Proceedings of the 2014 A.S.P.E.N. Research Workshop

The human and earth microbiomes are among the most important biological agents in understanding and preventing disease. Technology is advancing at a fast pace and allowing for high‐resolution analysis of the composition and function of our microbial partners across regions, space, and time. Bioinformaticists and biostatisticians are developing ever more elegant displays to understand the generated megadatasets. A virtual cyberinfrastructure of search engines to cross‐reference the rapidly developing data is emerging in line with technologic advances. Nutrition science will reap the benefits of this new field, and its role in preserving the earth and the humans who inhabit it will become evidently clear. In this report we highlight some of the topics of an A.S.P.E.N.‐sponsored symposium held during Clinical Nutrition Week in 2013 that address the importance of the human microbiome to human health and disease.     

A.S.P.E.N. Clinical Guidelines

Background: Children with severe intestinal failure and prolonged dependence on parenteral nutrition are susceptible to the development of parenteral nutrition–associated liver disease (PNALD). The purpose of this clinical guideline is to develop recommendations for the care of children with PN‐dependent intestinal failure that have the potential to prevent PNALD or improve its treatment. Method: A systematic review of the best available evidence to answer a series of questions regarding clinical management of children with intestinal failure receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. Questions: (1) Is ethanol lock effective in preventing bloodstream infection and catheter removal in children at risk of PNALD? (2) What fat emulsion strategies can be used in pediatric patients with intestinal failure to reduce the risk of or treat PNALD? (3) Can enteral ursodeoxycholic acid improve the treatment of PNALD in pediatric patients with intestinal failure? (4) Are PNALD outcomes improved when patients are managed by a multidisciplinary intestinal rehabilitation team?     

A.S.P.E.N. Clinical Guidelines

Background: Parenteral nutrition (PN) is a high‐alert medication available for patient care within a complex clinical process. Beyond application of best practice recommendations to guide safe use and optimize clinical outcome, several issues are better addressed through evidence‐based policies, procedures, and practices. This document provides evidence‐based guidance for clinical practices involving PN prescribing, order review, and preparation. Method: A systematic review of the best available evidence was used by an expert work group to answer a series of questions about PN prescribing, order review, compounding, labeling, and dispensing. Concepts from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) format were applied as appropriate. The specific clinical guideline recommendations were developed using consensus prior to review and approval by the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. The following questions were addressed: (1) Does education of prescribers improve PN ordering? (2) What is the maximum safe osmolarity of PN admixtures intended for peripheral vein administration? (3) What are the appropriate calcium intake and calcium‐phosphate ratios in PN for optimal neonatal bone mineralization? (4) What are the clinical advantages or disadvantages of commercially available premade (“premixed”) multichambered PN formulations compared with traditional/customized PN formulations? (5) What are the clinical (infection, catheter occlusion) advantages or disadvantages of 2‐in‐1 compared with 3‐in‐1 PN admixtures? (6) What macronutrient dosing limits are expected to provide for the most stable 3‐in‐1 admixtures? (7) What are the most appropriate recommendations for optimizing calcium (gluconate) and (Na‐ or K‐) phosphate compatibility in PN admixtures? (8) What micronutrient contamination is present in parenteral stock solutions currently used to compound PN admixtures? (9) Is it safe to use the PN admixture as a vehicle for non‐nutrient medication delivery? (10) Should heparin be included in the PN admixture to reduce the risk of central vein thrombosis? (11) What methods of repackaging intravenous fat emulsion (IVFE) into smaller patient‐specific volumes are safe? (12) What beyond‐use date should be used for (a) IVFE dispensed for separate infusion in the original container and (b) repackaged IVFE?     

