Journal of Parenteral and Enteral Nutrition

Human protein and amino acid nutrition encompasses a wide, complex, frequently misunderstood, and often contentious area of clinical research and practice. This tutorial explains the basic biochemical and physiologic principles that underlie our current understanding of protein and amino acid nutrition. The following topics are discussed: (1) the identity, measurement, and essentiality of nutritional proteins; (2) the definition and determination of minimum requirements; (3) nutrition adaptation; (4) obligatory nitrogen excretion and the minimum protein requirement; (5) minimum versus optimum protein intakes; (6) metabolic responses to surfeit and deficient protein intakes; (7) body composition and protein requirements; (8) labile protein; (9) N balance; (10) the principles of protein and amino acid turnover, including an analysis of the controversial indicator amino acid oxidation technique; (11) general guidelines for evaluating protein turnover articles; (12) amino acid turnover versus clearance; (13) the protein content of hydrated amino acid solutions; (14) protein requirements in special situations, including protein-catabolic critical illness; (15) amino acid supplements and additives, including monosodium glutamate and glutamine; and (16) a perspective on the future of protein and amino acid nutrition research. In addition to providing practical information, this tutorial aims to demonstrate the importance of rigorous physiologic reasoning, stimulate intellectual curiosity, and encourage fresh ideas in this dynamic area of human nutrition. In general, references are provided only for topics that are not well covered in modern textbooks.

Heart failure is a growing public health concern. Advanced heart failure is frequently associated with severe muscle wasting, termed cardiac cachexia. This process is driven by systemic inflammation and tumor necrosis factor in a manner common to other forms of disease-related wasting seen with cancer or human immunodeficiency virus. A variable degree of malnutrition is often superimposed from poor nutrient intake. Cardiac cachexia significantly decreases quality of life and survival in patients with heart failure. This review outlines the evaluation of nutrition status in heart failure, explores the pathophysiology of cardiac cachexia, and discusses therapeutic interventions targeting wasting in these patients.

Background: In hospitals, length of stay (LOS) is a priority but it may be prolonged by malnutrition. This study seeks to determine the contributors to malnutrition at admission and evaluate its effect on LOS. Materials and Methods: This is a prospective cohort study conducted in 18 Canadian hospitals from July 2010 to February 2013 in patients ≥ 18 years admitted for ≥ 2 days. Excluded were those admitted directly to the intensive care unit; obstetric, psychiatry, or palliative wards; or medical day units. At admission, the main nutrition evaluation was subjective global assessment (SGA). Body mass index (BMI) and handgrip strength (HGS) were also performed to assess other aspects of nutrition. Additional information was collected from patients and charts review during hospitalization. Results: One thousand fifteen patients were enrolled: based on SGA, 45% (95% confidence interval [CI], 42%–48%) were malnourished, and based on BMI, 32% (95% CI, 29%–35%) were obese. Independent contributors to malnutrition at admission were Charlson comorbidity index > 2, having 3 diagnostic categories, relying on adult children for grocery shopping, and living alone. The median (range) LOS was 6 (1–117) days. After controlling for demographic, socioeconomic, and disease-related factors and treatment, malnutrition at admission was independently associated with prolonged LOS (hazard ratio, 0.73; 95% CI, 0.62–0.86). Other nutrition-related factors associated with prolonged LOS were lower HGS at admission, receiving nutrition support, and food intake < 50%. Obesity was not a predictor. Conclusion: Malnutrition at admission is prevalent and associated with prolonged LOS. Complex disease and age-related social factors are contributors.

