children. The effects of withholding parenteral nutrition (PN) for 1 week in undernourished critically ill children are unknown. To assess the outcome effects of withholding PN for 1 week in undernourished critically ill children. This is a subanalysis of the randomized clinical trial Pediatric Early vs Late Parenteral Nutrition in Intensive Care Unit (PEPaNIC; N = 1440), which focused on the subgroup of pediatric intensive care unit (PICU) patients identified as undernourished on admission. Children included in the PEPaNIC trial were enrolled between June 18, 2012, and July 27, 2015. Undernourishment was defined as weight-for-age z score less than -2 in children younger than 1 year, and body mass index-for-age z score less than -2 in children 1 year or older. Data analysis was conducted from August 3, 2017, to July 6, 2018. Patients were randomized to initiation of supplemental PN within 24 hours (early PN) or after 1 week (late PN) when enteral nutrition was insufficient. Primary end points were risk of new infections acquired in the PICU and time to live PICU discharge, assessed via multivariable logistic regression and Cox proportional hazard analyses, adjusted for risk factors. A total of 289 of 1440 children (20.1%), term newborn to age 17 years, were identified as undernourished, of whom 150 of 717 patients (20.9%) were in the late PN group and 139 of 723 patients (19.2%) were in the early PN group. On admission, characteristics were similar among the treatment groups. Mean (SD) weight z scores were -3.33 (1.18) in the late PN group and -3.21 (1.09) in the early PN group. Compared with well-nourished PICU patients, undernourishment on admission was associated with lower likelihood of an earlier live PICU discharge (adjusted hazard ratio, 0.86; 95% CI, 0.75-0.99; P = .03). Among undernourished PICU patients, late PN reduced the risk of new infections by 11.0% (adjusted odds ratio, 0.39; 95% CI, 0.19-0.78; P = .01), and shortened the duration of PICU stay by a median of 2 days (earlier live PICU discharge: adjusted hazard ratio, 1.37; 95% CI, 1.06-1.75; P = .01). The safety outcomes mortality, incidence of hypoglycemia during the first week, and incidence of weight deterioration during PICU stay were similar between the treatment groups. In undernourished critically ill children, withholding PN for 1 week was clinically superior to early PN. ClinicalTrials.gov Identifier: NCT01536275.

Background The PEPaNIC multicenter randomized controlled trial (RCT) has shown that early administration of supplemental parenteral nutrition (early-PN) as compared with withholding PN for 1 week (late-PN) induced long-term internalizing, externalizing and total emotional/behavioral problems in critically ill children, as observed 4 years later. Early-PN was further shown to alter the methylation status of 37 CpG-sites in leukocyte DNA between admission and discharge from the pediatric intensive care unit (PICU). In a preplanned subanalysis of the PEPaNIC trial, we now investigated whether the altered methylation of these CpG-sites could statistically explain the negative impact of early-PN on emotion/behavior documented 4 years after PICU admission. Results The combination of DNA methylation data and data on behavior 4 years after PICU admission was available for 403 of the 1440 patients (aged 0–17 years at PICU admission) who were included in the PEPaNIC RCT (192 early-PN and 211 late-PN patients). Mediation analyses with use of bootstrapped multivariable non-linear regression analyses adjusted for baseline risk factors revealed that the adverse alterations by early-PN in methylation of the 37 CpG-sites together statistically explained its harmful impact on internalizing, externalizing and total emotional/behavioral problems. When adding the methylation status of the 37 CpG-sites to the models, the explanatory power improved with a 1.710 to 1.851-fold increase, and the impact of the altered methylation status of the CpG-sites explained the impact of the randomization to early-PN versus late-PN. Conclusions Abnormal DNA methylation induced by the early use of PN in the PICU provides a biological basis for its long-term harmful effect on emotion/behavior of critically ill children 4 years after PICU admission. Trial Registration ClinicalTrials.gov NCT01536275, registered February 17, 2012, https://clinicaltrials.gov/ct2/show/NCT01536275 .

Background/Objectives: Recent guidelines for preterm parenteral nutrition (PN) recommend an earlier and higher intake of amino acids (AA) and energy to avoid postnatal catabolism and approximate normal fetal growth. Few investigations explored how early PN may affect electrolyte and water homeostasis. We performed a prospective observational trial to assess the effect of nutrient intake on electrolyte homeostasis and balance. Subjects/Methods: During 16 months, all infants ⩽32 weeks were eligible. In the first week of life, we recorded the following daily: electrolytes (plasma and 8-h urine collection), nutritional intake, urine output, body weight, and we calculated sodium (Na) and potassium (K) balance. Infants were divided, for analysis, into three groups of AA intake: low <1.5 g/kg/day (LAA), medium 1.5–2 g/kg/day (MAA) and high >2 g/kg/day (HAA). Results: A total of 154 infants were included. HAA group presented lower weight loss. Na balance was influenced by urine output and postnatal age, with little contribution of nutrition. Kalemia and K balance were mainly influenced by AA intake. K balance differed among groups: LAA, −2.3 mmol/kg/week; MAA, 1.1 mmol/kg/week; and HAA 2.6 mmol/kg/week ( P <0.0001). In the HAA group, plasma and urine K were significantly lower and non-oliguric hyperkalemia was reduced. Conclusions: Na homeostasis was very slightly modified by early nutrition, suggesting that a negative Na balance is obligatory after birth. We showed that AA intake strongly affects K balance, minimize hyperkalemia and reduces weight loss. As K balance is strictly linked to cellular metabolism, we speculate that early nutrition may inhibit cellular catabolism and reduce the contraction of intracellular water compartment.

Background Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. Methods/design The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient’s health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. Discussion The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. Trial registration ClinicalTrials.gov: NCT03742752 . Registered on 14 November 2018.

The goal of nutrition support is to provide the substrates required to match the bioenergetic needs of the patient and promote the net synthesis of macromolecules required for the preservation of lean mass, organ function, and immunity. Contemporary observational studies have exposed the pervasive undernutrition of critically ill patients and its association with adverse clinical outcomes. The intuitive hypothesis is that optimization of nutrition delivery should improve ICU clinical outcomes. It is therefore surprising that multiple large randomized controlled trials have failed to demonstrate the clinical benefit of restoring or maximizing nutrient intake. This may be in part due to the absence of biological markers that identify patients who are most likely to benefit from nutrition interventions and that monitor the effects of nutrition support. Here, we discuss the need for practical risk stratification tools in critical care nutrition, a proposed rationale for targeted biomarker development, and potential approaches that can be adopted for biomarker identification and validation in the field.

Nutrition therapy during critical illness has been a focus of recent research, with a rapid increase in publications accompanied by two updated international clinical guidelines. However, the translation of evidence into practice is challenging due to the continually evolving, often conflicting trial findings and guideline recommendations. This narrative review aims to provide a comprehensive synthesis and interpretation of the adult critical care nutrition literature, with a particular focus on continuing practice gaps and areas with new data, to assist clinicians in making practical, yet evidence-based decisions regarding nutrition management during the different stages of critical illness.