A.S.P.E.N. Clinical Guidelines

Background: Due to the high prevalence of obesity in adults, nutrition support clinicians are encountering greater numbers of obese patients who require nutrition support during hospitalization. The purpose of this clinical guideline is to serve as a framework for the nutrition support care of adult patients with obesity. Method: A systematic review of the best available evidence to answer a series of questions regarding management of nutrition support in patients with obesity was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process, that includes consideration of the strength of the evidence together with the risks and benefits to the patient, was used to develop the clinical guideline recommendations prior to multiple levels of external and internal review and approval by the A.S.P.E.N. Board of Directors. Questions: (1) Do clinical outcomes vary across levels of obesity in critically ill or hospitalized non?intensive care unit (ICU) patients? (2) How should energy requirements be determined in obese critically ill or hospitalized non‐ICU patients? (3) Are clinical outcomes improved with hypocaloric, high protein diets in hospitalized patients? (4) In obese patients who have had a malabsorptive or restrictive surgical procedure, what micronutrients should be evaluated?     

A.S.P.E.N. Clinical Guidelines

Background: Premature infants are at increased risk for metabolic bone disease, with resulting delayed bone growth, osteopenia, and rickets. Method: A systematic review of the best available evidence to answer a series of questions regarding neonatal patients at risk of metabolic bone disease receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the American Society for Parenteral and Enteral Nutrition Board of Directors. Questions: (1) What maternal risk factors predispose the neonate to metabolic bone disease? (2) What is the optimal type of feeding to promote neonatal bone health? (3) When and how should vitamin D supplements be administered? (4) Does parenteral nutrition (PN) predispose a neonate to metabolic bone disease, and if so, are there PN formulation recommendations to minimize this risk?     

A.S.P.E.N. Parenteral Nutrition Safety Consensus Recommendations

Parenteral nutrition (PN) serves as an important therapeutic modality that is used in adults, children, and infants for a variety of indications. The appropriate use of this complex therapy aims to maximize clinical benefit while minimizing the potential risks for adverse events. Complications can occur as a result of the therapy and as the result of the PN process. These consensus recommendations are based on practices that are generally accepted to minimize errors with PN therapy, categorized in the areas of PN prescribing, order review and verification, compounding, and administration. These recommendations should be used in conjunction with other A.S.P.E.N. publications, and researchers should consider studying the questions brought forth in this document.     

A.S.P.E.N. clinical guidelines: nutrition support of neonatal patients at risk for necrotizing enterocolitis

BACKGROUND: Necrotizing enterocolitis (NEC) is one of the most devastating diseases in the neonatal population, with extremely low birth weight and extremely preterm infants at greatest risk. METHOD: A systematic review of the best available evidence to answer a series of questions regarding nutrition support of neonates at risk of NEC was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the A.S.P.E.N. Board of Directors. RESULTS/ CONCLUSIONS: (1) When and how should feeds be started in infants at high risk for NEC? We suggest that minimal enteral nutrition be initiated within the first 2 days of life and advanced by 30 mL/kg/d in infants ≥ 1, 000 g. (Weak) (2) Does the provision of mother's milk reduce the risk of developing NEC? We suggest the exclusive use of mother's milk rather than bovine-based products or formula in infants at risk for NEC. (Weak) (3) Do probiotics reduce the risk of developing NEC? There are insufficient data to recommend the use of probiotics in infants at risk for NEC. (Further research needed.) (4) Do nutrients either prevent or predispose to the development of NEC? We do not recommend glutamine supplementation for infants at risk for NEC (Strong). There is insufficient evidence to recommend arginine and/or long chain polyunsaturated fatty acid supplementation for infants at risk for NEC. (Further research needed.) (5) When should feeds be reintroduced to infants with NEC? There are insufficient data to make a recommendation regarding time to reintroduce feedings to infants after NEC. (Further research needed.).     