Background: Changes in resting energy expenditure (REE) appear to be one of the causes of nutritional depletion in cancer. Assessing REE may be an important tool for providing adequate nutritional therapy to these patients. The aims of this study were to evaluate REE of patients with gastrointestinal tract cancer and to compare it to that of healthy controls. Methods: A total of 20 patients, with esophageal (n = 3), gastric (n = 9), and colorectal (n = 8) cancers, and 20 healthy subjects were included. Indirect calorimetry (IC) was used to measure REE in both groups. The “pocket” equation (30 kcal/kg) and the Harris-Benedict equation, with correction factors of 1.3 (activity) and 1.1 (injury), were employed for assessment of the estimated total energy expenditure (TEE). Statistics included Mann-Whitney and paired t tests, Bland Altman analysis, and multivariate regression. Results: The REE of the patients (1,274.5 kcal [1,002.9–2,174.9]) was similar to that of the controls (1,445.5 kcal [1,114.5–1,762.6], not significant), even when corrected for the amount of metabolically active tissue. The pocket equation was effective in predicting the patients’ TEE, with a 1.7% (32 kcal) difference being observed in comparison with the IC results corrected with the activity factor (not significant). Conclusions: The patients with digestive tract cancers showed a similar REE to that of the controls. The current formula of 30 kcal/kg is suitable for estimating the TEE of these patients.

Background and Aims: Malnutrition is common in patients with inflammatory bowel disease (IBD) and is associated with poor outcomes. Our aim is to determine if patient self-administered malnutrition screening using the malnutrition universal screening tool (MUST) is reliable by comparing patient scores with those derived from the healthcare practitioner (HCP), the gold standard. Methods: We conducted a prospective validation study at a tertiary Canadian academic center that included 154 adult outpatients with IBD. All patients with IBD completed a self-administered nutrition screening assessment using the MUST score followed by an independent MUST assessment performed by HCPs. The main outcome measure was chance-corrected agreement (κ) of malnutrition risk categorization. Results: For patient-administered MUST, the chance-corrected agreement κ (95% confidence interval [CI]) was 0.83 (0.74–0.92) when comparing low-risk and combined medium- and high-risk patients with HCP screening. Weighted κ analysis comparing all 3 risks groups yielded a κ (95% CI) of 0.85 (0.77–0.93) between patient and HCP screening. All patients were able to screen themselves. Overall, 96% of patients reported the MUST questionnaire as either very easy or easy to understand and to complete. Conclusion: Self-administered nutrition screening in outpatients with IBD is valid using the MUST screening tool and is easy to use. If adopted, this tool will increase utilization of malnutrition screening in hectic outpatient clinic settings and will help HCPs determine which patients require additional nutrition support.

Background: The objective of this study was to revise and improve a questionnaire to assess barriers to providing adequate enteral nutrition (EN) in critically ill adults. Methods: Changes were made to the questionnaire based on feedback from previous respondents. The revised questionnaire, including 20 potential barriers, was pilot tested in 3 hospitals in North America. Nurses were asked to rate each item based on the degree to which it hinders the provision of EN in their intensive care unit (ICU). The acceptability of the revised questionnaire was evaluated using 5 open-ended questions appended at the end of the questionnaire. Results: A total of 81 nurses completed the revised barriers questionnaire. A total of 72 of 73 (99%) respondents felt that the questionnaire was easy to understand, and 64 of 73 (88%) felt that the individual questions were clear. On average, respondents rated the degree to which potential barriers hindered the delivery of EN to the patient as “very little” or “a little.” Statistically significantly differences in mean responses were observed across the 3 ICUs for 8 of the 20 items. The indices of internal reliability were assessed to be acceptable. Conclusions: The revised questionnaire to assess barriers to EN seems acceptable and clinically sensible and now appears to comprehensively list all possible modifiable barriers to delivering EN. This questionnaire needs further study to determine whether measuring barriers with this questionnaire can translate into improved EN delivery to critically ill patients.

Background: The aim of the present study was to elucidate whether the administration of antioxidant-rich nutrients, including branched-chain amino acids (BCAAs), microelements, and vitamins, both alone and in combination, has a positive impact on liver function in a nonalcoholic steatohepatitis (NASH) mouse model and identify the mechanisms underlying these effects. Methods: Seven-week-old male KKAy mice fed a methionine- and choline-deficient diet (MCD) for 4 weeks were divided into 7 groups and fed the following planned diets for another 4 weeks: group A (normal diet), group B (MCD; control), group C (MCD with rich microelements), group D (MCD with rich BCAAs), group E (MCD with rich microelements and BCAAs), and group F (MCD with rich microelements, BCAAs, and vitamins). We then conducted biochemical assays, histological analyses, immunohistochemistry for 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 4-hydroxy-2′-nonenal (4-HNE), and Western blotting for insulin glucose signaling, lipid metabolism, and endoplasmic reticulum (ER) stress–related signaling in liver specimens obtained from mice in each group. Results: The morphometric grades of all NASH-related findings and the mean degree of 8-OHdG immunolocalization in groups D–F were significantly lower than those observed in group B. The expression levels of insulin receptor β subunit (IRβ) and p-elF in groups E and F and those of phosphatidyl-inositol 3 kinase (PI3K85), p-AcelCoA, and PERK in group F were similar to those noted in group A. Conclusions: The administration of a combination of antioxidant-rich nutrients, including BCAAs and microelements, is likely to suppress the progression of NASH by reducing oxidative stress, primarily via the downregulation of the ER stress pathway.

Background. Medical students have historically perceived a lack of training in clinical nutrition. Rapid advances in medical science have compelled significant changes in medical education pedagogy. It is unclear what effect this has had on student’s perceptions. Objective. To assess interns’ perception of clinical nutrition education during medical school. Design. A cross-sectional survey of medical, surgical, and obstetric interns from 6 academic hospitals across the United States during the middle of their first year in November of 2010 (n = 289). Bivariate analysis and logistic regression was used to describe interns’ perceptions and evaluate for factors that determined these perceptions. Results. A total of 122 interns responded to the survey, for a response rate of 42%. These interns represented 72 different medical schools. Only 29% of interns reported they had been sufficiently trained in nutrition. On average, interns who reported being prepared reported a mean of 4 ± 3.4 weeks of training during medical school, while unprepared interns reported a mean of 2 ± 2.6 weeks of training (P = .02). Interns with prior graduate training in nutrition (n = 18) almost exclusively reported that medical school training was insufficient (94%, P = .02). After adjusting for age, gender, internship, undergraduate training, and being a foreign graduate, only the number of weeks of training remained significantly associated with perceived preparation (P = .03). Conclusion. Most interns in medicine, surgery, and obstetrics feel unprepared to handle cases requiring knowledge of clinical nutrition. Interns feel that medical school is not adequately preparing them for the needs of clinical practice.

Background: A new “ready-to-use” triple-chamber container, Numeta (Baxter, Deerfield, IL), is available for preterm parenteral nutrition (PN) to provide nutrients according to the recommendations of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN) Guidelines for Pediatric Parenteral Nutrition. We investigated the clinical application of Numeta compared with individualized PN in preterm infants (≤1.500 g) and evaluated the effects on nutrient intake, costs, and preparation time. Materials and Methods: In a clinical observational study, prescriptions for preterm infants were performed with the new prescription software catoPAN (Cato Software Solutions, Becton Dickinson, Vienna, Austria). Individualized PN and Numeta prescriptions were mirrored, and nutrition content of the PNs was compared with each other and with ESPGHAN/ESPEN recommendations. Furthermore, costs and preparation time were assessed. Results: In total, 374 PN solutions (>1000 g [n = 333]/≤1000 g [n = 41]) were analyzed. Protein intake with Numeta was significantly lower compared with individualized PN and did not meet the recommendations for infants <1500 g during the first day and the period of transition after birth. Energy intake was significantly higher with Numeta. The costs for Numeta preparations were €18 (about US$20) higher than for individualized PN. However, the preparation time/solution was 2 minutes faster with Numeta. Conclusion: Numeta is an alternative to individualized PN for infants >1000 g in the period of stable growth when enteral feedings have already started. Protein intake is significantly lower than in individualized PN solutions. Numeta is more expensive in comparison to individualized PN but saves human resources.