Human leukocyte death after a preoperative infusion of medium/long-chain triglyceride and fish oil parenteral emulsions: a randomized study in gastrointestinal cancer patients

Background: Parenteral lipid emulsions (LEs) can influence leukocyte functions. The authors investigated the effect of 2 LEs on leukocyte death in surgical patients with gastrointestinal cancer. Material and Methods: Twenty-five patients from a randomized, double-blind clinical trial (ID: NCT01218841) were randomly included to evaluate leukocyte death after 3 days of preoperative infusion (0.2 g fat/kg/d) of an LE composed equally of medium/long-chain triglycerides and soybean oil (MCTs/LCTs) or pure fish oil (FO). Blood samples were collected before (t0) and after LE infusion (t1) and on the third postoperative day (t2). Results: After LE infusion (t1 vs t0), MCTs/LCTs did not influence cell death; FO slightly increased the proportion of necrotic lymphocytes (5%). At the postoperative period (t2 vs t0), MCTs/LCTs tripled the proportion of apoptotic lymphocytes; FO maintained the slightly increased proportion of necrotic lymphocytes (7%) and reduced the percentage of apoptotic lymphocytes by 74%. In the postoperative period, MCT/LCT emulsion increased the proportion of apoptotic neutrophils, and FO emulsion did not change any parameter of apoptosis in the neutrophil population. There were no differences in lymphocyte or neutrophil death when MCT/LCT and FO treatments were compared during either preoperative or postoperative periods. MCT/LCTs altered the expression of 12 of 108 genes related to cell death, with both pro- and antiapoptotic effects; FO modulated the expression of 7 genes, demonstrating an antiapoptotic effect. Conclusion: In patients with gastrointestinal cancer, preoperative MCT/LCT infusion was associated with postoperative lymphocyte and neutrophil apoptosis. FO has a protective effect on postoperative lymphocyte apoptosis.     

Effect of Critical Illness on Triglyceride Absorption

Background: Adequate nutrition support for critically ill patients optimizes outcome, and enteral feeding is the preferred route of nutrition. Small intestinal glucose absorption is frequently impaired in critical illness. Despite lipid being a major constituent of liquid nutrient administered, there is little information about lipid absorption during critical illness. Objectives: To determine small intestinal lipid, as well as glucose, absorption in critical illness compared with health. Materials and Methods: Twenty‐nine mechanically ventilated critically ill patients and 16 healthy volunteers were studied. Liquid nutrient (60 mL, 1 kcal/mL), containing 200 µL ¹³C‐triolein and 3 g 3‐O‐methyl‐glucose (3‐OMG), was infused directly into the duodenum at a rate of 2 kcal/min. Exhaled ¹³CO₂ and serum 3‐OMG concentrations were measured at timed intervals over 360 minutes. Lipid absorption was measured as the cumulative percentage dose (cPDR) of ¹³CO₂ recovered at 360 minutes. Glucose absorption was measured as the area under the 3‐OMG concentration curve. Data are median (range) and analyzed using the Mann‐Whitney U and Pearson correlation tests. Results: Lipid absorption was markedly less in the critically ill (cPDR¹³CO₂: patients, 22.6% [0%–100%] vs healthy participants, 40.7% [5.3%–84.7%]; P = .018). While glucose absorption was less at 60 minutes in the critically ill (3‐OMG₆₀: 13.2 [3.5–29.5] vs 21.1 [9.3–31.9] mmol/L·min; P = .003), this was not apparent at 360 minutes (3‐OMG₃₆₀: 92.7 [54.5–147.9] vs 107.9 [64.0–168.7] mmol/L·min; P = .126). There was no relationship between lipid and glucose absorption. Conclusion: Small intestinal absorption of lipid is diminished during critical illness.     

Report on the 1986 A.S.P.E.N. Research Workshop on selenium in clinical nutrition

Selenium in human nutrition was the theme of the 1986 Research Workshop of the American Society for Parenteral and Enteral Nutrition. At the workshop, evidence for the nutritional essentiality of selenium to humans was reviewed, and it was concluded that Keshan disease, the cardiomyopathy of children and young women described in China, is now firmly linked to selenium deficiency, although other factors may be involved. Selenium metabolism and techniques for assessing selenium status also received attention at the workshop. A measurement of blood selenium levels was accepted, in general, as a valid technique for assessing selenium status in individuals with relatively constant selenium intakes. Clinical practitioners at the workshop reported that some of their total parenteral nutrition patients not receiving selenium presented biochemical evidence of selenium deficiency, but no characteristic clinical syndrome due to selenium deficiency has yet been observed in such patients. The workshop attendees acknowledged the need for an official guideline for selenium use in total parenteral nutrition, but were unable to develop a consensus regarding such a guideline. However, the workshop agreed that any guideline established in the future should specify the type of patients to be supplemented, the dose of selenium to be administered, and the selenium compound to be used. Until that time, the physician supervising the therapy must assume responsibility both for determining the need for selenium supplementation, and for the administration of the supplemental selenium.     

A.S.P.E.N. Clinical Guidelines

Background: Hyperglycemia is a frequent occurrence in adult hospitalized patients who receive nutrition support. Both hyperglycemia and hypoglycemia (resulting from attempts to correct hyperglycemia) are associated with adverse outcomes in diabetic as well as nondiabetic patients. This American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Clinical Guideline summarizes the most current evidence and provides guidelines for the desired blood glucose goal range in hospitalized patients receiving nutrition support, the definition of hypoglycemia, and the rationale for use of diabetes‐specific enteral formulas in hospitalized patients. Method: A systematic review of the best available evidence to answer a series of questions regarding glucose control in adults receiving parenteral or enteral nutrition was undertaken and evaluated using concepts adopted from the Grading of Recommendations, Assessment, Development and Evaluation working group. A consensus process was used to develop the clinical guideline recommendations prior to external and internal review and approval by the A.S.P.E.N. Board of Directors. Results/Conclusions: 1. What is the desired blood glucose goal range in adult hospitalized patients receiving nutrition support? We recommend a target blood glucose goal range of 140–180 mg/dL (7.8–10 mmol/L). (Strong) 2. How is hypoglycemia defined in adult hospitalized patients receiving nutrition support? We recommend that hypoglycemia be defined as a blood glucose concentration of <70 mg/dL (<3.9 mmol/L). (Strong) 3. Should diabetes‐specific enteral formulas be used for adult hospitalized patients with hyperglycemia? We cannot make a recommendation at this time.     

Characterization of Fatty Acid Profiles in Infants With Intestinal Failure–Associated Liver Disease

Background

The purpose of this study was to characterize fatty acid profiles (FAPs) in parenteral nutrition (PN)‐dependent infants with intestinal failure–associated liver disease (IFALD) receiving soybean oil–based lipid emulsion (SO) doses of ～3 and ～1 g/kg/d.

Methods

Prospectively collected data were retrospectively reviewed. Serum FAPs of patients <1 year old who experienced development of IFALD while receiving standard PN with SO were examined before transitioning to a fish oil–based lipid emulsion for IFALD treatment. Time on SO, dose, gestational age, and weight‐ and length‐for‐age z scores were also reviewed.

Results

Among the 49 patients analyzed, there were no differences in demographics or anthropometrics between patients who received standard SO (SO‐S) (n = 14, range of dosage 2.06–3.31 g/kg/d) and reduced SO (SO‐R) (n = 35, range of dosage 0.90–1.34 g/kg/d). Patients received SO for a median of 53 days (interquartile range 39, 73) before FAP measurement. Patients who received SO‐R had significantly higher Mead acid and lower α‐linolenic, eicosapentaenoic, linoleic, stearic, total ω‐3, and total ω‐6 fatty acid levels than patients who received SO‐S (P < .01). Triene:tetraene ratios were higher in patients who received SO‐R (P = .0009), and no patients experienced biochemical essential fatty acid deficiency (EFAD).

Conclusion

PN‐dependent infants with IFALD receiving SO‐R have different FAPs than patients receiving SO‐S. No patients in either group had biochemical EFAD.