Background: Chylothorax occurs in ~3%–5% of infants undergoing cardiac surgery. Standard treatment requires discontinuation of breast milk feeding, due to the abundance of long-chain triglycerides and transition to a medium-chain triglyceride (MCT)–based formula. Objective: To determine the effectiveness of fat-modified breast milk (MBM) for the treatment of chylothorax compared with MCT formula. Materials and Methods: Infants diagnosed with chylothorax following surgery for congenital heart disease between January 2008 and December 2009 at The Hospital for Sick Children were eligible for this nonrandomized open-label study. Treatment infants (n = 8) received mother’s own milk that had been modified by removing the fat layer via centrifugation and adding MCT, nutrients, and essential fatty acids to provide an estimated 74 kcal/100 mL and 1.4 g/100 mL protein (MBM group). Control infants (n = 8) received an MCT formula (MCT group). The feeding intervention was a minimum of 6 weeks after chest tube removal per The Hospital for Sick Children standard chylothorax treatment protocol. Results: Daily volume and duration of chest tube drainage were not different between the MBM and MCT groups. While there was no statistically significant difference in rates of weight gain (g/d) between feeding groups, infants in the MBM group, who tended to be younger, experienced a decline in mean weight (P = .04) and length (P = .01) for age z scores. Conclusion: Fat-modified breast milk resolved chylothorax; however, strategies to address poor growth need to be developed and evaluated in larger trials prior to widespread clinical adoption of this novel treatment.

Background: Small enteral boluses with human milk may reduce the risk of subsequent feeding intolerance and necrotizing enterocolitis in preterm infants receiving parenteral nutrition (PN). We hypothesized that feeding amniotic fluid, the natural enteral diet of the mammalian fetus, will have similar effects and improve growth and gastrointestinal (GI) maturation in preterm neonates receiving PN, prior to the transition to milk feeding. Materials and Methods: Twenty-seven pigs, delivered by cesarean section at ~90% of gestation, were provided with PN and also fed boluses with amniotic fluid (AF; n = 13, 24–72 mL/kg/d) or no oral supplements (nil per os [NPO]; n = 14) until day 5 when blood, tissue, and fecal samples were collected for analyses. Results: Body weight gain was 2.7-fold higher in AF vs NPO pigs. AF pigs showed slower gastric emptying, reduced meal-induced release of gastric inhibitory peptide and glucagon-like peptide 2, changed gut microbiota, and reduced intestinal permeability. There were no effects on GI weight, percentage mucosa, villus height, plasma citrulline, hexose absorptive capacity, and digestive enzymes. Intestinal interleukin (IL)–1β levels and expression of IL1B and IL8 were increased in AF pigs, while blood biochemistry and amino acid levels were minimally affected. Conclusion: Enteral boluses of AF were well tolerated in the first 5 days of life in preterm pigs receiving PN. Enteral provision of AF before the initiation of milk feeding may stimulate body growth and improve hydration in preterm infants receiving PN. Furthermore, it may improve GI motility and integrity, although most markers of GI maturation remain unchanged.

Introduction: While parenteral nutrition (PN) has revolutionized the management of patients with intestinal failure (IF), central line–associated bloodstream infections (CLABSIs) remain a leading cause of mortality and morbidity in this population. The objective of this study is to characterize the presentation of CLABSIs in pediatric IF and to determine the time to positivity of blood cultures. Methods: A retrospective cohort study of children with IF who presented to our institution for evaluation of a possible CLABSI from January 1, 2012, to December 31, 2012, was performed. Results: Sixty patients with IF were identified. There were 33 cases of CLABSI in 16 patients, with a rate of 1.5 infections per 1000 catheter days. There were no significant differences in age, growth parameters, or catheter days between patients with or without CLABSI. Fever was documented in 85% of patients with CLABSI. These patients demonstrated an increased percentage of neutrophils and higher C-reactive protein levels compared with patients without CLABSI. The mean time to culture positivity was 13.2 hours, and 97% of cultures were positive within 24 hours. Conclusion: Our data suggest that most pediatric patients with IF who have CLABSI develop positive cultures within 24 hours, and the absence of fever and leukocytosis does not necessarily indicate the absence of infection. These findings may support clinical practice guidelines in favor of shorter hospital stay when CLABSI is suspected; however, a prospective analysis of CLABSI in this population is recommended to determine the safety and appropriate setting prior to any practice change.

Background: Temporary enteral access devices (EADs), such as nasogastric (NG), orogastric (OG), and postpyloric (PP), are used in pediatric and neonatal patients to administer nutrition, fluids, and medications. While the use of these temporary EADs is common in pediatric care, it is not known how often these devices are used, what inpatient locations have the highest usage, what size tube is used for a given weight or age of patient, and how placement is verified per hospital policy. Materials and Methods: This was a multicenter 1-day prevalence study. Participating hospitals counted the number of NG, OG, and PP tubes present in their pediatric and neonatal inpatient population. Additional data collected included age, weight and location of the patient, type of hospital, census for that day, and the method(s) used to verify initial tube placement. Results: Of the 63 participating hospitals, there was an overall prevalence of 1991 temporary EADs in a total pediatric and neonatal inpatient census of 8333 children (24% prevalence). There were 1316 NG (66%), 414 were OG (21%), and 261 PP (17%) EADs. The neonatal intensive care unit (NICU) had the highest prevalence (61%), followed by a medical/surgical unit (21%) and pediatric intensive care unit (18%). Verification of EAD placement was reported to be aspiration from the tube (n = 21), auscultation (n = 18), measurement (n = 8), pH (n = 10), and X-ray (n = 6). Conclusion: The use of temporary EADs is common in pediatric care. There is wide variation in how placement of these tubes is verified.

Background: Insertion of nasogastric feeding tubes (NGTs) is common in critical care. However, misplacement is frequent and can carry a significant morbidity. Current methods to confirm position of NGTs are not reliable in this setting. We retrospectively compared the position of NGTs using an electromagnetically guided nasogastric tube (e-NGT) with that demonstrated by chest x-ray (CXR), the proportion of lung placements avoided, and the time taken to establish enteral feeding. Methods: This was a retrospective, observational study undertaken in a tertiary referral, adult intensive care unit between February 2006 and November 2013. Patients were included if they had a radiologically confirmed NGT. All CXRs were independently reviewed by an intensivist to determine position, and a subset of patients had their e-NGT image independently reviewed for quality control. Statistical analysis was in the form of sensitivity and specificity and descriptive where indicated. Results: In total, 121 NGT placements in 113 patients were analyzed. We found a sensitivity of 98% (95% confidence interval [CI], 93.9%–99.7%) and a specificity of 100% (95% CI, 48.0%–100.0%) when using the e-NGT compared with CXR. In the subset of 51 independently reviewed e-NGT images, 9 lung placements were avoided. The mean (SD) time from e-NGT placement to CXR was 185 (264.4) minutes and to feeding was 404 (77.8) minutes. Conclusion: When placed by a dedicated team, e-NGT allowed immediate detection of tube misplacement. As such, if used as the sole method for determining NGT position, e-NGTs minimize feeding delay and the need for multiple CXRs with subsequent cost savings.

Background: Fish oil monotherapy has been an advance for treating intestinal failure–associated liver disease (IFALD). However, such patients are at risk of bleeding complications from liver disease and because fish oil can inhibit thrombosis. We have previously reported abnormal platelet function in neonatal piglets given fish oil monotherapy during parenteral nutrition (PN). The purpose of this study was to determine if abnormal fatty acid composition of the platelets could explain the prior observed antiplatelet effect. Methods: Neonatal piglets were assigned to 2 treatments: PN with fish oil monotherapy (FO; n = 4) or PN with soy oil (SO; n = 5). On day 14, plasma was collected and platelets isolated by centrifuging. The fatty acid content in plasma and platelet plug were measured using gas liquid chromatography and compared with controls (CON; n = 5). Results: The arachidonic acid (AA) content in the FO group was on average half that of the SO group, in both the platelets (FO, 3.5% vs SO, 7.6%; P = .021; CON, 4.5%–11%) and the plasma (FO, 3.8% vs SO, 9.2%; P = .002; CON, 6.1%–9.5%). No bleeding complications were observed for any piglets during PN treatment. Conclusions: Using platelet mapping, we have previously shown that neonatal piglets given fish oil monotherapy have abnormal platelet function in the AA pathway. This report demonstrates that such an abnormality can be explained by platelet AA deficiency. Platelet mapping and platelet fatty acid analysis should be undertaken in human infants treated with fish oil monotherapy during PN.

The shortages of intravenous drugs remains critical, with sterile injectables accounting for 80% of the approximately 300 shortages. The impact is being felt in patients dependent on parenteral nutrition (PN), and severe deficiencies are becoming more commonplace. We report here a man who developed severe zinc deficiency, manifesting as a painful desquamative rash, due to an inability to obtain multi–trace element additives for his PN.